{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:46:49Z","timestamp":1790272009656,"version":"4.1.0"},"reference-count":65,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,19]],"date-time":"2025-01-19T00:00:00Z","timestamp":1737244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Center of Drug Design, University of Minnesota"},{"name":"intramural research program of NIDDK"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: p97 (also known as valosin-containing protein, VCP) is a member of the AAA+ ATPase family and is intimately associated with protein quality control and homeostasis regulation. Therefore, pharmaceutical inhibition of p97 has been actively pursued as an anticancer strategy. Recently, p97 has emerged as an important pro-viral host factor and p97 inhibitors are being evaluated as potential antiviral agents. Methods: We designed and synthesized novel p97 inhibitors based on the rearrangement of the central fused ring of our previously reported p97 inhibitors. These compounds were tested for inhibition of p97, cytotoxicity, and antiviral activity against SARS-CoV-2. Molecular docking was also performed on selected inhibitors to shed light on their binding modes. Results: Among these new p97 inhibitors, two compounds possess enhanced anti-p97 activity over their parent compounds. More significantly, these two inhibitors exhibit strong antiviral activity against SARS-CoV-2 at doses with no significant cytotoxicity. Molecular docking reveals no major change of the binding mode relative to that of their parent compounds, further supporting our design strategy. Conclusions: These compounds are structurally novel p97 inhibitors that display low toxicity and possess promising antiviral activity against SARS-CoV-2 and potentially other viruses. Further structural exploration is therefore justified and improved analogs will serve as useful tools for studying p97 as a promising host antiviral target.<\/jats:p>","DOI":"10.3390\/ph18010131","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T04:04:12Z","timestamp":1737345852000},"page":"131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["p97 Inhibitors Possessing Antiviral Activity Against SARS-CoV-2 and Low Cytotoxicity"],"prefix":"10.3390","volume":"18","author":[{"given":"Rui","family":"Ding","sequence":"first","affiliation":[{"name":"Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany C.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9538-3264","authenticated-orcid":false,"given":"Prithwish","family":"Goswami","sequence":"additional","affiliation":[{"name":"Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6624-7001","authenticated-orcid":false,"given":"Christine D.","family":"Dreis","sequence":"additional","affiliation":[{"name":"Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihong","family":"Ye","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0560-6509","authenticated-orcid":false,"given":"Robert J.","family":"Geraghty","sequence":"additional","affiliation":[{"name":"Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4229-863X","authenticated-orcid":false,"given":"Liqiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ye, Y., Tang, W.K., Zhang, T., and Xia, D. (2017). A Mighty \u201cProtein Extractor\u201d of the Cell: Structure and Function of the p97\/CDC48 ATPase. Front. Mol. Biosci., 4.","DOI":"10.3389\/fmolb.2017.00039"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.gene.2016.02.042","article-title":"Structure and function of the AAA+ ATPase p97\/Cdc48p","volume":"583","author":"Xia","year":"2016","journal-title":"Gene"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1016\/j.febslet.2015.08.028","article-title":"Control of p97 function by cofactor binding","volume":"589","author":"Buchberger","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1089\/dna.2014.2452","article-title":"The final moments of misfolded proteins en route to the proteasome","volume":"33","author":"Zhang","year":"2014","journal-title":"DNA Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1091\/mbc.e10-09-0748","article-title":"The AAA-ATPase p97 is essential for outer mitochondrial membrane protein turnover","volume":"22","author":"Xu","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/ncb2407","article-title":"Emerging functions of the VCP\/p97 AAA-ATPase in the ubiquitin system","volume":"14","author":"Meyer","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jsb.2012.03.003","article-title":"Expanding into new markets\u2014VCP\/p97 in endocytosis and autophagy","volume":"179","author":"Bug","year":"2012","journal-title":"J. Struct. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.yexcr.2014.08.025","article-title":"Should I stay or should I go: VCP\/p97-mediated chromatin extraction in the DNA damage response","volume":"329","author":"Dantuma","year":"2014","journal-title":"Exp. Cell Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.canlet.2013.05.030","article-title":"P97\/CDC-48: Proteostasis control in tumor cell biology","volume":"337","author":"Fessart","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"36624","DOI":"10.1074\/jbc.M113.488924","article-title":"Altered intersubunit communication is the molecular basis for functional defects of pathogenic p97 mutants","volume":"288","author":"Tang","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e17834","DOI":"10.7554\/eLife.17834","article-title":"Valosin-containing protein (VCP\/p97) inhibitors relieve Mitofusin-dependent mitochondrial defects due to VCP disease mutants","volume":"6","author":"Zhang","year":"2017","journal-title":"eLife"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"E4380","DOI":"10.1073\/pnas.1706205114","article-title":"Ubiquitin- and ATP-dependent unfoldase activity of P97\/VCP*NPLOC4*UFD1L is enhanced by a mutation that causes multisystem proteinopathy","volume":"114","author":"Blythe","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Das, P., and Dudley, J.P. (2021). How Viruses Use the VCP\/p97 ATPase Molecular Machine. Viruses, 13.","DOI":"10.20944\/preprints202108.0542.v1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.virusres.2016.11.029","article-title":"Valosin-containing protein (VCP\/p97) plays a role in the replication of West Nile virus","volume":"228","author":"Phongphaew","year":"2017","journal-title":"Virus Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e00467-20","DOI":"10.1128\/mBio.00467-20","article-title":"A Sensitive Yellow Fever Virus Entry Reporter Identifies Valosin-Containing Protein (VCP\/p97) as an Essential Host Factor for Flavivirus Uncoating","volume":"11","author":"Ramanathan","year":"2020","journal-title":"mBio"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Anton, A., Mazeaud, C., Freppel, W., Gilbert, C., Tremblay, N., Sow, A.A., Roy, M., Rodrigue-Gervais, I.G., and Chatel-Chaix, L. (2021). Valosin-containing protein ATPase activity regulates the morphogenesis of Zika virus replication organelles and virus-induced cell death. Cell Microbiol., 23.","DOI":"10.1111\/cmi.13302"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.1038\/s41467-021-22966-8","article-title":"Analysis of Zika virus capsid-Aedes aegypti mosquito interactome reveals pro-viral host factors critical for establishing infection","volume":"12","author":"Gestuveo","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e02336-20","DOI":"10.1128\/JVI.02336-20","article-title":"Valosin-containing protein\/p97 plays critical roles in the Japanese encephalitis virus life cycle","volume":"95","author":"Sehrawat","year":"2021","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Arakawa, M., Tabata, K., Ishida, K., Kobayashi, M., Arai, A., Ishikawa, T., Suzuki, R., Takeuchi, H., Tripathi, L.P., and Mizuguchi, K. (2022). Flavivirus recruits the valosin-containing protein-NPL4 complex to induce stress granule disassembly for efficient viral genome replication. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2022.101597"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mazeaud, C., Anton, A., Pahmeier, F., Sow, A.A., Cerikan, B., Freppel, W., Cortese, M., Bartenschlager, R., and Chatel-Chaix, L. (2021). The Biogenesis of Dengue Virus Replication Organelles Requires the ATPase Activity of Valosin-Containing Protein. Viruses, 13.","DOI":"10.3390\/v13102092"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9953","DOI":"10.1128\/JVI.01140-16","article-title":"Affinity Purification of the Hepatitis C Virus Replicase Identifies Valosin-Containing Protein, a Member of the ATPases Associated with Diverse Cellular Activities Family, as an Active Virus Replication Modulator","volume":"90","author":"Yi","year":"2016","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1099\/jgv.0.000828","article-title":"Aggregation of a hepatitis C virus replicase module induced by ablation of p97\/VCP","volume":"98","author":"Yi","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Carissimo, G., Chan, Y.H., Utt, A., Chua, T.K., Bakar, F.A., Merits, A., and Ng, L.F.P. (2019). VCP\/p97 Is a Proviral Host Factor for Replication of Chikungunya Virus and Other Alphaviruses. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.02236"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lin, Y.T., Prendergast, J., and Grey, F. (2017). The host ubiquitin-dependent segregase VCP\/p97 is required for the onset of human cytomegalovirus replication. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006329"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Latorre, V., and Geller, R. (2022). Identification of Cytoplasmic Chaperone Networks Relevant for Respiratory Syncytial Virus Replication. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.880394"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1007\/s00044-020-02679-1","article-title":"Anti-HCMV activity by an irreversible p97 inhibitor LC-1310","volume":"30","author":"Wang","year":"2021","journal-title":"Med. Chem. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.ejps.2019.03.020","article-title":"Identification of NMS-873, an allosteric and specific p97 inhibitor, as a broad antiviral against both influenza A and B viruses","volume":"133","author":"Zhang","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"11116","DOI":"10.1128\/JVI.01360-15","article-title":"Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes","volume":"89","author":"Wong","year":"2015","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/s41586-020-2332-7","article-title":"Proteomics of SARS-CoV-2-infected host cells reveals therapy targets","volume":"583","author":"Bojkova","year":"2020","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Cheng, K.W., Li, S., Wang, F., Ruiz-Lopez, N.M., Houerbi, N., and Chou, T.F. (2021). Impacts of p97 on Proteome Changes in Human Cells during Coronaviral Replication. Cells, 10.","DOI":"10.3390\/cells10112953"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wang, F., Li, S., Cheng, K.W., Rosencrans, W.M., and Chou, T.F. (2022). The p97 Inhibitor UPCDC-30245 Blocks Endo-Lysosomal Degradation. Pharmaceuticals, 15.","DOI":"10.3390\/ph15020204"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1021\/acs.jmedchem.9b01318","article-title":"p97: An Emerging Target for Cancer, Neurodegenerative Diseases, and Viral Infections","volume":"63","author":"Huryn","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"113446","DOI":"10.1016\/j.ejmech.2021.113446","article-title":"AAA ATPases as therapeutic targets: Structure, functions, and small-molecule inhibitors","volume":"219","author":"Zhang","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.chembiol.2022.12.007","article-title":"Inhibitors of the ATPase p97\/VCP: From basic research to clinical applications","volume":"30","author":"Kilgas","year":"2023","journal-title":"Cell Chem. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4834","DOI":"10.1073\/pnas.1015312108","article-title":"Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways","volume":"108","author":"Chou","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/cmdc.201200520","article-title":"Structure-activity relationship study reveals ML240 and ML241 as potent and selective inhibitors of p97 ATPase","volume":"8","author":"Chou","year":"2013","journal-title":"ChemMedChem"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.ccell.2015.10.002","article-title":"Targeting the AAA ATPase p97 as an Approach to Treat Cancer through Disruption of Protein Homeostasis","volume":"28","author":"Anderson","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9480","DOI":"10.1021\/acs.jmedchem.5b01346","article-title":"Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083)","volume":"58","author":"Zhou","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"eabg1168","DOI":"10.1126\/scitranslmed.abg1168","article-title":"Targeting acute myeloid leukemia dependency on VCP-mediated DNA repair through a selective second-generation small-molecule inhibitor","volume":"13","author":"Roux","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, X., Wen, T., Miao, H., Hu, W., Lei, M., and Zhu, Y. (2022). Discovery of a new class of valosine containing protein (VCP\/P97) inhibitors for the treatment of colorectal cancer. Bioorg. Med. Chem., 74.","DOI":"10.1016\/j.bmc.2022.117050"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.bmc.2018.12.036","article-title":"Discovery of a new class of valosine containing protein (VCP\/P97) inhibitors for the treatment of non-small cell lung cancer","volume":"27","author":"Wang","year":"2019","journal-title":"Bioorg. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Xie, X., Wang, X., Wen, T., Zhao, C., Liu, H., Zhao, B., and Zhu, Y. (2021). Discovery of novel pyrimidine molecules containing boronic acid as VCP\/p97 Inhibitors. Bioorg. Med. Chem., 38.","DOI":"10.1016\/j.bmc.2021.116114"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"31784","DOI":"10.1021\/acsomega.0c04478","article-title":"Synthesis and In Vitro Evaluation of 2-[3-(2-Aminoethyl)-1H-indol-1-yl]-N-benzylquinazolin-4-amine as a Novel p97\/VCP Inhibitor Lead Capable of Inducing Apoptosis in Cancer Cells","volume":"5","author":"Feng","year":"2020","journal-title":"ACS Omega"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zhang, X., Jiang, L., Li, Y., Feng, Q., Sun, X., Wang, Y., and Zhao, M. (2023). Discovery of novel benzylquinazoline molecules as p97\/VCP inhibitors. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1209060"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10443","DOI":"10.1021\/jm501313x","article-title":"Discovery of 2-(cyclohexylmethylamino)pyrimidines as a new class of reversible valosine containing protein inhibitors","volume":"57","author":"Cervi","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/nchembio.1313","article-title":"Covalent and allosteric inhibitors of the ATPase VCP\/p97 induce cancer cell death","volume":"9","author":"Magnaghi","year":"2013","journal-title":"Nat. Chem. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1021\/jm3013213","article-title":"Alkylsulfanyl-1,2,4-triazoles, a new class of allosteric valosine containing protein inhibitors. Synthesis and structure-activity relationships","volume":"56","author":"Polucci","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1021\/acsmedchemlett.3c00163","article-title":"Optimization of 1,2,4-Triazole-Based p97 Inhibitors for the Treatment of Cancer","volume":"14","author":"LaPorte","year":"2023","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1126\/science.aad7974","article-title":"2.3 A resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition","volume":"351","author":"Banerjee","year":"2016","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1091\/mbc.e03-07-0506","article-title":"Dissection of the dislocation pathway for type I membrane proteins with a new small molecule inhibitor, eeyarestatin","volume":"15","author":"Fiebiger","year":"2004","journal-title":"Mol. Biol. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Wang, Q., Shinkre, B.A., Lee, J.G., Weniger, M.A., Liu, Y., Chen, W., Wiestner, A., Trenkle, W.C., and Ye, Y. (2010). The ERAD inhibitor Eeyarestatin I is a bifunctional compound with a membrane-binding domain and a p97\/VCP inhibitory group. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015479"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5177","DOI":"10.1016\/j.bmcl.2016.09.068","article-title":"Eeyarestatin I derivatives with improved aqueous solubility","volume":"26","author":"Ding","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7445","DOI":"10.1074\/jbc.M708347200","article-title":"Inhibition of p97-dependent protein degradation by Eeyarestatin I","volume":"283","author":"Wang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"113148","DOI":"10.1016\/j.ejmech.2020.113148","article-title":"A covalent p97\/VCP ATPase inhibitor can overcome resistance to CB-5083 and NMS-873 in colorectal cancer cells","volume":"213","author":"Zhang","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1021\/acs.jmedchem.9b00144","article-title":"Discovery of Irreversible p97 Inhibitors","volume":"62","author":"Ding","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/j.apsb.2021.09.003","article-title":"A targeted covalent inhibitor of p97 with proteome-wide selectivity","volume":"12","author":"Ye","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"115094","DOI":"10.1016\/j.ejmech.2023.115094","article-title":"Synthesis and structure-activity relationships of N-(3-(1H-imidazol-2-yl)phenyl)-3-phenylpropionamide derivatives as a novel class of covalent inhibitors of p97\/VCP ATPase","volume":"248","author":"Wang","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.ejmech.2017.06.019","article-title":"Covalent inhibitors design and discovery","volume":"138","author":"Kurian","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e0086221","DOI":"10.1128\/JVI.00862-21","article-title":"SARS-CoV-2 Disrupts Proximal Elements in the JAK-STAT Pathway","volume":"95","author":"Chen","year":"2021","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1021\/ci500118s","article-title":"Docking covalent inhibitors: A parameter free approach to pose prediction and scoring","volume":"54","author":"Zhu","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1055\/s-0033-1338853","article-title":"Chemoselective Reactions of 4,6-Dichloro-2-(methylsulfonyl)pyrimidine and Related Electrophiles with Amines","volume":"45","author":"Baiazitov","year":"2013","journal-title":"Synth.-Stuttg."},{"key":"ref_62","unstructured":"Raphy, G., Watson, R.J., Hannah, D., Pegurier, C., Ort-Mans, I., Lock, C.J., Knight, R.L., and Owen, D.A. (2008). Novel 2 Amino-Pyrimidine Derivatives, Processes for Preparing Them, Pharmaceutical Compositions Thereof. (2008\/031556 A2), WO Patent."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4685","DOI":"10.1016\/j.bmc.2004.06.024","article-title":"Development of prostaglandin D2 receptor antagonist: Discovery of highly potent antagonists","volume":"12","author":"Torisu","year":"2004","journal-title":"Bioorg. Med. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1021\/acsmedchemlett.2c00265","article-title":"Bisubstrate Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 Nsp14 Methyltransferase","volume":"13","author":"Jung","year":"2022","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Soto-Acosta, R., Edwards, T.C., Dreis, C.D., Krishna, V.D., Cheeran, M.C., Qiu, L., Xie, J., Bonnac, L.F., and Geraghty, R.J. (2021). Enhancing the Antiviral Potency of Nucleobases for Potential Broad-Spectrum Antiviral Therapies. Viruses, 13.","DOI":"10.3390\/v13122508"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/1\/131\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:31:50Z","timestamp":1759919510000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/1\/131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,19]]},"references-count":65,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ph18010131"],"URL":"https:\/\/doi.org\/10.3390\/ph18010131","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,19]]}}}