Resistance-associated mutations to the anti-SARS-CoV-2 agent nirmatrelvir: Selection not induction.
SARS-CoV-2
genomes
mutations
nirmatrelvir
quasispecies
resistance
selection
Journal
Journal of medical virology
ISSN: 1096-9071
Titre abrégé: J Med Virol
Pays: United States
ID NLM: 7705876
Informations de publication
Date de publication:
Feb 2024
Feb 2024
Historique:
revised:
21
01
2024
received:
20
11
2023
accepted:
27
01
2024
medline:
16
2
2024
pubmed:
16
2
2024
entrez:
16
2
2024
Statut:
ppublish
Résumé
Mutations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resistance to antiprotease nirmatrelvir were reported. We aimed to detect them in SARS-CoV-2 genomes and quasispecies retrieved in our institute before drug availability in January 2022 and to analyze the impact of mutations on protease (3CLpro) structure. We sought for 38 3CLpro nirmatrelvir resistance mutations in a set of 62 673 SARS-CoV-2 genomes obtained in our institute from respiratory samples collected between 2020 and 2023 and for these mutations in SARS-CoV-2 quasispecies for 90 samples collected in 2020, using Python. SARS-CoV-2 protease with major mutation E166V was generated with Swiss Pdb Viewer and Molegro Molecular Viewer. We detected 22 (58%) of the resistance-associated mutations in 417 (0.67%) of the genomes analyzed; 325 (78%) of these genomes had been obtained from samples collected in 2020-2021. APOBEC signatures were found for 12/22 mutations. We also detected among viral quasispecies from 90 samples some minority reads harboring any of 15 nirmatrelvir resistance mutations, including E166V. Also, we predicted that E166V has a very limited effect on 3CLpro structure but may prevent drug attachment. Thus, we evidenced that mutations associated with nirmatrelvir resistance pre-existed in SARS-CoV-2 before drug availability. These findings further warrant SARS-CoV-2 genomic surveillance and SARS-CoV-2 quasispecies characterization.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e29462Subventions
Organisme : Agence Nationale de la Recherche
Informations de copyright
© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.
Références
Service RF. Bad news for paxlovid? resistance May be coming. Science. 2022;377:138-139. doi:10.1126/science.add8037
Sedova M, Jaroszewski L, Iyer M, Godzik A. Monitoring for SARS-CoV-2 drug resistance mutations in broad viral populations. bioRxiv. 2022. doi:10.1101/2022.05.27.493798
Jochmans D, Liu C, Donckers K, et al. The substitutions L50F, E166A and L167F in SARS-CoV-2 3CLpro are selected by a protease inhibitor. In Vitro Confer Resist Nirmat. 2022;6(7):495116. doi:10.1101/2022.06.07.495116
Zhou Y, Gammeltoft KA, Ryberg LA, et al. Nirmatrelvir-resistant SARS-CoV-2 variants with high fitness in an infectious cell culture system. Sci Adv. 2022;8:eadd7197. doi:10.1126/sciadv.add7197
Duan Y, Zhou H, Liu X, et al. Molecular mechanisms of SARS-CoV-2 resistance to nirmatrelvir. Nature. 2023;622:376-382. doi:10.1038/s41586-023-06609-0
Ip JD, Wing-Ho Chu A, Chan WM, et al. Global prevalence of SARS-CoV-2 3CL protease mutations associated with nirmatrelvir or ensitrelvir resistance. EBioMedicine. 2023;91:104559. doi:10.1016/j.ebiom.2023.104559
Zuckerman NS, 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. 2023:ciad494. doi:10.1093/cid/ciad494
Iketani S, Mohri H, Culbertson B, et al. Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir. Nature. 2023;613:558-564. doi:10.1038/s41586-022-05514-2
Focosi D, McConnell S, Shoham S, Casadevall A, Maggi F, Antonelli G. Nirmatrelvir and COVID-19: development, pharmacokinetics, clinical efficacy, resistance, relapse, and pharmacoeconomics. Int J Antimicrob Agents. 2023;61:106708. doi:10.1016/j.ijantimicag.2022.106708
Lederberg J, Lederberg EM. Replica plating and indirect selection of bacterial mutants. J Bacteriol. 1952;63:399-406. doi:10.1128/jb.63.3.399-406.1952
de Jong MD, Schuurman R, Lange JM, Boucher CA. Replication of a pre-existing resistant HIV-1 subpopulation in vivo after introduction of a strong selective drug pressure. Antivir Ther. 1996;1:33-41.
Paredes R, Lalama CM, Ribaudo HJ, et al. Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. J Infect Dis. 2010;201:662-671. doi:10.1086/650543
Colson P, Chaudet H, Delerce J, et al. Role of SARS-CoV-2 mutations in the evolution of the COVID-19 pandemic. bioRxiv. 2023. doi:10.1101/2023.05.01.538506
Colson P, Gautret P, Delerce J, et al. The emergence, spread and vanishing of a French SARS-CoV-2 variant exemplifies the fate of RNA virus epidemics and obeys the Mistigri rule. J Med Virol. 2023;95(1):e28102. doi:10.1002/jmv.28102
Aksamentov I, Roemer C, Hodcroft E, Neher R. Nextclade: clade assignment, mutation calling and quality control for viral genomes. J Open Source Software. 2021;6:3773. doi:10.5281/zenodo.5607694
Bader W, Delerce J, Aherfi S, La Scola B, Colson P. Quasispecies analysis of SARS-CoV-2 of 15 different lineages during the first year of the pandemic prompts scratching under the surface of consensus genome sequences. Int J Mol Sci. 2022;23:15658. doi:10.3390/ijms232415658
Bittrich S, Bhikadiya C, Bi C, et al. RCSB protein data bank: efficient searching and simultaneous access to one million computed structure models alongside the PDB structures enabled by architectural advances. J Mol Biol. 2023;435:167994. doi:10.1016/j.jmb.2023.167994
Khoda KM, Liu Y, Storey C. Generalized Polak-Ribière algorithm. J Optimizat Theo Applicat. 1992;75(1992):345-354. doi:10.1007/BF00941472
Froimowitz M. HyperChem: a software package for computational chemistry and molecular modeling. Biotechniques. 1993;14:1010-1013.
Fantini J, Azzaz F, Chahinian H, Yahi N. Electrostatic surface potential as a key parameter in virus transmission and evolution: how to manage future virus pandemics in the post-COVID-19 era. Viruses. 2023;15:284. doi:10.3390/v15020284
Kaplan W. Swiss-PDB viewer (Deep View). Brief Bioinform. 2001;2:195-197. doi:10.1093/bib/2.2.195
Hirotsu Y, Kobayashi H, Kakizaki Y, et al. Multidrug-resistant mutations to antiviral and antibody therapy in an immunocompromised patient infected with SARS-CoV-2. Med. 2023;4(11):813-824. doi:10.1016/j.medj.2023.08.001
Stoler N, Nekrutenko A. Sequencing error profiles of illumina sequencing instruments. NAR genomics and bioinformatics. 2021;3(1):lqab019. doi:10.1093/nargab/lqab019
Fox EJ, Reid-Bayliss KS, Emond MJ, Loeb LA. Accuracy of next generation sequencing platforms. Next Generat Sequen Applicat. 2014;1:1000106. doi:10.4172/jngsa.1000106
Lu IN, Muller CP, He FQ. Applying next-generation sequencing to unravel the mutational landscape in viral quasispecies. Virus Res. 2020;283:197963. doi:10.1016/j.virusres.2020.197963
Sun F, Wang X, Tan S, et al. SARS-CoV-2 quasispecies provides an advantage mutation pool for the epidemic variants. Microbiol Spect. 2021;9:e0026121. doi:10.1128/Spectrum.00261-21
Mótyán JA, Mahdi M, Hoffka G, Tőzsér J. Potential resistance of SARS-CoV-2 main protease (Mpro) against protease inhibitors: lessons learned from HIV-1 protease. Int J Mol Sci. 2022;23:3507. doi:10.3390/ijms23073507
Perelson AS. Modelling viral and immune system dynamics. Nat Rev Immunol. 2002;2:28-36. doi:10.1038/nri700
Sender R, Bar-On YM, Gleizer S, et al. The total number and mass of SARS-CoV-2 virions. Proc Nat Acad Sci. 2021;118:e2024815118. doi:10.1073/pnas.2024815118
Choi B, Choudhary MC, Regan J, et al. Persistence and evolution of SARS-CoV-2 in an immunocompromised host. N Engl J Med. 2020;383(23):2291-2293. doi:10.1056/NEJMc2031364
Colson P, Devaux CA, Lagier JC, Gautret P, Raoult D. A possible role of remdesivir and plasma therapy in the selective sweep and emergence of new SARS-CoV-2 variants. J Clin Med. 2021;10(15):3276. doi:10.3390/jcm10153276
Shimazu H, Wada D, Maruyama S, et al. Clinical experience of treatment of immunocompromised individuals with persistent SARS-CoV-2 infection based on drug resistance mutations determined by genomic analysis: a descriptive study. BMC Infect Dis. 2023;23(1):780. doi:10.1186/s12879-023-08797-6
Andrés C, González-Sánchez A, Jiménez M, 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. 2023;29(2):240-246. doi:10.1016/j.cmi.2022.08.021
Hogan JI, Duerr R, Dimartino D, et al. Remdesivir resistance in transplant recipients with persistent coronavirus disease 2019. Clin Infect Dis. 2023;76(2):342-345. doi:10.1093/cid/ciac769
Matveeva M, Lefebvre M, Chahinian H, Yahi N, Fantini J. Host membranes as drivers of virus evolution. Viruses. 2023;15:1854. doi:10.3390/v15091854
Pecori R, Di Giorgio S, Paulo Lorenzo J, Nina Papavasiliou F. Functions and consequences of AID/APOBEC-mediated DNA and RNA deamination. Nat Rev Genet. 2022;23:505-518. doi:10.1038/s41576-022-00459-8
Di Giorgio S, Martignano F, Torcia MG, Mattiuz G, Conticello SG. Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2. Sci Adv. 2020;6(25):eabb5813. doi:10.1126/sciadv.abb5813
Ratcliff J, Simmonds P. Potential APOBEC-mediated RNA editing of the genomes of SARS-CoV-2 and other coronaviruses and its impact on their longer term evolution. Virology. 2021;556:62-72. doi:10.1016/j.virol.2020.12.018
Nakata Y, Ode H, Kubota M, et al. Cellular APOBEC3A deaminase drives mutations in the SARS-CoV-2 genome. Nucleic Acids Res. 2023;51(2):783-795. doi:10.1093/nar/gkac1238
Sheehy AM, Gaddis NC, Choi JD, Malim MH. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature. 2002;418(6898):646-650. doi:10.1038/nature00939
Sayers EW, Cavanaugh M, Clark K, et al. GenBank 2023 update. Nucleic Acids Res. 2023;51:D141-D144. doi:10.1093/nar/gkac1012
Khare S, Gurry C, Freitas L, et al. GISAID's role in pandemic response. China CDC Weekly. 2021;3(1049):1049-1051. doi:10.46234/ccdcw2021.255.