Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections

{ 'indexed': {'date-parts': [[2024, 9, 20]], 'date-time': '2024-09-20T04:31:31Z', 'timestamp': 1726806691582}, 'reference-count': 57, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2024, 9, 18]], 'date-time': '2024-09-18T00:00:00Z', 'timestamp': 1726617600000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2024, 9, 18]], 'date-time': '2024-09-18T00:00:00Z', 'timestamp': 1726617600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': '<jats:title>Abstract</jats:title><jats:p>We investigated the impact of antiviral treatment on ' 'the emergence of SARS-CoV-2 resistance during persistent infections in immunocompromised ' 'patients (<jats:italic>n</jats:italic>\u2009=\u200915). All patients received remdesivir and ' 'some also received nirmatrelvir-ritonavir (<jats:italic>n</jats:italic>\u2009=\u20093) or ' 'therapeutic monoclonal antibodies (<jats:italic>n</jats:italic>\u2009=\u20094). Sequence ' 'analysis showed that nine patients carried viruses with mutations in the nsp12 (RNA dependent ' 'RNA polymerase), while four had viruses with nsp5 (3C protease) mutations. Infectious ' 'SARS-CoV-2 with a double mutation in nsp5 (T169I) and nsp12 (V792I) was recovered from ' 'respiratory secretions 77 days after initial COVID-19 diagnosis from a patient ' 'sequentially\xa0treated with nirmatrelvir-ritonavir\xa0and remdesivir. In vitro ' 'characterization confirmed its decreased sensitivity to remdesivir and nirmatrelvir, which ' 'was overcome by combined antiviral treatment. Studies in golden Syrian hamsters demonstrated ' 'efficient transmission to contact animals. This study documents the isolation of SARS-CoV-2 ' 'carrying resistance mutations to both nirmatrelvir and remdesivir from a patient and ' 'demonstrates its transmissibility in vivo.</jats:p>', 'DOI': '10.1038/s41467-024-51924-3', 'type': 'journal-article', 'created': {'date-parts': [[2024, 9, 19]], 'date-time': '2024-09-19T21:05:46Z', 'timestamp': 1726779946000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in ' 'immunocompromised patients with persistent infections', 'prefix': '10.1038', 'volume': '15', 'author': [ {'given': 'Mohammed', 'family': 'Nooruzzaman', 'sequence': 'first', 'affiliation': []}, {'given': 'Katherine E. 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COVID-19 severity and survival over time in ' 'patients with hematologic malignancies: a Population-Based Registry ' 'Study. Cancers 15, 1497 (2023).', 'journal-title': 'Cancers'}, { 'key': '51924_CR2', 'doi-asserted-by': 'publisher', 'first-page': 'e0011024', 'DOI': '10.1128/mbio.00110-24', 'volume': '15', 'author': 'AD Marques', 'year': '2024', 'unstructured': 'Marques, A. D. et al. SARS-CoV-2 evolution during prolonged infection in ' 'immunocompromised patients. mBio 15, e0011024 (2024).', 'journal-title': 'mBio'}, { 'key': '51924_CR3', 'doi-asserted-by': 'publisher', 'first-page': 'e2473', 'DOI': '10.1002/rmv.2473', 'volume': '33', 'author': 'H Tian', 'year': '2023', 'unstructured': 'Tian, H. et al. Efficacy and safety of paxlovid (nirmatrelvir/ritonavir) ' 'in the treatment of COVID‐19: an updated meta‐analysis and trial ' 'sequential analysis. Rev. Med. Virol. 33, e2473 (2023).', 'journal-title': 'Rev. Med. Virol.'}, { 'key': '51924_CR4', 'doi-asserted-by': 'publisher', 'first-page': '305', 'DOI': '10.1056/NEJMoa2116846', 'volume': '386', 'author': 'RL Gottlieb', 'year': '2022', 'unstructured': 'Gottlieb, R. L. et al. Early remdesivir to prevent progression to severe ' 'covid-19 in outpatients. New Engl. J. Med. 386, 305–315 (2022).', 'journal-title': 'New Engl. J. Med.'}, { 'key': '51924_CR5', '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. New Engl. J. Med. 383, 1813–1826 (2020).', 'journal-title': 'New Engl. J. Med.'}, { 'key': '51924_CR6', '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. J. Am. Med. Assoc. ' '324, 1048 (2020).', 'journal-title': 'J. Am. Med. Assoc.'}, { 'key': '51924_CR7', 'doi-asserted-by': 'publisher', 'first-page': '1667', 'DOI': '10.1093/infdis/jiad324', 'volume': '228', 'author': 'D Paraskevis', 'year': '2023', 'unstructured': 'Paraskevis, D. et al. Real-world effectiveness of molnupiravir and ' 'nirmatrelvir/ritonavir as treatments for COVID-19 in patients at high ' 'risk. J. Infect. Dis. 228, 1667–1674 (2023).', 'journal-title': 'J. Infect. Dis.'}, { 'key': '51924_CR8', 'doi-asserted-by': 'publisher', 'first-page': '453', 'DOI': '10.1093/cid/ciac781', 'volume': '76', 'author': 'R Najjar-Debbiny', 'year': '2023', 'unstructured': 'Najjar-Debbiny, R. et al. Effectiveness of molnupiravir in high-risk ' 'patients: a propensity score matched analysis. Clin. Infect. Dis. 76, ' '453–460 (2023).', 'journal-title': 'Clin. Infect. Dis.'}, { 'key': '51924_CR9', 'doi-asserted-by': 'publisher', 'first-page': '594', 'DOI': '10.1038/s41586-023-06649-6', 'volume': '623', 'author': 'T Sanderson', 'year': '2023', 'unstructured': 'Sanderson, T. et al. A molnupiravir-associated mutational signature in ' 'global SARS-CoV-2 genomes. Nature 623, 594–600 (2023).', 'journal-title': 'Nature'}, { 'key': '51924_CR10', 'doi-asserted-by': 'publisher', 'first-page': '100735', 'DOI': '10.1016/j.xcrm.2022.100735', 'volume': '3', 'author': 'A Heyer', 'year': '2022', 'unstructured': 'Heyer, A. et al. Remdesivir-induced emergence of SARS-CoV2 variants in ' 'patients with prolonged infection. Cell Rep. Med. 3, 100735 (2022).', 'journal-title': 'Cell Rep. Med.'}, { 'key': '51924_CR11', 'doi-asserted-by': 'publisher', 'first-page': '486', 'DOI': '10.1038/d41586-023-03248-3', 'volume': '623', 'author': 'SL Kosakovsky Pond', 'year': '2023', 'unstructured': 'Kosakovsky Pond, S. L. & Martin, D. Anti-COVID drug accelerates viral ' 'evolution. Nature 623, 486–487 (2023).', 'journal-title': 'Nature'}, { 'key': '51924_CR12', 'doi-asserted-by': 'publisher', 'first-page': '376', 'DOI': '10.1038/s41586-023-06609-0', 'volume': '622', 'author': 'Y Duan', 'year': '2023', 'unstructured': 'Duan, Y. et al. Molecular mechanisms of SARS-CoV-2 resistance to ' 'nirmatrelvir. Nature 622, 376–382 (2023).', 'journal-title': 'Nature'}, { 'key': '51924_CR13', 'doi-asserted-by': 'publisher', 'first-page': '558', 'DOI': '10.1038/s41586-022-05514-2', 'volume': '613', 'author': 'S Iketani', 'year': '2023', 'unstructured': 'Iketani, S. et al. Multiple pathways for SARS-CoV-2 resistance to ' 'nirmatrelvir. Nature 613, 558–564 (2023).', 'journal-title': 'Nature'}, { 'key': '51924_CR14', 'doi-asserted-by': 'publisher', 'first-page': '2096', 'DOI': '10.3390/microorganisms11082096', 'volume': '11', 'author': 'S Yang', 'year': '2023', 'unstructured': 'Yang, S. et al. Transient SARS-CoV-2 RNA-dependent RNA polymerase ' 'mutations after remdesivir treatment for chronic COVID-19 in two ' 'transplant recipients: case report and intra-host viral genomic ' 'investigation. Microorganisms 11, 2096 (2023).', 'journal-title': 'Microorganisms'}, { 'key': '51924_CR15', 'doi-asserted-by': 'publisher', 'first-page': 'eabo0718', 'DOI': '10.1126/scitranslmed.abo0718', 'volume': '14', 'author': 'LJ Stevens', 'year': '2022', 'unstructured': 'Stevens, L. J. et al. Mutations in the SARS-CoV-2 RNA-dependent RNA ' 'polymerase confer resistance to remdesivir by distinct mechanisms. Sci. ' 'Transl. Med. 14, eabo0718 (2022).', 'journal-title': 'Sci. Transl. Med'}, { 'key': '51924_CR16', 'unstructured': 'https://www.gilead.com/-/media/files/pdfs/medicines/covid-19/veklury/veklury_pi.pdf ' '(2024).'}, { 'key': '51924_CR17', 'doi-asserted-by': 'publisher', 'first-page': 'e235', 'DOI': '10.1016/S2666-5247(23)00336-1', 'volume': '5', 'author': 'Z Raglow', 'year': '2024', 'unstructured': 'Raglow, Z. et al. SARS-CoV-2 shedding and evolution in patients who were ' 'immunocompromised during the omicron period: a multicentre, prospective ' 'analysis. Lancet Microbe 5, e235–e246 (2024).', 'journal-title': 'Lancet Microbe'}, { 'key': '51924_CR18', 'doi-asserted-by': 'publisher', 'first-page': '277', 'DOI': '10.1038/s41586-021-03291-y', 'volume': '592', 'author': 'SA Kemp', 'year': '2021', 'unstructured': 'Kemp, S. A. et al. SARS-CoV-2 evolution during treatment of chronic ' 'infection. Nature 592, 277–282 (2021).', 'journal-title': 'Nature'}, { 'key': '51924_CR19', 'doi-asserted-by': 'publisher', 'first-page': '138', 'DOI': '10.1038/s41392-022-00992-2', 'volume': '7', 'author': 'J Ou', 'year': '2022', 'unstructured': 'Ou, J. et al. Tracking SARS-CoV-2 Omicron diverse spike gene mutations ' 'identifies multiple inter-variant recombination events. Signal ' 'Transduct. Target Ther. 7, 138 (2022).', 'journal-title': 'Signal Transduct. Target Ther.'}, { 'key': '51924_CR20', 'doi-asserted-by': 'crossref', 'unstructured': 'Huygens, S., Oude Munnink, B., Gharbharan, A., Koopmans, M. & Rijnders, ' 'B. Sotrovimab resistance and viral persistence after treatment of ' 'immunocompromised patients infected with the severe acute respiratory ' 'syndrome coronavirus 2 Omicron variant. Clin. Infect. Dis. 76, e507–e509 ' '(2023).', 'DOI': '10.1093/cid/ciac601'}, { 'key': '51924_CR21', 'doi-asserted-by': 'publisher', 'first-page': '240', 'DOI': '10.1016/j.cmi.2022.08.021', 'volume': '29', 'author': 'C Andrés', 'year': '2023', 'unstructured': 'Andrés, C. et al. Emergence of Delta and Omicron variants carrying ' 'resistance-associated mutations in immunocompromised patients undergoing ' 'sotrovimab treatment with long-term viral excretion. Clin. Microbiol. ' 'Infect. 29, 240–246 (2023).', 'journal-title': 'Clin. Microbiol. Infect.'}, { 'key': '51924_CR22', 'doi-asserted-by': 'publisher', 'first-page': '1104', 'DOI': '10.1001/jama.2022.13854', 'volume': '328', 'author': 'E Birnie', 'year': '2022', 'unstructured': 'Birnie, E. et al. Development of resistance-associated mutations after ' 'sotrovimab administration in high-risk individuals infected with the ' 'SARS-CoV-2 Omicron variant. J. Am. Med. Assoc. 328, 1104 (2022).', 'journal-title': 'J. Am. Med. Assoc.'}, { 'key': '51924_CR23', 'doi-asserted-by': 'publisher', 'first-page': '1477', 'DOI': '10.1056/NEJMc2120219', 'volume': '386', 'author': 'R Rockett', 'year': '2022', 'unstructured': 'Rockett, R. et al. Resistance mutations in SARS-CoV-2 delta variant ' 'after sotrovimab use. New Engl. J. Med. 386, 1477–1479 (2022).', 'journal-title': 'New Engl. J. Med.'}, { 'key': '51924_CR24', 'doi-asserted-by': 'publisher', 'first-page': '1263', 'DOI': '10.1093/infdis/jiad270', 'volume': '228', 'author': 'C Hedskog', 'year': '2023', 'unstructured': 'Hedskog, C. et al. Viral resistance analyses from the remdesivir phase 3 ' 'adaptive COVID-19 treatment trial-1 (ACTT-1). J. Infect. Dis. 228, ' '1263–1273 (2023).', 'journal-title': 'J. Infect. Dis.'}, { 'key': '51924_CR25', 'doi-asserted-by': 'publisher', 'first-page': 'veac050', 'DOI': '10.1093/ve/veac050', 'volume': '8', 'author': 'SAJ Wilkinson', 'year': '2022', 'unstructured': 'Wilkinson, S. A. J. et al. Recurrent SARS-CoV-2 mutations in ' 'immunodeficient patients. Virus Evol. 8, veac050 (2022).', 'journal-title': 'Virus Evol.'}, { 'key': '51924_CR26', 'doi-asserted-by': 'publisher', 'first-page': '1658', 'DOI': '10.1021/acscentsci.3c00538', 'volume': '9', 'author': 'Y Hu', 'year': '2023', 'unstructured': 'Hu, Y. et al. Naturally occurring mutations of SARS-CoV-2 main protease ' 'confer drug resistance to nirmatrelvir. ACS Cent. Sci. 9, 1658–1669 ' '(2023).', 'journal-title': 'ACS Cent. Sci.'}, { 'key': '51924_CR27', 'doi-asserted-by': 'publisher', 'first-page': '104559', 'DOI': '10.1016/j.ebiom.2023.104559', 'volume': '91', 'author': 'JD Ip', 'year': '2023', 'unstructured': 'Ip, J. D. et al. Global prevalence of SARS-CoV-2 3CL protease mutations ' 'associated with nirmatrelvir or ensitrelvir resistance. EBioMedicine 91, ' '104559 (2023).', 'journal-title': 'EBioMedicine'}, { 'key': '51924_CR28', 'doi-asserted-by': 'publisher', 'first-page': 'eadd7197', 'DOI': '10.1126/sciadv.add7197', 'volume': '8', 'author': 'Y Zhou', 'year': '2022', 'unstructured': 'Zhou, Y. et al. Nirmatrelvir-resistant SARS-CoV-2 variants with high ' 'fitness in an infectious cell culture system. Sci. Adv. 8, eadd7197 ' '(2022).', 'journal-title': 'Sci. Adv.'}, { 'key': '51924_CR29', 'doi-asserted-by': 'publisher', 'first-page': '352', 'DOI': '10.1093/cid/ciad494', 'volume': '78', 'author': 'NS Zuckerman', 'year': '2024', 'unstructured': 'Zuckerman, N. S., Bucris, E., Keidar-Friedman, D., Amsalem, M. & ' 'Brosh-Nissimov, T. Nirmatrelvir resistance—de novo E166V/L50V mutations ' 'in an immunocompromised patient treated with prolonged ' 'nirmatrelvir/ritonavir monotherapy leading to clinical and virological ' 'treatment failure—a case report. Clin. Infect. Dis. 78, 352–355 (2024).', 'journal-title': 'Clin. Infect. Dis.'}, { 'key': '51924_CR30', 'doi-asserted-by': 'publisher', 'first-page': 'eade8778', 'DOI': '10.1126/sciadv.ade8778', 'volume': '9', 'author': 'SA Moghadasi', 'year': '2023', 'unstructured': 'Moghadasi, S. A. et al. Transmissible SARS-CoV-2 variants with ' 'resistance to clinical protease inhibitors. Sci. Adv. 9, eade8778 ' '(2023).', 'journal-title': 'Sci. Adv.'}, { 'key': '51924_CR31', 'doi-asserted-by': 'publisher', 'first-page': '877', 'DOI': '10.1007/s15010-023-02125-5', 'volume': '52', 'author': 'HM Orth', 'year': '2024', 'unstructured': 'Orth, H. M. et al. Early combination therapy of COVID-19 in high-risk ' 'patients. Infection 52, 877–889 (2024).', 'journal-title': 'Infection'}, { 'key': '51924_CR32', 'doi-asserted-by': 'publisher', 'first-page': '280', 'DOI': '10.1093/cid/ciad181', 'volume': '77', 'author': 'M Mikulska', 'year': '2023', 'unstructured': 'Mikulska, M. et al. Triple combination therapy with 2 antivirals and ' 'monoclonal antibodies for persistent or relapsed severe acute ' 'respiratory syndrome coronavirus 2 infection in immunocompromised ' 'patients. Clin. Infect. Dis. 77, 280–286 (2023).', 'journal-title': 'Clin. Infect. Dis.'}, { 'key': '51924_CR33', 'doi-asserted-by': 'publisher', 'first-page': '813', 'DOI': '10.1016/j.medj.2023.08.001', 'volume': '4', 'author': 'Y Hirotsu', 'year': '2023', 'unstructured': 'Hirotsu, Y. et al. Multidrug-resistant mutations to antiviral and ' 'antibody therapy in an immunocompromised patient infected with ' 'SARS-CoV-2. Med. 4, 813–824.e4 (2023).', 'journal-title': 'Med'}, { 'key': '51924_CR34', 'doi-asserted-by': 'publisher', 'first-page': '809937', 'DOI': '10.3389/fimmu.2021.809937', 'volume': '12', 'author': 'AF Rendeiro', 'year': '2022', 'unstructured': 'Rendeiro, A. F. et al. Metabolic and immune markers for precise ' 'monitoring of COVID-19 severity and treatment. Front. Immunol. 12, ' '809937 (2022).', 'journal-title': 'Front. Immunol.'}, { 'key': '51924_CR35', 'doi-asserted-by': 'publisher', 'first-page': 'e202000955', 'DOI': '10.26508/lsa.202000955', 'volume': '4', 'author': 'AF Rendeiro', 'year': '2021', 'unstructured': 'Rendeiro, A. F. et al. Profiling of immune dysfunction in COVID-19 ' 'patients allows early prediction of disease progression. Life Sci. ' 'Alliance 4, e202000955 (2021).', 'journal-title': 'Life Sci. Alliance'}, { 'key': '51924_CR36', 'doi-asserted-by': 'publisher', 'first-page': '1879', 'DOI': '10.1038/s41590-023-01637-4', 'volume': '24', 'author': 'T Kusakabe', 'year': '2023', 'unstructured': 'Kusakabe, T. et al. Fungal microbiota sustains lasting immune activation ' 'of neutrophils and their progenitors in severe COVID-19. Nat. Immunol. ' '24, 1879–1889 (2023).', 'journal-title': 'Nat. Immunol.'}, { 'key': '51924_CR37', 'doi-asserted-by': 'publisher', 'first-page': '104428', 'DOI': '10.1016/j.jcv.2020.104428', 'volume': '128', 'author': 'MC Smithgall', 'year': '2020', 'unstructured': 'Smithgall, M. C., Scherberkova, I., Whittier, S. & Green, D. A. ' 'Comparison of cepheid Xpert Xpress and Abbott ID now to Roche Cobas for ' 'the rapid detection of SARS-CoV-2. J. Clin. Virol. 128, 104428 (2020).', 'journal-title': 'J. Clin. Virol.'}, { 'key': '51924_CR38', 'doi-asserted-by': 'publisher', 'first-page': '297', 'DOI': '10.1126/science.abc1917', 'volume': '369', 'author': 'AS Gonzalez-Reiche', 'year': '2020', 'unstructured': 'Gonzalez-Reiche, A. S. et al. Introductions and early spread of ' 'SARS-CoV-2 in the New York City area. Science 369, 297–301 (2020).', 'journal-title': 'Science'}, { 'key': '51924_CR39', 'doi-asserted-by': 'publisher', 'first-page': 'e0104623', 'DOI': '10.1128/mbio.01046-23', 'volume': '14', 'author': 'AE Roder', 'year': '2023', 'unstructured': 'Roder, A. E. et al. Optimized quantification of intra-host viral ' 'diversity in SARS-CoV-2 and influenza virus sequence data. mBio 14, ' 'e0104623 (2023).', 'journal-title': 'mBio'}, { 'key': '51924_CR40', 'doi-asserted-by': 'publisher', 'first-page': '2078', 'DOI': '10.1093/bioinformatics/btp352', 'volume': '25', 'author': 'H Li', 'year': '2009', 'unstructured': 'Li, H. et al. The Sequence Alignment/Map format and SAMtools. ' 'Bioinformatics 25, 2078–2079 (2009).', 'journal-title': 'Bioinformatics'}, { 'key': '51924_CR41', 'unstructured': 'Li, H. Aligning sequence reads, clone sequences and assembly contigs ' 'with BWA-MEM. Preprint at https://arxiv.org/abs/1303.3997 (2013).'}, { 'key': '51924_CR42', 'doi-asserted-by': 'publisher', 'first-page': '2114', 'DOI': '10.1093/bioinformatics/btu170', 'volume': '30', 'author': 'AM Bolger', 'year': '2014', 'unstructured': 'Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer ' 'for Illumina sequence data. Bioinformatics 30, 2114–2120 (2014).', 'journal-title': 'Bioinformatics'}, { 'key': '51924_CR43', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s13059-018-1618-7', 'volume': '20', 'author': 'ND Grubaugh', 'year': '2019', 'unstructured': 'Grubaugh, N. D. et al. An amplicon-based sequencing framework for ' 'accurately measuring intrahost virus diversity using PrimalSeq and iVar. ' 'Genome Biol. 20, 8 (2019).', 'journal-title': 'Genome Biol.'}, { 'key': '51924_CR44', 'unstructured': 'Van der Auwera, G. A. & O’Connor, B. D. Genomics in The Cloud: Using ' 'Docker, GATK, and WDL in Terra (O’Reilly Media, 2020).'}, { 'key': '51924_CR45', 'doi-asserted-by': 'publisher', 'first-page': '3773', 'DOI': '10.21105/joss.03773', 'volume': '6', 'author': 'I Aksamentov', 'year': '2021', 'unstructured': 'Aksamentov, I., Roemer, C., Hodcroft, E. & Neher, R. Nextclade: clade ' 'assignment, mutation calling and quality control for viral genomes. J. ' 'Open Source Softw. 6, 3773 (2021).', 'journal-title': 'J. Open Source Softw.'}, { 'key': '51924_CR46', 'doi-asserted-by': 'publisher', 'first-page': '1735', 'DOI': '10.1093/bioinformatics/btab856', 'volume': '38', 'author': 'C Chen', 'year': '2022', 'unstructured': 'Chen, C. et al. CoV-Spectrum: analysis of globally shared SARS-CoV-2 ' 'data to identify and characterize new variants. Bioinformatics 38, ' '1735–1737 (2022).', 'journal-title': 'Bioinformatics'}, { 'key': '51924_CR47', 'doi-asserted-by': 'publisher', 'first-page': 'e0096122', 'DOI': '10.1128/jvi.00961-22', 'volume': '96', 'author': 'M Martins', 'year': '2022', 'unstructured': 'Martins, M. et al. The Omicron variant BA.1.1 presents a lower ' 'pathogenicity than B.1 D614G and Delta variants in a feline model of ' 'SARS-CoV-2 infection. J. Virol. 96, e0096122 (2022).', 'journal-title': 'J. Virol.'}, { 'key': '51924_CR48', 'doi-asserted-by': 'publisher', 'first-page': '104886', 'DOI': '10.1016/j.jbc.2023.104886', 'volume': '299', 'author': 'A Kovalevsky', 'year': '2023', 'unstructured': 'Kovalevsky, A. et al. Contribution of the catalytic dyad of SARS-CoV-2 ' 'main protease to binding covalent and noncovalent inhibitors. J. Biol. ' 'Chem. 299, 104886 (2023).', 'journal-title': 'J. Biol. Chem.'}, { 'key': '51924_CR49', 'doi-asserted-by': 'publisher', 'first-page': '1499', 'DOI': '10.1126/science.abc1560', 'volume': '368', 'author': 'W Yin', 'year': '2020', 'unstructured': 'Yin, W. et al. Structural basis for inhibition of the RNA-dependent RNA ' 'polymerase from SARS-CoV-2 by remdesivir. Science 368, 1499–1504 (2020).', 'journal-title': 'Science'}, { 'key': '51924_CR50', 'doi-asserted-by': 'publisher', 'first-page': 'W296', 'DOI': '10.1093/nar/gky427', 'volume': '46', 'author': 'A Waterhouse', 'year': '2018', 'unstructured': 'Waterhouse, A. et al. SWISS-MODEL: homology modelling of protein ' 'structures and complexes. Nucleic Acids Res. 46, W296–W303 (2018).', 'journal-title': 'Nucleic Acids Res.'}, { 'key': '51924_CR51', 'doi-asserted-by': 'publisher', 'first-page': '283', 'DOI': '10.1107/S0021889892009944', 'volume': '26', 'author': 'RA Laskowski', 'year': '1993', 'unstructured': 'Laskowski, R. A., MacArthur, M. W., Moss, D. S. & Thornton, J. M. ' 'PROCHECK: a program to check the stereochemical quality of protein ' 'structures. J. Appl Crystallogr 26, 283–291 (1993).', 'journal-title': 'J. Appl Crystallogr'}, { 'key': '51924_CR52', 'unstructured': 'Schrödinger, L., & DeLano, W. PyMOL. Retrieved from ' 'http://www.pymol.org/pymol (2020).'}, { 'key': '51924_CR53', 'doi-asserted-by': 'crossref', 'unstructured': 'Steffen, C. et al. AutoDock4 and AutoDockTools4: automated docking with ' 'selective receptor flexibility. J. Comput. Chem. 31, 2785–2791 (2010).', 'DOI': '10.1002/jcc.21256'}, { 'key': '51924_CR54', 'doi-asserted-by': 'publisher', 'unstructured': 'Trott, O. & Olson, A. J. AutoDock Vina: Improving the speed and accuracy ' 'of docking with a new scoring function, efficient optimization, and ' 'multithreading. J. Comput. Chem. https://doi.org/10.1002/jcc.21334 ' '(2009).', 'DOI': '10.1002/jcc.21334'}, { 'key': '51924_CR55', 'doi-asserted-by': 'publisher', 'first-page': 'D1373', 'DOI': '10.1093/nar/gkac956', 'volume': '51', 'author': 'S Kim', 'year': '2023', 'unstructured': 'Kim, S. et al. PubChem 2023 update. Nucleic Acids Res. 51, D1373–D1380 ' '(2023).', 'journal-title': 'Nucleic Acids Res.'}, { 'key': '51924_CR56', 'doi-asserted-by': 'publisher', 'first-page': '243', 'DOI': '10.1007/978-1-4939-2269-7_19', 'volume': '1263', 'author': 'S Dallakyan', 'year': '2015', 'unstructured': 'Dallakyan, S. & Olson, A. J. Small-molecule library screening by docking ' 'with PyRx. Methods Mol. Biol. 1263, 243–250 (2015).', 'journal-title': 'Methods Mol. Biol.'}, { 'key': '51924_CR57', 'doi-asserted-by': 'publisher', 'first-page': '127', 'DOI': '10.1093/protein/8.2.127', 'volume': '8', 'author': 'AC Wallace', 'year': '1995', 'unstructured': 'Wallace, A. C., Laskowski, R. A. & Thornton, J. M. Ligplot: a program to ' 'generate schematic diagrams of protein-ligand interactions. Protein Eng. ' 'Des. Selection 8, 127–134 (1995).', 'journal-title': 'Protein Eng. Des. 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