{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T19:34:16Z","timestamp":1793388856771,"version":"4.5.0"},"reference-count":147,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"738","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,3,13]]},"abstract":"<jats:p>\n                    Inhibitors of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M\n                    <jats:sup>pro<\/jats:sup>\n                    ) such as nirmatrelvir (NTV) and ensitrelvir (ETV) have proven effective in reducing the severity of COVID-19, but the presence of resistance-conferring mutations in sequenced viral genomes raises concerns about future drug resistance. Second-generation oral drugs that retain function against these mutants are thus urgently needed. We hypothesized that the covalent hepatitis C virus protease inhibitor boceprevir (BPV) could serve as the basis for orally bioavailable drugs that inhibit SARS-CoV-2 M\n                    <jats:sup>pro<\/jats:sup>\n                    more efficiently than existing drugs. Performing structure-guided modifications of BPV, we developed a picomolar-affinity inhibitor, ML2006a4, with antiviral activity, oral pharmacokinetics, and therapeutic efficacy similar or superior to those of NTV. A crucial feature of ML2006a4 is a derivatization of the ketoamide reactive group that improves cell permeability and oral bioavailability. Last, ML2006a4 was found to be less sensitive to several mutations that cause resistance to NTV or ETV and occur in the natural SARS-CoV-2 population. Thus, anticipatory design can preemptively address potential resistance mechanisms to expand future treatment options against coronavirus variants.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adi0979","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T13:59:03Z","timestamp":1710338343000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":49,"title":["An orally bioavailable SARS-CoV-2 main protease inhibitor exhibits improved affinity and reduced sensitivity to mutations"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2312-5282","authenticated-orcid":true,"given":"Michael","family":"Westberg","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark."},{"name":"Interdisciplinary Nanoscience Center (iNANO), Aarhus University, 8000 Aarhus C, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5715-835X","authenticated-orcid":true,"given":"Yichi","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Stanford University, Stanford, CA 94305, USA."},{"name":"Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3382-2401","authenticated-orcid":true,"given":"Xinzhi","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2460-0695","authenticated-orcid":true,"given":"Pinghan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6921-1012","authenticated-orcid":true,"given":"Arjun","family":"Rustagi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1657-8320","authenticated-orcid":true,"given":"Jaishree","family":"Garhyan","sequence":"additional","affiliation":[{"name":"Stanford In Vitro Biosafety Level 3 Service Center, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puja Bhavesh","family":"Patel","sequence":"additional","affiliation":[{"name":"Stanford In Vitro Biosafety Level 3 Service Center, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6221-152X","authenticated-orcid":true,"given":"Daniel","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Program in Chemistry, Engineering, and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA 94305, USA."},{"name":"Sarafan ChEM-H, Macromolecular Structure Knowledge Center, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2596-1943","authenticated-orcid":true,"given":"Yan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6803-7270","authenticated-orcid":true,"given":"Chenzhou","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieh-Wen","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0990-3962","authenticated-orcid":true,"given":"Marwah","family":"Karim","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee","family":"Beck","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9598-7255","authenticated-orcid":true,"given":"Panatda","family":"Saenkham-Huntsinger","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0274-3900","authenticated-orcid":true,"given":"Vivian","family":"Tat","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0201-5017","authenticated-orcid":true,"given":"Aleksandra","family":"Drelich","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1323-2241","authenticated-orcid":true,"given":"Bi-Hung","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch, Galveston, TX 77555, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6441-4171","authenticated-orcid":true,"given":"Shirit","family":"Einav","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA."},{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5726-9834","authenticated-orcid":true,"given":"Chien-Te K.","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA."},{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA."},{"name":"Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch, Galveston, TX 77555, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6946-7627","authenticated-orcid":true,"given":"Catherine","family":"Blish","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0492-1961","authenticated-orcid":true,"given":"Michael Z.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Bioengineering, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"WHO \u201cCOVID-19 Weekly Epidemiological Update - 29 September 2023\u201d (2023)."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7112e1"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00462-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01528-14"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2020.127377"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01348-12"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03688-14"},{"key":"e_1_3_2_9_2","first-page":"1","article-title":"Reversal of the progression of fatal coronavirus infection in cats by a broad-spectrum coronavirus protease inhibitor","volume":"12","author":"Kim Y.","year":"2016","unstructured":"Y. Kim, H. Liu, A. C. Galasiti Kankanamalage, S. Weerasekara, D. H. Hua, W. C. Groutas, K. O. Chang, N. C. Pedersen, Reversal of the progression of fatal coronavirus infection in cats by a broad-spectrum coronavirus protease inhibitor. PLOS Pathog. 12, 1\u201318 (2016).","journal-title":"PLOS Pathog."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/1098612X17729626"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl4784"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2118542"},{"key":"e_1_3_2_13_2","unstructured":"FDA (US) \u201cEmergency Use Authorization for Paxlovid (nirmatrelvir tablets co-packaged with ritonavir tablets)\u201d (2021)."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00117"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac933"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000033024"},{"key":"e_1_3_2_17_2","unstructured":"PDMA (Japan) \u201cXocova Tablets 125 mg Shionogi & Co. Ltd. review report\u201d (2022)."},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","unstructured":"X. Chen X. Huang Q. Ma P. Kuzmi\u010d B. Zhou J. Xu B. Liu H. Jiang W. Zhang C. Yang S. Wu J. Huang H. Li C. Long X. Zhao H. Xu Y. Sheng Y. Guo C. Niu L. Xue Y. Xu J. Liu T. Zhang J. Spencer W. Deng S.-H. Chen Z. Yang N. Zhong Inhibition mechanism and antiviral activity of an \u03b1-ketoamide based SARS-CoV-2 main protease inhibitor. bioRxiv 531862 [Preprint]. 2023. https:\/\/doi.org\/10.1101\/2023.03.09.531862.","DOI":"10.21203\/rs.3.rs-2634509\/v1"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.102189"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42102-y"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2301425"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1039\/D3MD00493G"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00840-23"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2023.12.004"},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","unstructured":"M. Sedova L. Jaroszewski M. Iyer A. Godzik Monitoring for SARS-CoV-2 drug resistance mutations in broad viral populations. bioRxiv 493798 [Preprint]. 2022. https:\/\/doi.org\/10.1101\/2022.05.27.493798.","DOI":"10.1101\/2022.05.27.493798"},{"key":"e_1_3_2_26_2","first-page":"acscentsci.3c00","article-title":"Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir","author":"Hu Y.","year":"2023","unstructured":"Y. Hu, E. M. Lewandowski, H. Tan, X. Zhang, R. T. Morgan, X. Zhang, L. M. C. Jacobs, S. G. Butler, M. V. Gongora, J. Choy, X. Deng, Y. Chen, J. Wang, Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir. ACS Cent. Sci., acscentsci.3c00538 (2023).","journal-title":"ACS Cent. Sci."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.103004"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.3c00054"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00869-22"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104559"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/vead055"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.77433"},{"key":"e_1_3_2_33_2","unstructured":"FDA (US) \u201cFact Sheet for Healthcare Providers: Emergency Use Authorization for Paxlovid (Revised 02\/2023)\u201d (2023)."},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05514-2"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add7197"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02815-22"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade8778"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.2c00489"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37773-6"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39704-x"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40018-1"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abq7360"},{"key":"e_1_3_2_43_2","doi-asserted-by":"crossref","unstructured":"F. Costacurta A. Dodaro D. Bante H. Sch\u00f6ppe B. Sprenger S. A. Moghadasi J. Fleischmann M. Pavan D. Bassani S. Menin S. Rauch L. Krismer A. Sauerwein A. Heberle T. Rabensteiner J. Ho R. S. Harris E. Stefan R. Schneider T. Kaserer S. Moro D. Von Laer E. Heilmann A comprehensive study of SARS-CoV-2 main protease (Mpro) inhibitor-resistant mutants selected in a VSV-based system. bioRxiv 558628 [Preprint]. 2023. https:\/\/doi.org\/10.1101\/2023.09.22.558628.","DOI":"10.1101\/2023.09.22.558628"},{"key":"e_1_3_2_44_2","doi-asserted-by":"crossref","unstructured":"S. Lan G. Neilsen R. L. Slack W. A. Cantara A. E. Castaner Z. C. Lorson N. Lulkin H. Zhang J. Lee M. E. Cilento P. R. Tedbury S. G. Sarafianos Nirmatrelvir resistance in SARS-CoV-2 Omicron_BA.1 and WA1 replicons and escape strategies. bioRxiv 22389 [Preprint]. 2023. https:\/\/doi.org\/10.1101\/2022.12.31.522389.","DOI":"10.1101\/2022.12.31.522389"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.3c00125"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06609-0"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44259-023-00009-0"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.3c01269"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad494"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2023.08.001"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2016.03.010"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009482"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1010494"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1649889"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2004.01.022"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0896(95)00105-P"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01828"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb3405"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm0603926"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf1611"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb4489"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01177"},{"key":"e_1_3_2_63_2","doi-asserted-by":"crossref","unstructured":"A. Vasudevan M. A. Argiriadi A. Baranczak M. M. Friedman J. Gavrilyuk A. D. Hobson J. J. Hulce S. Osman N. S. Wilson Covalent Binders in Drug Discovery vol. 58 of Progress in Medicinal Chemistry (Elsevier B.V. 2019). http:\/\/dx.doi.org\/10.1016\/bs.pmch.2018.12.002.","DOI":"10.1016\/bs.pmch.2018.12.002"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2223-y"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502577200"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18233-x"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0356-z"},{"key":"e_1_3_2_68_2","article-title":"Broad-spectrum inhibition of coronavirus main and papain-like proteases by HCV drugs","author":"Anson B.","year":"2020","unstructured":"B. Anson, M. Chapman, E. Lendy, S. Pshenychnyi, R. D\u2019Aquila, K. Satchell, A. Mesecar, Broad-spectrum inhibition of coronavirus main and papain-like proteases by HCV drugs. Res. Sq. (2020), doi: 10.21203\/rs.3.rs-26344\/v1.","journal-title":"Res. Sq."},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027228"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01123-12"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.20.11000"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm9805384"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.6.2267-2275.2005"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-020-00689-z"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b00686"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01808"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(00)00122-X"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00049-15"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.0c00110"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1MD00247C"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1177\/10915818221095489"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2013.02.010"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.0c00815"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00677-09"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2018.07.020"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31210-w"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0616302"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26239-2"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00404"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2009.12.4272"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102023"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abo7201"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00758-22"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28354-0"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-022-01119-7"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01392-w"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40556-8"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.5b00647"},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.3390\/v11020197"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.14.50"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867043364270"},{"key":"e_1_3_2_102_2","doi-asserted-by":"crossref","unstructured":"P. Weerawarna Main proteases of Key RNA Viruses Including Coronavirus Recognize P2 Residues in the Polyproline Type II Conformation: Harnessing Proline\u2019s Unique Conformation for Protease Inhibitors. ChemRxiv (2023). http:\/\/dx.doi.org\/10.26434\/chemrxiv-2023-lfxqv-v2.","DOI":"10.26434\/chemrxiv-2023-lfxqv-v2"},{"key":"e_1_3_2_103_2","doi-asserted-by":"publisher","DOI":"10.1039\/D0MD00370K"},{"key":"e_1_3_2_104_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2015.18"},{"key":"e_1_3_2_105_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad102"},{"key":"e_1_3_2_106_2","doi-asserted-by":"publisher","DOI":"10.7326\/M23-1756"},{"key":"e_1_3_2_107_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2005.02.004"},{"key":"e_1_3_2_108_2","doi-asserted-by":"publisher","DOI":"10.1002\/bmb.20479"},{"key":"e_1_3_2_109_2","doi-asserted-by":"crossref","unstructured":"R. A. Copeland Evaluation of Enzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists and Pharmacologists (Wiley ed. 2 2013). https:\/\/onlinelibrary.wiley.com\/doi\/book\/10.1002\/9781118540398).","DOI":"10.1002\/9781118540398"},{"key":"e_1_3_2_110_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(73)90196-2"},{"key":"e_1_3_2_111_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2008.12.024"},{"key":"e_1_3_2_112_2","doi-asserted-by":"publisher","DOI":"10.1107\/S1600576716000649"},{"key":"e_1_3_2_113_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909047337"},{"key":"e_1_3_2_114_2","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798317017235"},{"key":"e_1_3_2_115_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444905036693"},{"key":"e_1_3_2_116_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444913000061"},{"key":"e_1_3_2_117_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444994003112"},{"key":"e_1_3_2_118_2","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798317016035"},{"key":"e_1_3_2_119_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889807021206"},{"key":"e_1_3_2_120_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444996012255"},{"key":"e_1_3_2_121_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904019158"},{"key":"e_1_3_2_122_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19619-7"},{"key":"e_1_3_2_123_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.12.004"},{"key":"e_1_3_2_124_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2708-8"},{"key":"e_1_3_2_125_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2111593118"},{"key":"e_1_3_2_126_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2020.05.015"},{"key":"e_1_3_2_127_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.23013"},{"key":"e_1_3_2_128_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2017.09.005"},{"key":"e_1_3_2_129_2","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.12820"},{"key":"e_1_3_2_130_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2010.01.007"},{"key":"e_1_3_2_131_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328332c3a5"},{"key":"e_1_3_2_132_2","doi-asserted-by":"publisher","DOI":"10.4103\/0976-0105.177703"},{"key":"e_1_3_2_133_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.050"},{"key":"e_1_3_2_134_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01702-06"},{"key":"e_1_3_2_135_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035421"},{"key":"e_1_3_2_136_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2020.10.007"},{"key":"e_1_3_2_137_2","first-page":"2020","article-title":"Structural basis for the inhibition of the SARS-CoV-2 main protease by the anti-HCV drug narlaprevir","volume":"6","author":"Bai Y.","year":"2021","unstructured":"Y. Bai, F. Ye, Y. Feng, H. Liao, H. Song, J. Qi, G. F. Gao, W. Tan, L. Fu, Y. Shi, Structural basis for the inhibition of the SARS-CoV-2 main protease by the anti-HCV drug narlaprevir. Signal Transduct. Target. Ther. 6, 2020\u20132022 (2021).","journal-title":"Signal Transduct. Target. Ther."},{"key":"e_1_3_2_138_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-15930-z"},{"key":"e_1_3_2_139_2","doi-asserted-by":"publisher","DOI":"10.1107\/S2052252521001159"},{"key":"e_1_3_2_140_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41557-021-00707-0"},{"key":"e_1_3_2_141_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2603"},{"key":"e_1_3_2_142_2","doi-asserted-by":"publisher","DOI":"10.3390\/v13091735"},{"key":"e_1_3_2_143_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-021-00883-2"},{"key":"e_1_3_2_144_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00095a005"},{"key":"e_1_3_2_145_2","unstructured":"O. Dafydd Rhys M. Y. Pettersson M. R. Reese M. F. Sammons J. B. Tuttle P. R. Verhoes L. Wei Q. Yang X. Yang WO 2021\/250648 A1 (2021)."},{"key":"e_1_3_2_146_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2015.08.010"},{"key":"e_1_3_2_147_2","first-page":"22","article-title":"The discovery and development of boceprevir: A novel, first-generation inhibitor of the hepatitis C virus NS3\/4A serine protease","volume":"1","author":"Howe A. Y. M.","year":"2013","unstructured":"A. Y. M. Howe, S. Venkatraman, The discovery and development of boceprevir: A novel, first-generation inhibitor of the hepatitis C virus NS3\/4A serine protease. J. Clin. Transl. Hepatol. 1, 22\u201332 (2013).","journal-title":"J. Clin. Transl. Hepatol."},{"key":"e_1_3_2_148_2","unstructured":"FDA (US) \u201cApplication 202258Orig1s000\u201d (2009)."}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adi0979","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T13:59:23Z","timestamp":1710338363000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adi0979"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,13]]},"references-count":147,"journal-issue":{"issue":"738","published-print":{"date-parts":[[2024,3,13]]}},"alternative-id":["10.1126\/scitranslmed.adi0979"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adi0979","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.09.15.275891","asserted-by":"object"}]},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,13]]},"assertion":[{"value":"2023-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadi0979"}}