{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T12:38:13Z","timestamp":1794141493114,"version":"4.8.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Defective interfering genes (DIGs) are short viral genomes and interfere with wild-type viral replication. Here, we demonstrate that the new designed SARS-CoV-2 DIG (CD3600) can significantly inhibit the replication of SARS-CoV-2 including Alpha, Delta, Kappa and Omicron variants in human HK-2 cells and influenza DIG (PAD4) can significantly inhibit influenza virus replication in human A549 cells. One dose of influenza DIGs prophylactically protects 90% mice from lethal challenge of A(H1N1)pdm09 virus and CD3600 inhibits SARS-CoV-2 replication in hamster lungs when DIGs are administrated to lungs one day before viral challenge. To further investigate the gene delivery vector in the respiratory tract, a peptidic TAT2-P1&amp;LAH4, which can package genes to form small spherical nanoparticles with high endosomal escape ability, is demonstrated to dramatically increase gene expression in the lung airway. TAT2-P1&amp;LAH4, with the dual-functional TAT2-P1 (gene-delivery and antiviral), can deliver CD3600 to significantly inhibit the replication of Delta and Omicron SARS-CoV-2 in hamster lungs. This peptide-based nanoparticle system can effectively transfect genes in lungs and deliver DIGs to inhibit SARS-CoV-2 variants and influenza virus in vivo, which provides the new insight into the drug delivery system for gene therapy against respiratory viruses.<\/jats:p>","DOI":"10.1038\/s41392-022-01138-0","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T12:03:37Z","timestamp":1659528217000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Peptidic defective interfering gene nanoparticles against Omicron, Delta SARS-CoV-2 variants and influenza A virus in vivo"],"prefix":"10.1038","volume":"7","author":[{"given":"Hanjun","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoiyan","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjie","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man Lung","family":"Yeung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6336-6657","authenticated-orcid":false,"given":"Jasper Fuk-Woo","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1921-5824","authenticated-orcid":false,"given":"Kelvin","family":"Kai-Wang To","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwok-Yung","family":"Yuen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"1138_CR1","unstructured":"Centers for Disease, C. & Prevention Update: drug susceptibility of swine-origin influenza A (H1N1) viruses, April 2009. MMWR Morb Mortal Wkly Rep. 58, 433\u2013435 (2009)."},{"key":"1138_CR2","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1056\/NEJMoa2108891","volume":"385","author":"J Lopez Bernal","year":"2021","unstructured":"Lopez Bernal, J. et al. Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. N. Engl. J. Med 385, 585\u2013594 (2021).","journal-title":"N. Engl. J. Med"},{"key":"1138_CR3","doi-asserted-by":"publisher","first-page":"e0131321","DOI":"10.1128\/JVI.01313-21","volume":"95","author":"A Choi","year":"2021","unstructured":"Choi, A. et al. Serum Neutralizing Activity of mRNA-1273 Against SARS-CoV-2 Variants. J. Virol. 95, e0131321 (2021).","journal-title":"J. Virol"},{"key":"1138_CR4","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1056\/NEJMoa2007764","volume":"383","author":"JH Beigel","year":"2020","unstructured":"Beigel, J. H. et al. Remdesivir for the Treatment of Covid-19 - Final Report. N. Engl. J. Med. 383, 1813\u20131826 (2020).","journal-title":"N. Engl. J. Med."},{"key":"1138_CR5","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1001\/jama.2020.16349","volume":"324","author":"CD Spinner","year":"2020","unstructured":"Spinner, C. D. et al. Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial. Jama 324, 1048\u20131057 (2020).","journal-title":"Jama"},{"key":"1138_CR6","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1080\/14787210.2021.1949984","volume":"20","author":"K Thiruchelvam","year":"2021","unstructured":"Thiruchelvam, K., Kow, C. S., Hadi, M. & Hasan, S. S. The use of remdesivir for the management of patients with moderate-to-severe COVID-19: A systematic review. Expert. Rev. Anti. Infect. Ther. 20, 211\u2013229 (2021).","journal-title":"Expert. Rev. Anti. Infect. Ther"},{"key":"1138_CR7","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/226325a0","volume":"226","author":"AS Huang","year":"1970","unstructured":"Huang, A. S. & Baltimore, D. Defective viral particles and viral disease processes. Nature 226, 325\u2013327 (1970).","journal-title":"Nature"},{"key":"1138_CR8","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s12985-017-0805-6","volume":"14","author":"B Meng","year":"2017","unstructured":"Meng, B. et al. Unexpected complexity in the interference activity of a cloned influenza defective interfering RNA. Virol. J. 14, 138 (2017).","journal-title":"Virol. J."},{"key":"1138_CR9","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1099\/0022-1317-83-2-403","volume":"83","author":"SD Duhaut","year":"2002","unstructured":"Duhaut, S. D. & Dimmock, N. J. Defective segment 1 RNAs that interfere with production of infectious influenza A virus require at least 150 nucleotides of 5\u2019 sequence: evidence from a plasmid-driven system. J. Gen. Virol. 83, 403\u2013411 (2002).","journal-title":"J. Gen. Virol."},{"key":"1138_CR10","doi-asserted-by":"publisher","first-page":"8570","DOI":"10.1128\/JVI.00743-08","volume":"82","author":"NJ Dimmock","year":"2008","unstructured":"Dimmock, N. J., Rainsford, E. W., Scott, P. D. & Marriott, A. C. Influenza virus protecting RNA: an effective prophylactic and therapeutic antiviral. J. Virol. 82, 8570\u20138578 (2008).","journal-title":"J. Virol."},{"key":"1138_CR11","doi-asserted-by":"publisher","first-page":"e0212757","DOI":"10.1371\/journal.pone.0212757","volume":"14","author":"N Bdeir","year":"2019","unstructured":"Bdeir, N. et al. A system for production of defective interfering particles in the absence of infectious influenza A virus. PLoS One 14, e0212757 (2019).","journal-title":"PLoS One"},{"key":"1138_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04792-7","volume":"9","author":"H Zhao","year":"2018","unstructured":"Zhao, H. et al. Dual-functional peptide with defective interfering genes effectively protects mice against avian and seasonal influenza. Nat. Commun. 9, 2358 (2018).","journal-title":"Nat. Commun."},{"key":"1138_CR13","doi-asserted-by":"publisher","first-page":"15300","DOI":"10.1074\/jbc.M401604200","volume":"280","author":"JP Richard","year":"2005","unstructured":"Richard, J. P. et al. Cellular uptake of unconjugated TAT peptide involves clathrin-dependent endocytosis and heparan sulfate receptors. J. Biol. Chem. 280, 15300\u201315306 (2005).","journal-title":"J. Biol. Chem."},{"key":"1138_CR14","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/S1525-0016(03)00122-9","volume":"8","author":"A Ferrari","year":"2003","unstructured":"Ferrari, A. et al. Caveolae-mediated internalization of extracellular HIV-1 tat fusion proteins visualized in real time. Mol. Ther. 8, 284\u2013294 (2003).","journal-title":"Mol. Ther."},{"key":"1138_CR15","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/nm996","volume":"10","author":"JS Wadia","year":"2004","unstructured":"Wadia, J. S., Stan, R. V. & Dowdy, S. F. Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nat. Med. 10, 310\u2013315 (2004).","journal-title":"Nat. Med."},{"key":"1138_CR16","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1111\/j.1600-0854.2007.00572.x","volume":"8","author":"F Duchardt","year":"2007","unstructured":"Duchardt, F., Fotin-Mleczek, M., Schwarz, H., Fischer, R. & Brock, R. A comprehensive model for the cellular uptake of cationic cell-penetrating peptides. Traffic 8, 848\u2013866 (2007).","journal-title":"Traffic"},{"key":"1138_CR17","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1002\/smll.201100001","volume":"7","author":"F Zhao","year":"2011","unstructured":"Zhao, F. et al. Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small 7, 1322\u20131337 (2011).","journal-title":"Small"},{"key":"1138_CR18","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1038\/mt.2016.182","volume":"24","author":"GA Duncan","year":"2016","unstructured":"Duncan, G. A., Jung, J., Hanes, J. & Suk, J. S. The Mucus Barrier to Inhaled Gene Therapy. Mol. Ther. 24, 2043\u20132053 (2016).","journal-title":"Mol. Ther."},{"key":"1138_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/s11671-018-2728-6","volume":"13","author":"P Foroozandeh","year":"2018","unstructured":"Foroozandeh, P. & Aziz, A. A. Insight into Cellular Uptake and Intracellular Trafficking of Nanoparticles. Nanoscale Res Lett. 13, 339 (2018).","journal-title":"Nanoscale Res Lett."},{"key":"1138_CR20","doi-asserted-by":"publisher","first-page":"8720","DOI":"10.1073\/pnas.1502281112","volume":"112","author":"P Mastorakos","year":"2015","unstructured":"Mastorakos, P. et al. Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy. Proc. Natl Acad. Sci. USA 112, 8720\u20138725 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1138_CR21","doi-asserted-by":"publisher","first-page":"2591","DOI":"10.1016\/j.biomaterials.2008.12.076","volume":"30","author":"JS Suk","year":"2009","unstructured":"Suk, J. S. et al. The penetration of fresh undiluted sputum expectorated by cystic fibrosis patients by non-adhesive polymer nanoparticles. Biomaterials 30, 2591\u20132597 (2009).","journal-title":"Biomaterials"},{"key":"1138_CR22","doi-asserted-by":"publisher","first-page":"6022","DOI":"10.1016\/j.cell.2021.11.004","volume":"184","author":"S Chaturvedi","year":"2021","unstructured":"Chaturvedi, S. et al. Identification of a therapeutic interfering particle-A single-dose SARS-CoV-2 antiviral intervention with a high barrier to resistance. Cell 184, 6022\u20136036.e6018 (2021).","journal-title":"Cell"},{"key":"1138_CR23","doi-asserted-by":"publisher","first-page":"5217","DOI":"10.1128\/JVI.03193-13","volume":"88","author":"NJ Dimmock","year":"2014","unstructured":"Dimmock, N. J. & Easton, A. J. Defective interfering influenza virus RNAs: time to reevaluate their clinical potential as broad-spectrum antivirals? J. Virol. 88, 5217\u20135227 (2014).","journal-title":"J. Virol."},{"key":"1138_CR24","first-page":"489","volume":"24","author":"L Qin","year":"2003","unstructured":"Qin, L. et al. Identification of probable genomic packaging signal sequence from SARS-CoV genome by bioinformatics analysis. Acta Pharm. Sin. 24, 489\u2013496 (2003).","journal-title":"Acta Pharm. Sin."},{"key":"1138_CR25","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.virol.2019.08.031","volume":"537","author":"PS Masters","year":"2019","unstructured":"Masters, P. S. Coronavirus genomic RNA packaging. Virology 537, 198\u2013207 (2019).","journal-title":"Virology"},{"key":"1138_CR26","doi-asserted-by":"publisher","first-page":"7890","DOI":"10.1128\/JVI.77.14.7890-7902.2003","volume":"77","author":"D Escors","year":"2003","unstructured":"Escors, D., Izeta, A., Capiscol, C. & Enjuanes, L. Transmissible gastroenteritis coronavirus packaging signal is located at the 5\u2019 end of the virus genome. J. Virol. 77, 7890\u20137902 (2003).","journal-title":"J. Virol."},{"key":"1138_CR27","doi-asserted-by":"publisher","first-page":"5182","DOI":"10.1128\/JVI.00100-13","volume":"87","author":"L Kuo","year":"2013","unstructured":"Kuo, L. & Masters, P. S. Functional analysis of the murine coronavirus genomic RNA packaging signal. J. Virol. 87, 5182\u20135192 (2013).","journal-title":"J. Virol."},{"key":"1138_CR28","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1016\/j.cell.2021.02.053","volume":"184","author":"ML Yeung","year":"2021","unstructured":"Yeung, M. L. et al. Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system. Cell 184, 2212\u20132228.e2212 (2021).","journal-title":"Cell"},{"key":"1138_CR29","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1006\/viro.1998.9267","volume":"248","author":"SD Duhaut","year":"1998","unstructured":"Duhaut, S. D. & Dimmock, N. J. Heterologous protection of mice from a lethal human H1N1 influenza A virus infection by H3N8 equine defective interfering virus: comparison of defective RNA sequences isolated from the DI inoculum and mouse lung. Virology 248, 241\u2013253 (1998).","journal-title":"Virology"},{"key":"1138_CR30","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1099\/0022-1317-83-5-1173","volume":"83","author":"J Park","year":"2002","unstructured":"Park, J. et al. Mutational analysis of a human immunodeficiency virus type 1 Tat protein transduction domain which is required for delivery of an exogenous protein into mammalian cells. J. Gen. Virol. 83, 1173\u20131181 (2002).","journal-title":"J. Gen. Virol."},{"key":"1138_CR31","doi-asserted-by":"publisher","first-page":"16010","DOI":"10.1074\/jbc.272.25.16010","volume":"272","author":"E Vives","year":"1997","unstructured":"Vives, E., Brodin, P. & Lebleu, B. A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. J. Biol. Chem. 272, 16010\u201316017 (1997).","journal-title":"J. Biol. Chem."},{"key":"1138_CR32","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1128\/AAC.01629-10","volume":"55","author":"AN Brown","year":"2011","unstructured":"Brown, A. N. et al. Effect of half-life on the pharmacodynamic index of zanamivir against influenza virus delineated by a mathematical model. Antimicrob. Agents Chemother. 55, 1747\u20131753 (2011).","journal-title":"Antimicrob. Agents Chemother."},{"key":"1138_CR33","doi-asserted-by":"publisher","first-page":"2428","DOI":"10.1093\/cid\/ciaa644","volume":"71","author":"JF Chan","year":"2020","unstructured":"Chan, J. F. et al. Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility. Clin. Infect. Dis. 71, 2428\u20132446 (2020).","journal-title":"Clin. Infect. Dis"},{"key":"1138_CR34","doi-asserted-by":"publisher","first-page":"26955","DOI":"10.1073\/pnas.2014441117","volume":"117","author":"SJF Kaptein","year":"2020","unstructured":"Kaptein, S. J. F. et al. Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity. Proc. Natl Acad. Sci. USA 117, 26955\u201326965 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1138_CR35","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.jconrel.2011.11.024","volume":"158","author":"JK Lam","year":"2012","unstructured":"Lam, J. K. et al. Effective endogenous gene silencing mediated by pH responsive peptides proceeds via multiple pathways. J. Control Release 158, 293\u2013303 (2012).","journal-title":"J. Control Release"},{"key":"1138_CR36","doi-asserted-by":"publisher","first-page":"4110","DOI":"10.1021\/nn9012274","volume":"3","author":"Z Wang","year":"2009","unstructured":"Wang, Z., Tiruppathi, C., Minshall, R. D. & Malik, A. B. Size and dynamics of caveolae studied using nanoparticles in living endothelial cells. ACS Nano 3, 4110\u20134116 (2009).","journal-title":"ACS Nano"},{"key":"1138_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17986-9","volume":"11","author":"H Zhao","year":"2020","unstructured":"Zhao, H. et al. A broad-spectrum virus- and host-targeting peptide against respiratory viruses including influenza virus and SARS-CoV-2. Nat. Commun. 11, 4252 (2020).","journal-title":"Nat. Commun."},{"key":"1138_CR38","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3389\/fmed.2019.00109","volume":"6","author":"N Principi","year":"2019","unstructured":"Principi, N. et al. Drugs for Influenza Treatment: Is There Significant News? Front. Med. 6, 109 (2019).","journal-title":"Front. Med."},{"key":"1138_CR39","doi-asserted-by":"publisher","first-page":"658519","DOI":"10.3389\/fimmu.2021.658519","volume":"12","author":"U Anand","year":"2021","unstructured":"Anand, U. et al. Potential Therapeutic Targets and Vaccine Development for SARS-CoV-2\/COVID-19 Pandemic Management: A Review on the Recent Update. Front. Immunol. 12, 658519 (2021).","journal-title":"Front. Immunol."},{"key":"1138_CR40","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1002\/rmv.641","volume":"20","author":"AC Marriott","year":"2010","unstructured":"Marriott, A. C. & Dimmock, N. J. Defective interfering viruses and their potential as antiviral agents. Rev. Med. Virol. 20, 51\u201362 (2010).","journal-title":"Rev. Med. Virol."},{"key":"1138_CR41","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1186\/1743-422X-8-212","volume":"8","author":"PD Scott","year":"2011","unstructured":"Scott, P. D., Meng, B., Marriott, A. C., Easton, A. J. & Dimmock, N. J. Defective interfering virus protects elderly mice from influenza. Virol. J. 8, 212 (2011).","journal-title":"Virol. J."},{"key":"1138_CR42","doi-asserted-by":"publisher","first-page":"2777","DOI":"10.1016\/j.vaccine.2011.01.102","volume":"29","author":"AJ Easton","year":"2011","unstructured":"Easton, A. J. et al. A novel broad-spectrum treatment for respiratory virus infections: influenza-based defective interfering virus provides protection against pneumovirus infection in vivo. Vaccine 29, 2777\u20132784 (2011).","journal-title":"Vaccine"},{"key":"1138_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21825-w","volume":"12","author":"H Zhao","year":"2021","unstructured":"Zhao, H. et al. Cross-linking peptide and repurposed drugs inhibit both entry pathways of SARS-CoV-2. Nat. Commun. 12, 1517 (2021).","journal-title":"Nat. Commun."},{"key":"1138_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/srep22008","volume":"6","author":"H Zhao","year":"2016","unstructured":"Zhao, H. et al. A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses. Sci. Rep. 6, 22008 (2016).","journal-title":"Sci. Rep."},{"key":"1138_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.virol.2016.08.004","volume":"498","author":"H Zhao","year":"2016","unstructured":"Zhao, H. et al. Novel residues in the PA protein of avian influenza H7N7 virus affect virulence in mammalian hosts. Virology 498, 1\u20138 (2016).","journal-title":"Virology"},{"key":"1138_CR46","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1093\/cid\/ciab656","volume":"74","author":"LL Chen","year":"2021","unstructured":"Chen, L. L. et al. Impact of SARS-CoV-2 variant-associated RBD mutations on the susceptibility to serum antibodies elicited by COVID-19 infection or vaccination. Clin. Infect. Dis. 74, 1623\u20131630 (2021).","journal-title":"Clin. Infect. Dis"},{"key":"1138_CR47","first-page":"1","volume":"11","author":"H Zhao","year":"2021","unstructured":"Zhao, H. et al. SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with delta variant in TMPRSS2-expressed cells. Emerg. Microbes Infect. 11, 1\u201318 (2021).","journal-title":"Emerg. Microbes Infect"},{"key":"1138_CR48","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1080\/22221751.2022.2051753","volume":"11","author":"H Zhao","year":"2022","unstructured":"Zhao, H. et al. Fusion-inhibition peptide broadly inhibits influenza virus and SARS-CoV-2 including Delta and Omicron variants. Emerg. Microbes Infect. 11, 926\u2013937 (2022).","journal-title":"Emerg. Microbes Infect"},{"key":"1138_CR49","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1016\/j.bpj.2022.03.034","volume":"121","author":"I Seim","year":"2021","unstructured":"Seim, I., Roden, C. A. & Gladfelter, A. S. Role of spatial patterning of N-protein interactions in SARS-CoV-2 genome packaging. Biophys. J. 121, 1580 (2021).","journal-title":"Biophys. J"},{"key":"1138_CR50","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1038\/nprot.2007.132","volume":"2","author":"KL Heckman","year":"2007","unstructured":"Heckman, K. L. & Pease, L. R. Gene splicing and mutagenesis by PCR-driven overlap extension. Nat. Protoc. 2, 924\u2013932 (2007).","journal-title":"Nat. Protoc."},{"key":"1138_CR51","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/s41421-022-00428-9","volume":"8","author":"H Zhao","year":"2022","unstructured":"Zhao, H. et al. A trifunctional peptide broadly inhibits SARS-CoV-2 Delta and Omicron variants in hamsters. Cell Disco. 8, 62 (2022).","journal-title":"Cell Disco."},{"key":"1138_CR52","doi-asserted-by":"publisher","first-page":"8091","DOI":"10.1073\/pnas.0711942105","volume":"105","author":"BJ Zheng","year":"2008","unstructured":"Zheng, B. J. et al. Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A\/H5N1 virus. Proc. Natl Acad. Sci. USA 105, 8091\u20138096 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41392-022-01138-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-022-01138-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-022-01138-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T19:07:16Z","timestamp":1669230436000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41392-022-01138-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,3]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["1138"],"URL":"https:\/\/doi.org\/10.1038\/s41392-022-01138-0","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,3]]},"assertion":[{"value":"15 May 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 July 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 August 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"266"}}