{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:36:14Z","timestamp":1785411374961,"version":"3.56.0"},"reference-count":200,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X013995\/1"],"award-info":[{"award-number":["MR\/X013995\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"award":["MR\/X013995\/1"],"award-info":[{"award-number":["MR\/X013995\/1"]}],"id":[{"id":"https:\/\/ror.org\/03x94j517","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Although antiviral development against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been dominated by replication-directed strategies, structural and accessory proteins offer a complementary and increasingly important opportunity for small-molecule intervention. These proteins control key processes outside the core replication machinery, including viral entry, membrane remodelling, virion assembly, egress, and host immune modulation, thereby expanding the mechanistic scope of antiviral design. However, many of these targets are membrane-associated, oligomeric, conformationally dynamic, or function through protein\u2013protein interactions, creating distinct challenges in target validation, assay design, and chemical optimisation. In this review, we comprehensively and critically evaluate the structural and accessory proteomes of SARS-CoV-2, with a strict focus on small-molecule tractability and translational relevance. We highlight the most credible direct-acting opportunities, focusing on the membrane (M), envelope (E), and nucleocapsid (N) structural proteins, together with the accessory protein open reading frame 3a (ORF3a), for which emerging chemical matter strengthens confidence in druggability. In contrast, Spike (S) and several host-interface accessory proteins, including ORF6, ORF8, ORF9b, and ORF10, are best viewed as more selective or earlier-stage opportunities that require stronger on-target chemical validation. Emphasis is placed on structural accessibility, mechanism-based assay systems, evidence quality, cellular and in vivo activity, and developability constraints relevant to exposure at the infection site. Rather than replacing replication-directed antivirals, these non-canonical targets are best considered adjunctive or complementary components of future combination strategies designed to broaden antiviral coverage, enhance robustness, and improve pandemic preparedness.<\/jats:p>","DOI":"10.3390\/pharmaceutics18060706","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:43:54Z","timestamp":1780965834000},"page":"706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting SARS-CoV-2 Structural and Accessory Proteins: Emerging Opportunities for Small-Molecule Coronavirus Antivirals"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7463-1468","authenticated-orcid":false,"given":"Exequiel O. J.","family":"Porta","sequence":"first","affiliation":[{"name":"UCL School of Pharmacy, University College London, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana F.","family":"AlKharboush","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London, London WC1N 1AX, UK"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 22252, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Jackson","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Pang","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aylin","family":"Darin","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Louka","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0145-8761","authenticated-orcid":false,"given":"Xinyue","family":"Shi","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"Wells","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6096-9102","authenticated-orcid":false,"given":"Frank","family":"Kozielski","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1016\/j.immuni.2022.09.006","article-title":"SARS-CoV-2 in Immunocompromised Individuals","volume":"55","author":"DeWolf","year":"2022","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mistry, P., Barmania, F., Mellet, J., Peta, K., Strydom, A., Viljoen, I.M., James, W., Gordon, S., and Pepper, M.S. (2022). SARS-CoV-2 Variants, Vaccines, and Host Immunity. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.809244"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jiph.2021.12.014","article-title":"The SARS-CoV-2 Mutations versus Vaccine Effectiveness: New Opportunities to New Challenges","volume":"15","author":"Malik","year":"2022","journal-title":"J. Infect. Public Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa2119451","article-title":"COVID-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant","volume":"386","author":"Andrews","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zabidi, N.Z., Liew, H.L., Farouk, I.A., Puniyamurti, A., Yip, A.J.W., Wijesinghe, V.N., Low, Z.Y., Tang, J.W., Chow, V.T.K., and Lal, S.K. (2023). Evolution of SARS-CoV-2 Variants: Implications on Immune Escape, Vaccination, Therapeutic and Diagnostic Strategies. Viruses, 15.","DOI":"10.3390\/v15040944"},{"key":"ref_6","first-page":"100694","article-title":"Efficacy and Safety of Paxlovid in Severe Adult Patients with SARS-Cov-2 Infection: A Multicenter Randomized Controlled Study","volume":"33","author":"Liu","year":"2023","journal-title":"Lancet Reg. Health\u2013West. Pac."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11779322211025876","DOI":"10.1177\/11779322211025876","article-title":"Structure and Function of Major SARS-CoV-2 and SARS-CoV Proteins","volume":"15","author":"Gorkhali","year":"2021","journal-title":"Bioinform. Biol. Insights"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41392-022-00884-5","article-title":"Structural Biology of SARS-CoV-2: Open the Door for Novel Therapies","volume":"7","author":"Yan","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"165878","DOI":"10.1016\/j.bbadis.2020.165878","article-title":"Insights into SARS-CoV-2 Genome, Structure, Evolution, Pathogenesis and Therapies: Structural Genomics Approach","volume":"1866","author":"Naqvi","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Katiyar, H., Arduini, A., Li, Y., and Liang, C. (2024). SARS-CoV-2 Assembly: Gaining Infectivity and Beyond. Viruses, 16.","DOI":"10.3390\/v16111648"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e2164219","DOI":"10.1080\/22221751.2022.2164219","article-title":"The Role of SARS-CoV-2 Nucleocapsid Protein in Antiviral Immunity and Vaccine Development","volume":"12","author":"Yu","year":"2023","journal-title":"Emerg. Microbes Infect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/s41467-024-44958-0","article-title":"Proteomic Analysis of SARS-CoV-2 Particles Unveils a Key Role of G3BP Proteins in Viral Assembly","volume":"15","author":"Murigneux","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Porta, E.O.J., AlKharboush, D.F., Jackson, L., Pang, F., Darin, A., Louka, J., Quamruzzaman, M., Shi, X., Wells, G., and Kozielski, F. (2026). Targeting SARS-CoV-2 Non-Structural Proteins: A Blueprint for Next-Generation Small-Molecule Coronavirus Antivirals. Pharmaceutics, 18.","DOI":"10.26434\/chemrxiv.15002724\/v1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100111","DOI":"10.1074\/jbc.RA120.016175","article-title":"The SARS-CoV-2 Envelope and Membrane Proteins Modulate Maturation and Retention of the Spike Protein, Allowing Assembly of Virus-like Particles","volume":"296","author":"Boson","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Duan, L., Zheng, Q., Zhang, H., Niu, Y., Lou, Y., and Wang, H. (2020). The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.576622"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e01330-25","DOI":"10.1128\/jvi.01330-25","article-title":"Coronavirus Genome Packaging and Nucleocapsid Assembly","volume":"100","author":"Masters","year":"2026","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e200254","DOI":"10.1590\/0074-02760200254","article-title":"COVID-19: Molecular Targets, Drug Repurposing and New Avenues for Drug Discovery","volume":"115","author":"Senger","year":"2020","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s12964-023-01104-5","article-title":"Structural and Non-Structural Proteins in SARS-CoV-2: Potential Aspects to COVID-19 Treatment or Prevention of Progression of Related Diseases","volume":"21","author":"Kakavandi","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"113889","DOI":"10.1016\/j.biopha.2022.113889","article-title":"The Role of SARS-CoV-2 Accessory Proteins in Immune Evasion","volume":"156","author":"Zandi","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Redondo, N., Zald\u00edvar-L\u00f3pez, S., Garrido, J.J., and Montoya, M. (2021). SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.708264"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1016\/j.molcel.2021.04.008","article-title":"Functional Landscape of SARS-CoV-2 Cellular Restriction","volume":"81","author":"Lewinski","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hagelauer, E., Lotke, R., Kmiec, D., Hu, D., Hohner, M., Stopper, S., Nchioua, R., Kirchhoff, F., Sauter, D., and Schindler, M. (2023). Tetherin Restricts SARS-CoV-2 despite the Presence of Multiple Viral Antagonists. Viruses, 15.","DOI":"10.3390\/v15122364"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.virol.2022.01.003","article-title":"SARS-CoV-2 Viroporin Encoded by ORF3a Triggers the NLRP3 Inflammatory Pathway","volume":"568","author":"Xu","year":"2022","journal-title":"Virology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5376","DOI":"10.1002\/jmv.27050","article-title":"SARS-CoV-2 ORF9b Antagonizes Type I and III Interferons by Targeting Multiple Components of the RIG-I\/MDA-5\u2013MAVS, TLR3\u2013TRIF, and cGAS\u2013STING Signaling Pathways","volume":"93","author":"Han","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/s41423-020-0514-8","article-title":"SARS-CoV-2 Orf9b Suppresses Type I Interferon Responses by Targeting TOM70","volume":"17","author":"Jiang","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"ar62","DOI":"10.1091\/mbc.E23-10-0386","article-title":"SARS-CoV-2 Orf6 Is Positioned in the Nuclear Pore Complex by Rae1 to Inhibit Nucleocytoplasmic Transport","volume":"35","author":"Makio","year":"2024","journal-title":"MBoC"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Li, T., Wen, Y., Guo, H., Yang, T., Yang, H., and Ji, X. (2022). Molecular Mechanism of SARS-CoVs Orf6 Targeting the Rae1\u2013Nup98 Complex to Compete With mRNA Nuclear Export. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.813248"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4782","DOI":"10.1038\/s41467-022-32489-5","article-title":"Structural Basis for Sarbecovirus ORF6 Mediated Blockage of Nucleocytoplasmic Transport","volume":"13","author":"Gao","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2024202118","DOI":"10.1073\/pnas.2024202118","article-title":"The ORF8 Protein of SARS-CoV-2 Mediates Immune Evasion through down-Regulating MHC-\u0399","volume":"118","author":"Zhang","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0140-6736(20)31757-8","article-title":"Effects of a Major Deletion in the SARS-CoV-2 Genome on the Severity of Infection and the Inflammatory Response: An Observational Cohort Study","volume":"396","author":"Young","year":"2020","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Pancer, K., Milewska, A., Owczarek, K., Dabrowska, A., Kowalski, M., \u0141abaj, P.P., Branicki, W., Sanak, M., and Pyrc, K. (2020). The SARS-CoV-2 ORF10 Is Not Essential in Vitro or in Vivo in Humans. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008959"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e2023157118","DOI":"10.1073\/pnas.2023157118","article-title":"ORF10\u2013Cullin-2\u2013ZYG11B Complex Is Not Required for SARS-CoV-2 Infection","volume":"118","author":"Mena","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Minigulov, N., Boranbayev, K., Bekbossynova, A., Gadilgereyeva, B., and Filchakova, O. (2024). Structural Proteins of Human Coronaviruses: What Makes Them Different?. Front. Cell. Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1458383"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.cell.2020.04.011","article-title":"The Architecture of SARS-CoV-2 Transcriptome","volume":"181","author":"Kim","year":"2020","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Rashid, F., Xie, Z., Suleman, M., Shah, A., Khan, S., and Luo, S. (2022). Roles and Functions of SARS-CoV-2 Proteins in Host Immune Evasion. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.940756"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","article-title":"Mechanisms of SARS-CoV-2 Entry into Cells","volume":"23","author":"Jackson","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.abb2507","article-title":"Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation","volume":"367","author":"Wrapp","year":"2020","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41577-020-00480-0","article-title":"Viral Targets for Vaccines against COVID-19","volume":"21","author":"Dai","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100198","DOI":"10.1016\/j.medidd.2024.100198","article-title":"Coronavirus Spike Protein-Based Vaccines. Vaccine Delivery Systems","volume":"24","author":"Asrorov","year":"2024","journal-title":"Med. Drug Discov."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/s41577-021-00542-x","article-title":"Neutralizing Monoclonal Antibodies for Treatment of COVID-19","volume":"21","author":"Taylor","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mittal, A., Khattri, A., and Verma, V. (2022). Structural and antigenic variations in the spike protein of emerging SARS-CoV-2 variants. PLoS Pathog., 18.","DOI":"10.1371\/journal.ppat.1010260"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5496","DOI":"10.1038\/s41467-024-49656-5","article-title":"A Broadly Generalizable Stabilization Strategy for Sarbecovirus Fusion Machinery Vaccines","volume":"15","author":"Lee","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein","volume":"181","author":"Walls","year":"2020","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1126\/science.abb9983","article-title":"Site-Specific Glycan Analysis of the SARS-CoV-2 Spike","volume":"369","author":"Watanabe","year":"2020","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Crawford, K.H.D., Eguia, R., Dingens, A.S., Loes, A.N., Malone, K.D., Wolf, C.R., Chu, H.Y., Tortorici, M.A., Veesler, D., and Murphy, M. (2020). Protocol and Reagents for Pseudotyping Lentiviral Particles with SARS-CoV-2 Spike Protein for Neutralization Assays. Viruses, 12.","DOI":"10.1101\/2020.04.20.051219"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1126\/science.abd3255","article-title":"Free Fatty Acid Binding Pocket in the Locked Structure of SARS-CoV-2 Spike Protein","volume":"370","author":"Toelzer","year":"2020","journal-title":"Science"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/s41577-022-00784-3","article-title":"Broadly Neutralizing Antibodies to SARS-CoV-2 and Other Human Coronaviruses","volume":"23","author":"Chen","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.immuni.2023.02.005","article-title":"Broadly Neutralizing Anti-S2 Antibodies Protect against All Three Human Betacoronaviruses That Cause Deadly Disease","volume":"56","author":"Zhou","year":"2023","journal-title":"Immunity"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1056\/NEJMoa2107934","article-title":"Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab","volume":"385","author":"Gupta","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.ccm.2022.11.008","article-title":"Antiviral Treatment of Coronavirus Disease-2019 Pneumonia","volume":"44","author":"Radcliffe","year":"2023","journal-title":"Clin. Chest Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"105949","DOI":"10.1016\/j.antiviral.2024.105949","article-title":"Molecules Targeting a Novel Homotrimer Cavity of Spike Protein Attenuate Replication of SARS-CoV-2","volume":"228","author":"Daniels","year":"2024","journal-title":"Antivir. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"100144","DOI":"10.1016\/j.cellin.2023.100144","article-title":"Development of SARS-CoV-2 Entry Antivirals","volume":"3","author":"Dong","year":"2024","journal-title":"Cell Insight"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.cmi.2024.01.029","article-title":"TMPRSS2 Inhibitors for the Treatment of COVID-19 in Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials of Nafamostat and Camostat Mesylate","volume":"30","author":"Morpeth","year":"2024","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"EVIDoa2300132","DOI":"10.1056\/EVIDoa2300132","article-title":"A Randomized Trial of Nafamostat for COVID-19","volume":"2","author":"Morpeth","year":"2023","journal-title":"NEJM Evid."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41422-020-0305-x","article-title":"Inhibition of SARS-CoV-2 (Previously 2019-nCoV) Infection by a Highly Potent Pan-Coronavirus Fusion Inhibitor Targeting Its Spike Protein That Harbors a High Capacity to Mediate Membrane Fusion","volume":"30","author":"Xia","year":"2020","journal-title":"Cell Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1016\/j.apsb.2021.07.026","article-title":"A Highly Potent and Stable Pan-Coronavirus Fusion Inhibitor as a Candidate Prophylactic and Therapeutic for COVID-19 and Other Coronavirus Diseases","volume":"12","author":"Zhou","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"17928","DOI":"10.1002\/chem.202103258","article-title":"Metallodrug Profiling against SARS-CoV-2 Target Proteins Identifies Highly Potent Inhibitors of the S\/ACE2 Interaction and the Papain-like Protease PLpro","volume":"27","author":"Basu","year":"2021","journal-title":"Chem. Eur. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15140","DOI":"10.1002\/chem.202004112","article-title":"Gold Metallodrugs to Target Coronavirus Proteins: Inhibitory Effects on the Spike-ACE2 Interaction and on PLpro Protease Activity by Auranofin and Gold Organometallics**","volume":"26","author":"Basu","year":"2020","journal-title":"Chem. Eur. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1126\/science.abd9909","article-title":"De Novo Design of Picomolar SARS-CoV-2 Miniprotein Inhibitors","volume":"370","author":"Cao","year":"2020","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.chom.2021.06.008","article-title":"Ultrapotent Miniproteins Targeting the SARS-CoV-2 Receptor-Binding Domain Protect against Infection and Disease","volume":"29","author":"Case","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/s41586-022-04661-w","article-title":"A TMPRSS2 Inhibitor Acts as a Pan-SARS-CoV-2 Prophylactic and Therapeutic","volume":"605","author":"Shapira","year":"2022","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/s41392-022-01084-x","article-title":"TMPRSS2, a Novel Host-Directed Drug Target against SARS-CoV-2","volume":"7","author":"Keller","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.chom.2021.02.003","article-title":"Comprehensive Mapping of Mutations in the SARS-CoV-2 Receptor-Binding Domain That Affect Recognition by Polyclonal Human Plasma Antibodies","volume":"29","author":"Greaney","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4196","DOI":"10.1038\/s41467-021-24435-8","article-title":"Mapping Mutations to the SARS-CoV-2 RBD That Escape Binding by Different Classes of Antibodies","volume":"12","author":"Greaney","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1016\/j.cell.2021.03.028","article-title":"N-Terminal Domain Antigenic Mapping Reveals a Site of Vulnerability for SARS-CoV-2","volume":"184","author":"McCallum","year":"2021","journal-title":"Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/s41586-021-03291-y","article-title":"SARS-CoV-2 Evolution during Treatment of Chronic Infection","volume":"592","author":"Kemp","year":"2021","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6405","DOI":"10.1038\/s41467-021-26602-3","article-title":"Within-Host Evolution of SARS-CoV-2 in an Immunosuppressed COVID-19 Patient as a Source of Immune Escape Variants","volume":"12","author":"Weigang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/s41579-021-00573-0","article-title":"SARS-CoV-2 Variants, Spike Mutations and Immune Escape","volume":"19","author":"Harvey","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_70","first-page":"162","article-title":"SARS-CoV-2 Variant Biology: Immune Escape, Transmission and Fitness","volume":"21","author":"Carabelli","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"110428","DOI":"10.1016\/j.celrep.2022.110428","article-title":"Cryo-EM Structure of the SARS-CoV-2 Omicron Spike","volume":"38","author":"Cerutti","year":"2022","journal-title":"Cell Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/j.cell.2020.08.012","article-title":"Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding","volume":"182","author":"Starr","year":"2020","journal-title":"Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41586-022-04474-x","article-title":"Altered TMPRSS2 Usage by SARS-CoV-2 Omicron Impacts Infectivity and Fusogenicity","volume":"603","author":"Meng","year":"2022","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/s41586-021-04386-2","article-title":"Broadly Neutralizing Antibodies Overcome SARS-CoV-2 Omicron Antigenic Shift","volume":"602","author":"Cameroni","year":"2022","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1126\/science.abj3321","article-title":"Broad Betacoronavirus Neutralization by a Stem Helix-Specific Human Antibody","volume":"373","author":"Pinto","year":"2021","journal-title":"Science"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"103856","DOI":"10.1016\/j.ebiom.2022.103856","article-title":"Randomised Controlled Trial of Intravenous Nafamostat Mesylate in COVID Pneumonitis: Phase 1b\/2a Experimental Study to Investigate Safety, Pharmacokinetics and Pharmacodynamics","volume":"76","author":"Quinn","year":"2022","journal-title":"eBioMedicine"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e00452-22","DOI":"10.1128\/aac.00452-22","article-title":"A Double-Blind, Randomized, Placebo-Controlled, Phase II Clinical Study To Evaluate the Efficacy and Safety of Camostat Mesylate (DWJ1248) in Adult Patients with Mild to Moderate COVID-19","volume":"67","author":"Kim","year":"2023","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41421-020-0169-8","article-title":"The Anti-Influenza Virus Drug, Arbidol Is an Efficient Inhibitor of SARS-CoV-2 In Vitro","volume":"6","author":"Wang","year":"2020","journal-title":"Cell Discov."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/s41594-020-00536-8","article-title":"Structure and Drug Binding of the SARS-CoV-2 Envelope Protein Transmembrane Domain in Lipid Bilayers","volume":"27","author":"Mandala","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1021\/acs.biochem.2c00464","article-title":"The SARS-CoV-2 Envelope Protein Forms Clustered Pentamers in Lipid Bilayers","volume":"61","author":"Somberg","year":"2022","journal-title":"Biochemistry"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3390\/v4030363","article-title":"The Coronavirus E Protein: Assembly and Beyond","volume":"4","author":"Ruch","year":"2012","journal-title":"Viruses"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.virol.2015.08.010","article-title":"Severe Acute Respiratory Syndrome Coronavirus E Protein Transports Calcium Ions and Activates the NLRP3 Inflammasome","volume":"485","author":"Torres","year":"2015","journal-title":"Virology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3870","DOI":"10.1128\/JVI.03566-14","article-title":"Severe Acute Respiratory Syndrome Coronaviruses with Mutations in the E Protein Are Attenuated and Promising Vaccine Candidates","volume":"89","author":"Fett","year":"2015","journal-title":"J. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1128\/JVI.01467-06","article-title":"A Severe Acute Respiratory Syndrome Coronavirus That Lacks the E Gene Is Attenuated in Vitro and in Vivo","volume":"81","author":"DeDiego","year":"2007","journal-title":"J. Virol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5794","DOI":"10.1128\/JVI.00060-11","article-title":"Identification of a Golgi Complex-Targeting Signal in the Cytoplasmic Tail of the Severe Acute Respiratory Syndrome Coronavirus Envelope Protein","volume":"85","author":"Cohen","year":"2011","journal-title":"J. Virol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.virol.2006.05.028","article-title":"Hexamethylene Amiloride Blocks E Protein Ion Channels and Inhibits Coronavirus Replication","volume":"353","author":"Wilson","year":"2006","journal-title":"Virology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1038\/s42003-021-02866-9","article-title":"Amantadine Inhibits Known and Novel Ion Channels Encoded by SARS-CoV-2 in Vitro","volume":"4","author":"Jeppesen","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.bbrc.2020.05.206","article-title":"SARS-CoV-2 E Protein Is a Potential Ion Channel That Can Be Inhibited by Gliclazide and Memantine","volume":"530","author":"Arkin","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ijbiomac.2021.02.011","article-title":"Targeting C-Terminal Helical Bundle of NCOVID19 Envelope (E) Protein","volume":"175","author":"Mukherjee","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"100233","DOI":"10.1016\/j.crphar.2025.100233","article-title":"Fragment-Based Drug Discovery: A Graphical Review","volume":"9","author":"AlKharboush","year":"2025","journal-title":"Curr. Res. Pharmacol. Drug Discov."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Ewart, G., Bobardt, M., Bentzen, B.H., Yan, Y., Thomson, A., Klumpp, K., Becker, S., Rosenkilde, M.M., Miller, M., and Gallay, P. (2023). Post-Infection Treatment with the E Protein Inhibitor BIT225 Reduces Disease Severity and Increases Survival of K18-hACE2 Transgenic Mice Infected with a Lethal Dose of SARS-CoV-2. PLoS Pathog., 19.","DOI":"10.1101\/2023.03.29.534854"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e4755","DOI":"10.1002\/pro.4755","article-title":"Hexamethylene Amiloride Binds the SARS-CoV-2 Envelope Protein at the Protein-Lipid Interface","volume":"32","author":"Somberg","year":"2023","journal-title":"Protein Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1093\/infdis\/jiaa635","article-title":"Human Immunodeficiency Virus Type 1 Vpu Inhibitor, BIT225, in Combination with 3-Drug Antiretroviral Therapy: Inflammation and Immune Cell Modulation","volume":"223","author":"Luscombe","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.3390\/covid2110111","article-title":"Anti-SARS-CoV-2 Activity of Adamantanes In Vitro and in Animal Models of Infection","volume":"2","author":"Lim","year":"2022","journal-title":"COVID"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Yu, H.-G., Sizemore, G., Martinez, I., and Perrotta, P. (2022). Inhibition of SARS-CoV-2 Viral Channel Activity Using FDA-Approved Channel Modulators Independent of Variants. Biomolecules, 12.","DOI":"10.3390\/biom12111673"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Gammeltoft, K.A., Galli, A., Offersgaard, A., Fahn\u00f8e, U., Ramirez, S., Bukh, J., and Gottwein, J.M. (2021). Efficacy of Ion-Channel Inhibitors Amantadine, Memantine and Rimantadine for the Treatment of SARS-CoV-2 In Vitro. Viruses, 13.","DOI":"10.3390\/v13102082"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e81702","DOI":"10.7554\/eLife.81702","article-title":"Structure of SARS-CoV-2 M Protein in Lipid Nanodiscs","volume":"11","author":"Dolan","year":"2022","journal-title":"eLife"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4399","DOI":"10.1038\/s41467-022-32019-3","article-title":"Structure of SARS-CoV-2 Membrane Protein Essential for Virus Assembly","volume":"13","author":"Zhang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e0103624","DOI":"10.1128\/jvi.01036-24","article-title":"SARS-CoV-2 N Protein Coordinates Viral Particle Assembly through Multiple Domains","volume":"98","author":"Han","year":"2024","journal-title":"J. Virol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41392-020-00438-7","article-title":"Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Membrane (M) Protein Inhibits Type I and III Interferon Production by Targeting RIG-I\/MDA-5 Signaling","volume":"5","author":"Zheng","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Sui, L., Zhao, Y., Wang, W., Wu, P., Wang, Z., Yu, Y., Hou, Z., Tan, G., and Liu, Q. (2021). SARS-CoV-2 Membrane Protein Inhibits Type I Interferon Production Through Ubiquitin-Mediated Degradation of TBK1. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.662989"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"6647","DOI":"10.1093\/nar\/gkae256","article-title":"Assembly of SARS-CoV-2 Nucleocapsid Protein with Nucleic Acid","volume":"52","author":"Zhao","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"110285","DOI":"10.1016\/j.virol.2024.110285","article-title":"Strengths and Limitations of SARS-CoV-2 Virus-like Particle Systems","volume":"601","author":"Sultana","year":"2025","journal-title":"Virology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"11318","DOI":"10.1128\/JVI.01052-08","article-title":"The M, E, and N Structural Proteins of the Severe Acute Respiratory Syndrome Coronavirus Are Required for Efficient Assembly, Trafficking, and Release of Virus-Like Particles","volume":"82","author":"Siu","year":"2008","journal-title":"J. Virol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4357","DOI":"10.1128\/JVI.03212-15","article-title":"Analyses of Coronavirus Assembly Interactions with Interspecies Membrane and Nucleocapsid Protein Chimeras","volume":"90","author":"Kuo","year":"2016","journal-title":"J. Virol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/s41586-025-08651-6","article-title":"A Small-Molecule SARS-CoV-2 Inhibitor Targeting the Membrane Protein","volume":"640","author":"Abeywickrema","year":"2025","journal-title":"Nature"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/s41586-025-08773-x","article-title":"A Coronavirus Assembly Inhibitor That Targets the Viral Membrane Protein","volume":"640","author":"Laporte","year":"2025","journal-title":"Nature"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.apsb.2020.04.009","article-title":"Crystal Structure of SARS-CoV-2 Nucleocapsid Protein RNA Binding Domain Reveals Potential Unique Drug Targeting Sites","volume":"10","author":"Kang","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e106478","DOI":"10.15252\/embj.2020106478","article-title":"SARS-CoV-2 Nucleocapsid Protein Phase-Separates with RNA and with Human hnRNPs","volume":"39","author":"Perdikari","year":"2020","journal-title":"EMBO J."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"100260","DOI":"10.1016\/j.jbc.2021.100260","article-title":"1,6-Hexanediol, Commonly Used to Dissolve Liquid\u2013Liquid Phase Separated Condensates, Directly Impairs Kinase and Phosphatase Activities","volume":"296","author":"Kaltheuner","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"107879","DOI":"10.1016\/j.jsb.2022.107879","article-title":"Structural Basis for SARS-CoV-2 Nucleocapsid (N) Protein Recognition by 14-3-3 Proteins","volume":"214","author":"Eisenreichova","year":"2022","journal-title":"J. Struct. Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"167891","DOI":"10.1016\/j.jmb.2022.167891","article-title":"Human 14-3-3 Proteins Site-Selectively Bind the Mutational Hotspot Region of SARS-CoV-2 Nucleoprotein Modulating Its Phosphoregulation","volume":"435","author":"Tugaeva","year":"2023","journal-title":"J. Mol. Biol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Dinesh, D.C., Chalupska, D., Silhan, J., Koutna, E., Nencka, R., Veverka, V., and Boura, E. (2020). Structural Basis of RNA Recognition by the SARS-CoV-2 Nucleocapsid Phosphoprotein. PLoS Pathog., 16.","DOI":"10.1101\/2020.04.02.022194"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"pgad333","DOI":"10.1093\/pnasnexus\/pgad333","article-title":"RNA Structure and Multiple Weak Interactions Balance the Interplay between RNA Binding and Phase Separation of SARS-CoV-2 Nucleocapsid","volume":"2","author":"Estelle","year":"2023","journal-title":"PNAS Nexus"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41392-021-00575-7","article-title":"RNA-Induced Liquid Phase Separation of SARS-CoV-2 Nucleocapsid Protein Facilitates NF-\u03baB Hyper-Activation and Inflammation","volume":"6","author":"Wu","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.molcel.2020.11.041","article-title":"Genomic RNA Elements Drive Phase Separation of the SARS-CoV-2 Nucleocapsid","volume":"80","author":"Iserman","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"18500","DOI":"10.1038\/s41598-022-22576-4","article-title":"Discovery and Structural Characterization of Chicoric Acid as a SARS-CoV-2 Nucleocapsid Protein Ligand and RNA Binding Disruptor","volume":"12","author":"Mercaldi","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1002\/1873-3468.14229","article-title":"SARS-CoV-2 Nucleocapsid Protein Interacts with Immunoregulators and Stress Granules and Phase Separates to Form Liquid Droplets","volume":"595","author":"Somasekharan","year":"2021","journal-title":"FEBS Lett."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s10593-021-02920-8","article-title":"Modeling the Binding of Protoporphyrin IX, Verteporfin, and Chlorin E6 to SARS-CoV-2 Proteins","volume":"57","author":"Koifman","year":"2021","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Huang, Y., Chen, J., Chen, S., Huang, C., Li, B., Li, J., Jin, Z., Zhang, Q., Pan, P., and Du, W. (2024). Molecular Characterization of SARS-CoV-2 Nucleocapsid Protein. Front. Cell. Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1415885"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1016\/j.scib.2022.10.021","article-title":"Antiviral Drug Design Based on Structural Insights into the N-Terminal Domain and C-Terminal Domain of the SARS-CoV-2 Nucleocapsid Protein","volume":"67","author":"Luan","year":"2022","journal-title":"Sci. Bull."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1093\/jb\/mvad008","article-title":"Inhibition of SARS-CoV-2 Nucleocapsid Protein\u2013RNA Interaction by Guanosine Oligomeric RNA","volume":"173","author":"Sekine","year":"2023","journal-title":"J. Biochem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.3724\/abbs.2023106","article-title":"Small Molecules in Regulating Protein Phase Separation","volume":"55","author":"Li","year":"2023","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"101677","DOI":"10.1016\/j.jbc.2022.101677","article-title":"Phase Separation by the SARS-CoV-2 Nucleocapsid Protein: Consensus and Open Questions","volume":"298","author":"Cascarina","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12985-023-01968-6","article-title":"The SARS-CoV-2 Nucleocapsid Protein: Its Role in the Viral Life Cycle, Structure and Functions, and Use as a Potential Target in the Development of Vaccines and Diagnostics","volume":"20","author":"Wu","year":"2023","journal-title":"Virol. J."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.bpj.2024.01.013","article-title":"Targeting Protein-Protein Interaction Interfaces with Antiviral N Protein Inhibitor in SARS-CoV-2","volume":"123","author":"Hong","year":"2024","journal-title":"Biophys. J."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Guo, C., Xu, H., Li, X., Yu, J., and Lin, D. (2023). Suramin Disturbs the Association of the N-Terminal Domain of SARS-CoV-2 Nucleocapsid Protein with RNA. Molecules, 28.","DOI":"10.3390\/molecules28062534"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/s41392-021-00568-6","article-title":"An Integrative Drug Repositioning Framework Discovered a Potential Therapeutic Agent Targeting COVID-19","volume":"6","author":"Ge","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Ayll\u00f3n, B.D., De Lucas-Rius, A., Mendoza-Garc\u00eda, L., Garc\u00eda-Garc\u00eda, T., Fern\u00e1ndez-Rodr\u00edguez, R., Su\u00e1rez-C\u00e1rdenas, J.M., Santos, F.M., Corrales, F., Redondo, N., and Pedrucci, F. (2023). SARS-CoV-2 Accessory Proteins Involvement in Inflammatory and Profibrotic Processes through IL11 Signaling. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1220306"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/s41586-021-03610-3","article-title":"SARS-CoV-2 Uses a Multipronged Strategy to Impede Host Protein Synthesis","volume":"594","author":"Finkel","year":"2021","journal-title":"Nature"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.virol.2021.02.013","article-title":"Conflicting and Ambiguous Names of Overlapping ORFs in the SARS-CoV-2 Genome: A Homology-Based Resolution","volume":"558","author":"Jungreis","year":"2021","journal-title":"Virology"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"109124","DOI":"10.1016\/j.abb.2022.109124","article-title":"The Importance of Accessory Protein Variants in the Pathogenicity of SARS-CoV-2","volume":"717","author":"Hassan","year":"2022","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"108080","DOI":"10.1016\/j.isci.2023.108080","article-title":"The SARS-CoV-2 Protein ORF3c Is a Mitochondrial Modulator of Innate Immunity","volume":"26","author":"Stewart","year":"2023","journal-title":"iScience"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/s41594-021-00619-0","article-title":"Cryo-EM Structure of SARS-CoV-2 ORF3a in Lipid Nanodiscs","volume":"28","author":"Kern","year":"2021","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/s41420-024-01966-9","article-title":"SARS-CoV-2 and Its ORF3a, E and M Viroporins Activate Inflammasome in Human Macrophages and Induce of IL-1\u03b1 in Pulmonary Epithelial and Endothelial Cells","volume":"10","author":"Kozlowski","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1038\/s41467-024-46417-2","article-title":"SARS-CoV-2 Virulence Factor ORF3a Blocks Lysosome Function by Modulating TBC1D5-Dependent Rab7 GTPase Cycle","volume":"15","author":"Walia","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1080\/15548627.2022.2116677","article-title":"Subversion of Autophagy Machinery and Organelle-Specific Autophagy by SARS-CoV-2 and Coronaviruses","volume":"19","author":"Sun","year":"2023","journal-title":"Autophagy"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"4337","DOI":"10.1038\/s41467-022-31930-z","article-title":"A Live-Attenuated SARS-CoV-2 Vaccine Candidate with Accessory Protein Deletions","volume":"13","author":"Liu","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"e00402-21","DOI":"10.1128\/JVI.00402-21","article-title":"Contribution of SARS-CoV-2 Accessory Proteins to Viral Pathogenicity in K18 Human ACE2 Transgenic Mice","volume":"95","author":"Silvas","year":"2021","journal-title":"J. Virol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s42003-024-07442-5","article-title":"SARS-CoV-2 ORF3a Accessory Protein Is a Water-Permeable Channel That Induces Lysosome Swelling","volume":"8","author":"Michelucci","year":"2025","journal-title":"Commun. Biol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"e84477","DOI":"10.7554\/eLife.84477","article-title":"The SARS-CoV-2 Accessory Protein Orf3a Is Not an Ion Channel, but Does Interact with Trafficking Proteins","volume":"12","author":"Miller","year":"2023","journal-title":"eLife"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.antiviral.2011.02.008","article-title":"Emodin Inhibits Current through SARS-Associated Coronavirus 3a Protein","volume":"90","author":"Schwarz","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"5328","DOI":"10.1038\/s41598-023-31764-9","article-title":"Channel Activity of SARS-CoV-2 Viroporin ORF3a Inhibited by Adamantanes and Phenolic Plant Metabolites","volume":"13","author":"Fam","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Garrett, T.J., Coatsworth, H., Mahmud, I., Hamerly, T., Stephenson, C.J., Ayers, J.B., Yazd, H.S., Miller, M.R., Lednicky, J.A., and Dinglasan, R.R. (2023). Niclosamide as a Chemical Probe for Analyzing SARS-CoV-2 Modulation of Host Cell Lipid Metabolism. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1251065"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1080\/22221751.2021.1872353","article-title":"The Interplay between Emerging Human Coronavirus Infections and Autophagy","volume":"10","author":"Zhao","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"ref_146","unstructured":"Tufts Medical Center (2025, October 07). Niclosamide for Patients with Mild to Moderate Disease from Novel Coronavirus (COVID-19); Clinical trial Registration NCT04399356; clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04399356."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Cesar-Silva, D., Pereira-Dutra, F.S., Moraes Giannini, A.L., and Jacques G. de Almeida, C. (2022). The Endolysosomal System: The Acid Test for SARS-CoV-2. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094576"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.ijbiomac.2020.12.142","article-title":"SARS-Cov-2 ORF3a: Mutability and Function","volume":"170","author":"Bianchi","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"109765","DOI":"10.1016\/j.mehy.2020.109765","article-title":"Plausible Mechanisms of Niclosamide as an Antiviral Agent against COVID-19","volume":"140","author":"Pindiprolu","year":"2020","journal-title":"Med. Hypotheses"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"e00065-21","DOI":"10.1128\/mBio.00065-21","article-title":"SARS-CoV-2 ORF6 Disrupts Bidirectional Nucleocytoplasmic Transport through Interactions with Rae1 and Nup98","volume":"12","author":"Addetia","year":"2021","journal-title":"mBio"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"28344","DOI":"10.1073\/pnas.2016650117","article-title":"SARS-CoV-2 Orf6 Hijacks Nup98 to Block STAT Nuclear Import and Antagonize Interferon Signaling","volume":"117","author":"Miorin","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"e01194-23","DOI":"10.1128\/mbio.01194-23","article-title":"SARS-CoV-2 ORF6 Protein Does Not Antagonize Interferon Signaling in Respiratory Epithelial Calu-3 Cells during Infection","volume":"14","author":"Li","year":"2023","journal-title":"mBio"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"e2307997121","DOI":"10.1073\/pnas.2307997121","article-title":"Quantitative Comparison of Nuclear Transport Inhibition by SARS Coronavirus ORF6 Reveals the Importance of Oligomerization","volume":"121","author":"Yoo","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"17668","DOI":"10.1021\/jacs.4c17030","article-title":"NMR Structural Characterization of SARS-CoV-2 ORF6 Reveals an N-Terminal Membrane Anchor","volume":"147","author":"Razmazma","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Mostafa-Hedeab, G., Al-kuraishy, H.M., Al-Gareeb, A.I., Welson, N.N., El-Saber Batiha, G., and Conte-Junior, C.A. (2022). Selinexor and COVID-19: The Neglected Warden. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.884228"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Krachmarova, E., Petkov, P., Lilkova, E., Stoynova, D., Malinova, K., Hristova, R., Gospodinov, A., Ilieva, N., Nacheva, G., and Litov, L. (2024). Interferon-\u03b3 as a Potential Inhibitor of SARS-CoV-2 ORF6 Accessory Protein. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042155"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/22221751.2021.1872351","article-title":"Characterization of SARS-CoV-2 ORF6 Deletion Variants Detected in a Nosocomial Cluster during Routine Genomic Surveillance, Lyon, France","volume":"10","author":"Destras","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/s42003-022-03427-4","article-title":"SARS-CoV-2 ORF6 Disrupts Nucleocytoplasmic Trafficking to Advance Viral Replication","volume":"5","author":"Miyamoto","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"105115","DOI":"10.1016\/j.antiviral.2021.105115","article-title":"Selinexor, a Novel Selective Inhibitor of Nuclear Export, Reduces SARS-CoV-2 Infection and Protects the Respiratory System in Vivo","volume":"192","author":"Kashyap","year":"2021","journal-title":"Antivir. Res."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"101724","DOI":"10.1016\/j.jbc.2022.101724","article-title":"SARS-CoV-2 Accessory Protein ORF8 Is Secreted Extracellularly as a Glycoprotein Homodimer","volume":"298","author":"Matsuoka","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"e2021785118","DOI":"10.1073\/pnas.2021785118","article-title":"Structure of SARS-CoV-2 ORF8, a Rapidly Evolving Immune Evasion Protein","volume":"118","author":"Flower","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"e01610-20","DOI":"10.1128\/mBio.01610-20","article-title":"Discovery and Genomic Characterization of a 382-Nucleotide Deletion in ORF7b and ORF8 during the Early Evolution of SARS-CoV-2","volume":"11","author":"Su","year":"2020","journal-title":"mBio"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Mohammad, S., Bouchama, A., Mohammad Alharbi, B., Rashid, M., Saleem Khatlani, T., Gaber, N.S., and Malik, S.S. (2020). SARS-CoV-2 ORF8 and SARS-CoV ORF8ab: Genomic Divergence and Functional Convergence. Pathogens, 9.","DOI":"10.20944\/preprints202007.0587.v1"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"e2221652120","DOI":"10.1073\/pnas.2221652120","article-title":"Enhanced Inhibition of MHC-I Expression by SARS-CoV-2 Omicron Subvariants","volume":"120","author":"Moriyama","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"102293","DOI":"10.1016\/j.isci.2021.102293","article-title":"ORF8 Contributes to Cytokine Storm during SARS-CoV-2 Infection by Activating IL-17 Pathway","volume":"24","author":"Lin","year":"2021","journal-title":"iScience"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"e00402-22","DOI":"10.1128\/mbio.00402-22","article-title":"Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8","volume":"13","author":"Wu","year":"2022","journal-title":"mBio"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"106929","DOI":"10.1016\/j.isci.2023.106929","article-title":"Secreted ORF8 Induces Monocytic Pro-Inflammatory Cytokines through NLRP3 Pathways in Patients with Severe COVID-19","volume":"26","author":"Wu","year":"2023","journal-title":"iScience"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Arduini, A., Laprise, F., and Liang, C. (2023). SARS-CoV-2 ORF8: A Rapidly Evolving Immune and Viral Modulator in COVID-19. Viruses, 15.","DOI":"10.3390\/v15040871"},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Chen, X., Zhou, Z., Huang, C., Zhou, Z., Kang, S., Huang, Z., Jiang, G., Hong, Z., Chen, Q., and Yang, M. (2021). Crystal Structures of Bat and Human Coronavirus ORF8 Protein Ig-Like Domain Provide Insights Into the Diversity of Immune Responses. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.807134"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"mjad062","DOI":"10.1093\/jmcb\/mjad062","article-title":"The Unique ORF8 Protein from SARS-CoV-2 Binds to Human Dendritic Cells and Induces a Hyper-Inflammatory Cytokine Storm","volume":"15","author":"Hamdorf","year":"2023","journal-title":"J. Mol. Cell Biol."},{"key":"ref_171","first-page":"2884","article-title":"Monocyte Response to SARS-CoV-2 Protein ORF8 Is Associated with Severe COVID-19 Infection in Patients with Chronic Lymphocytic Leukemia","volume":"109","author":"Ruan","year":"2024","journal-title":"Haematologica"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"16814","DOI":"10.1038\/s41598-021-96110-3","article-title":"SARS-CoV-2 Infection Initiates Interleukin-17-Enriched Transcriptional Response in Different Cells from Multiple Organs","volume":"11","author":"Hasan","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Vinjamuri, S., Li, L., and Bouvier, M. (2022). SARS-CoV-2 ORF8: One Protein, Seemingly One Structure, and Many Functions. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1035559"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1007\/s10875-021-01142-z","article-title":"Robust Virus-Specific Adaptive Immunity in COVID-19 Patients with SARS-CoV-2 \u0394382 Variant Infection","volume":"42","author":"Fong","year":"2022","journal-title":"J. Clin. Immunol."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Padilla-Blanco, M., Garc\u00eda-Garc\u00eda, T., Grigas, J., L\u00f3pez-Ayll\u00f3n, B.D., Garrido, J.J., Oliva, M.A., and Montoya, M. (2025). Hidden Players of COVID-19: The Evolving Roles of SARS-CoV-2 Accessory Proteins. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1726698"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1038\/s41467-021-23118-8","article-title":"Crystal Structure of SARS-CoV-2 Orf9b in Complex with Human TOM70 Suggests Unusual Virus-Host Interactions","volume":"12","author":"Gao","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Brandherm, L., Koba\u0161, A.M., Kl\u00f6hn, M., Br\u00fcggemann, Y., Pfaender, S., Rassow, J., and Kreimendahl, S. (2021). Phosphorylation of SARS-CoV-2 Orf9b Regulates Its Targeting to Two Binding Sites in TOM70 and Recruitment of Hsp90. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179233"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/s41586-021-04352-y","article-title":"Evolution of Enhanced Innate Immune Evasion by SARS-CoV-2","volume":"602","author":"Thorne","year":"2022","journal-title":"Nature"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/j.str.2006.05.012","article-title":"The Crystal Structure of ORF-9b, a Lipid Binding Protein from the SARS Coronavirus","volume":"14","author":"Meier","year":"2006","journal-title":"Structure"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s11427-022-2168-8","article-title":"Structural Characterization of SARS-CoV-2 Dimeric ORF9b Reveals Potential Fold-Switching Trigger Mechanism","volume":"66","author":"Jin","year":"2023","journal-title":"Sci. China Life Sci."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"RP106484","DOI":"10.7554\/eLife.106484","article-title":"Coupled Equilibria of Dimerization and Lipid Binding Modulate SARS Cov 2 Orf9b Interactions and Interferon Response","volume":"14","author":"Batra","year":"2025","journal-title":"eLife"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1007\/s13205-024-04032-4","article-title":"In Silico Screening and Evaluation of Antiviral Peptides as Inhibitors against ORF9b Protein of SARS-CoV-2","volume":"14","author":"Sharma","year":"2024","journal-title":"3 Biotech."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"e70145","DOI":"10.1002\/jmv.70145","article-title":"Induction of the Inflammasome by the SARS-CoV-2 Accessory Protein ORF9b, Abrogated by Small-Molecule ORF9b Homodimerization Inhibitors","volume":"97","author":"Zodda","year":"2025","journal-title":"J. Med. Virol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1083\/jcb.201708044","article-title":"Tom70 Enhances Mitochondrial Preprotein Import Efficiency by Binding to Internal Targeting Sequences","volume":"217","author":"Backes","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"4164","DOI":"10.1016\/j.apsb.2024.05.018","article-title":"SARS-CoV-2 ORF10 Hijacking Ubiquitination Machinery Reveals Potential Unique Drug Targeting Sites","volume":"14","author":"Zhu","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"e202108015","DOI":"10.1083\/jcb.202108015","article-title":"SARS-CoV-2 ORF10 Impairs Cilia by Enhancing CUL2ZYG11B Activity","volume":"221","author":"Wang","year":"2022","journal-title":"J. Cell Biol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bbrc.2022.05.069","article-title":"Structural Insights into ORF10 Recognition by ZYG11B","volume":"616","author":"Zhang","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41423-021-00807-4","article-title":"SARS-CoV-2 ORF10 Suppresses the Antiviral Innate Immune Response by Degrading MAVS through Mitophagy","volume":"19","author":"Li","year":"2022","journal-title":"Cell. Mol. Immunol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/s42003-022-03669-2","article-title":"How Many SARS-CoV-2 \u201cViroporins\u201d Are Really Ion Channels?","volume":"5","author":"Harrison","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/s41420-022-01115-0","article-title":"Neddylation Tunes Peripheral Blood Mononuclear Cells Immune Response in COVID-19 Patients","volume":"8","author":"Iruzubieta","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Smith, A., and Dong, X. (2026). BST-2 Inhibits SARS-CoV-2 Egress at Intracellular Membranes and Is Neutralized by ORF7a. Sci. Rep.","DOI":"10.1038\/s41598-026-53209-9"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"e109","DOI":"10.24072\/pcjournal.496","article-title":"Re-Annotation of SARS-CoV-2 Proteins Using an HHpred-Based Approach Opens New Opportunities for a Better Understanding of This Virus","volume":"4","year":"2024","journal-title":"Peer Community J."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/s41577-022-00715-2","article-title":"ORF9c and ORF10 as Accessory Proteins of SARS-CoV-2 in Immune Evasion","volume":"22","author":"Zandi","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Zhang, J., Hom, K., Zhang, C., Nasr, M., Gerzanich, V., Zhang, Y., Tang, Q., Xue, F., Simard, J.M., and Zhao, R.Y. (2024). SARS-CoV-2 ORF3a Protein as a Therapeutic Target against COVID-19 and Long-Term Post-Infection Effects. Pathogens, 13.","DOI":"10.3390\/pathogens13010075"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"106185","DOI":"10.1016\/j.biocel.2022.106185","article-title":"Viroporins: Structure, Function, and Their Role in the Life Cycle of SARS-CoV-2","volume":"145","author":"Breitinger","year":"2022","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1021\/acscentsci.2c01190","article-title":"In Silico Discovery of Small Molecule Modulators Targeting the Achilles\u2019 Heel of SARS-CoV-2 Spike Protein","volume":"9","author":"Wang","year":"2023","journal-title":"ACS Cent. Sci."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"28779","DOI":"10.1021\/acsomega.2c00844","article-title":"Small Molecules Targeting SARS-CoV-2 Spike Glycoprotein Receptor-Binding Domain","volume":"7","author":"Cardoze","year":"2022","journal-title":"ACS Omega"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"12256","DOI":"10.1021\/acs.jmedchem.0c00502","article-title":"Inhibitors of SARS-CoV-2 Entry: Current and Future Opportunities","volume":"63","author":"Xiu","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Karczmarzyk, K., and K\u0119sik-Brodacka, M. (2026). Challenges and Prospects in the Development of a Universal SARS-CoV-2 Vaccine. Vaccines, 14.","DOI":"10.3390\/vaccines14020173"},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Schiavina, M., Pontoriero, L., Tagliaferro, G., Pierattelli, R., and Felli, I.C. (2022). The Role of Disordered Regions in Orchestrating the Properties of Multidomain Proteins: The SARS-CoV-2 Nucleocapsid Protein and Its Interaction with Enoxaparin. Biomolecules, 12.","DOI":"10.3390\/biom12091302"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/6\/706\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:12:33Z","timestamp":1781323953000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/6\/706"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,8]]},"references-count":200,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["pharmaceutics18060706"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18060706","relation":{"has-preprint":[{"id-type":"doi","id":"10.26434\/chemrxiv.15002710\/v1","asserted-by":"object"}]},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,8]]}}}