In Vitro Efficacy of Antivirals and Monoclonal Antibodies against SARS-CoV-2 Omicron Lineages XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1
Andrei A Pochtovyi, Daria D Kustova, Andrei E Siniavin, Inna V Dolzhikova, Elena V Shidlovskaya, Olga G Shpakova, Lyudmila A Vasilchenko, Arina A Glavatskaya, Nadezhda A Kuznetsova, Anna A Iliukhina, Artem Y Shelkov, Olesia M Grinkevich, Andrei G Komarov, Denis Y Logunov, Vladimir A Gushchin, Alexander L Gintsburg
Vaccines, doi:10.3390/vaccines11101533
The spread of COVID-19 continues, expressed by periodic wave-like increases in morbidity and mortality. The reason for the periodic increases in morbidity is the emergence and spread of novel genetic variants of SARS-CoV-2. A decrease in the efficacy of monoclonal antibodies (mAbs) has been reported, especially against Omicron subvariants. There have been reports of a decrease in the efficacy of specific antiviral drugs as a result of mutations in the genes of non-structural proteins. This indicates the urgent need for practical healthcare to constantly monitor pathogen variability and its effect on the efficacy of preventive and therapeutic drugs. As part of this study, we report the results of the continuous monitoring of COVID-19 in Moscow using genetic and virological methods. As a result of this monitoring, we determined the dominant genetic variants and identified the variants that are most widespread, not only in Moscow, but also in other countries. A collection of viruses from more than 500 SARS-CoV-2 isolates has been obtained and characterized. The genetic lines XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1, representing the greatest concern, were identified among the dominant variants. We studied the in vitro efficacy of mAbs Tixagevimab + Cilgavimab (Evusheld), Sotrovimab, Regdanvimab, Casirivimab + Imdevimab (Ronapreve), and Bebtelovimab, as well as the specific antiviral drugs Remdesivir, Molnupiravir, and Nirmatrelvir, against these genetic lines. At the current stage of the COVID-19 pandemic, the use of mAbs developed against early SARS-CoV-2 variants has little prospect. Specific antiviral drugs retain their activity, but further monitoring is needed to assess the risk of their efficacy being reduced and adjust recommendations for their use.
Conflicts of Interest: The authors declare no conflict of interest.
References
Akimkin, Popova, Khafizov, Dubodelov, Ugleva et al., COVID-19: Evolution of the Pandemic in Russia. Report II: Dynamics of the Circulation of SARS-CoV-2 Genetic Variants, J. Mikrobiol. Epidemiol. Immunobiol,
doi:10.36233/0372-9311-295Baden, El Sahly, Essink, Kotloff, Frey et al., Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine, N. Engl. J. Med,
doi:10.1056/NEJMoa2035389Dubey, Choudhary, Kumar, Tomar, Emerging SARS-CoV-2 Variants: Genetic Variability and Clinical Implications, Curr. Microbiol,
doi:10.1007/s00284-021-02724-1Focosi, Maggi, Mcconnell, Casadevall, Very Low Levels of Remdesivir Resistance in SARS-COV-2 Genomes after 18 Months of Massive Usage during the COVID19 Pandemic: A GISAID Exploratory Analysis, Antivir. Res,
doi:10.1016/j.antiviral.2022.105247Fong, Rockett, Agius, Chandra, Johnson-Mckinnon et al., In Silico Detection of Drug Resistance Conferring Mutations in Subpopulations of SARS-CoV-2 Genomes, BMC Infect. Dis,
doi:10.1186/s12879-023-08236-6Godkov, Ogarkova, Gushchin, Kleymenov, Mazunina et al., Revaccination in Age-Risk Groups with Sputnik V Is Immunologically Effective and Depends on the Initial Neutralizing SARS-CoV-2 IgG Antibodies Level, Vaccines,
doi:10.3390/vaccines11010090Greasley, Noell, Plotnikova, Ferre, Liu et al., Structural Basis for the in Vitro Efficacy of Nirmatrelvir against SARS-CoV-2 Variants, J. Biol. Chem,
doi:10.1016/j.jbc.2022.101972Gushchin, Pochtovyi, Kustova, Ogarkova, Tarnovetskii et al., Dynamics of SARS-CoV-2 Major Genetic Lineages in Moscow in the Context of Vaccine Prophylaxis, Int. J. Mol. Sci,
doi:10.3390/ijms232314670Imai, Ito, Kiso, Yamayoshi, Uraki et al., Efficacy of Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB, N. Engl. J. Med,
doi:10.1056/NEJMc2214302Jochmans, Liu, Donckers, Stoycheva, Boland et al., The Substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro Are Selected by a Protease Inhibitor In Vitro and Confer Resistance to Nirmatrelvir, mBio,
doi:10.1128/mbio.02815-22Klink, Safina, Nabieva, Shvyrev, Garushyants et al., The Rise and Spread of the SARS-CoV-2 AY.122 Lineage in Russia, Virus Evol,
doi:10.1093/ve/veac017Kurhade, Zou, Xia, Liu, Chang et al., Low Neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1 and XBB.1 by Parental mRNA Vaccine or a BA.5 Bivalent Booster, Nat. Med,
doi:10.1038/s41591-022-02162-xLan, Ge, Yu, Shan, Zhou et al., Structure of the SARS-CoV-2 Spike Receptor-Binding Domain Bound to the ACE2 Receptor, Nature,
doi:10.1038/s41586-020-2180-5Lau, Cheng, Leung, Lee, Hachim et al., Real-World COVID-19 Vaccine Effectiveness against the Omicron BA.2 Variant in a SARS-CoV-2 Infection-Naive Population, Nat. Med,
doi:10.1038/s41591-023-02219-5Logunov, Dolzhikova, Shcheblyakov, Tukhvatulin, Zubkova et al., Safety and Efficacy of an rAd26 and rAd5 Vector-Based Heterologous Prime-Boost COVID-19 Vaccine: An Interim Analysis of a Randomised Controlled Phase 3 Trial in Russia, Lancet,
doi:10.1016/S0140-6736(21)00234-8Miteva, Kitanova, Batselova, Lazova, Chervenkov et al., The End or a New Era of Development of SARS-CoV-2 Virus: Genetic Variants Responsible for Severe COVID-19 and Clinical Efficacy of the Most Commonly Used Vaccines in Clinical Practice, Vaccines,
doi:10.3390/vaccines11071181Moeller, Passow, Harki, Aihara, SARS-CoV-2 nsp14 Exoribonuclease Removes the Natural Antiviral 3 -Deoxy-3 ,4 -Didehydro-Cytidine Nucleotide from RNA, Viruses,
doi:10.3390/v14081790Pinto, Park, Beltramello, Walls, Tortorici et al., Cross-Neutralization of SARS-CoV-2 by a Human Monoclonal SARS-CoV Antibody, Nature,
doi:10.1038/s41586-020-2349-yPlanas, Bruel, Staropoli, Guivel-Benhassine, Porrot et al., Resistance of Omicron Subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to Neutralizing Antibodies, Nat. Commun,
doi:10.1038/s41467-023-36561-6Polack, Thomas, Kitchin, Absalon, Gurtman et al., Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine, N. Engl. J. Med,
doi:10.1056/NEJMoa2034577Rognes, Flouri, Nichols, Quince, Mahé et al., A Versatile Open Source Tool for Metagenomics, PeerJ,
doi:10.7717/peerj.2584Shah, Woo, Omicron: A Heavily Mutated SARS-CoV-2 Variant Exhibits Stronger Binding to ACE2 and Potently Escapes Approved COVID-19 Therapeutic Antibodies, Front. Immunol,
doi:10.3389/fimmu.2021.830527Siniavin, Streltsova, Nikiforova, Kudryavtsev, Grinkina et al., Snake Venom Phospholipase A2s Exhibit Strong Virucidal Activity against SARS-CoV-2 and Inhibit the Viral Spike Glycoprotein Interaction with ACE2, Cell. Mol. Life Sci,
doi:10.1007/s00018-021-03985-6Stevens, Pruijssers, Lee, Gordon, Tchesnokov et al., Mutations in the SARS-CoV-2 RNA-Dependent RNA Polymerase Confer Resistance to Remdesivir by Distinct Mechanisms, Sci. Transl. Med,
doi:10.1126/scitranslmed.abo0718Uraki, Ito, Kiso, Yamayoshi, Iwatsuki-Horimoto et al., Antiviral and Bivalent Vaccine Efficacy against an Omicron XBB.1.5 Isolate, Lancet Infect. Dis,
doi:10.1016/S1473-3099(23)00070-1Voysey, Clemens, Madhi, Weckx, Folegatti et al., Safety and Efficacy of the ChAdOx1 nCoV-19 Vaccine (AZD1222) against SARS-CoV-2: An Interim Analysis of Four Randomised Controlled Trials in Brazil, South Africa, and the UK, Lancet,
doi:10.1016/S0140-6736(20)32661-1Xie, Edwards, Adam, Leung, Tsang et al., Resurgence of Omicron BA.2 in SARS-CoV-2 Infection-Naive Hong Kong, Nat. Commun,
doi:10.1038/s41467-023-38201-5Yamasoba, Uriu, Plianchaisuk, Kosugi, Pan et al., Virological Characteristics of the SARS-CoV-2 Omicron XBB.1.16 Variant, Lancet Infect. Dis,
doi:10.1016/S1473-3099(23)00278-5Yazawa, Yamazaki, Saga, Itamochi, Inasaki et al., Evaluation of SARS-CoV-2 Isolation in Cell Culture from Nasal/nasopharyngeal Swabs or Saliva Specimens of Patients with COVID-19, Sci. Rep,
doi:10.1038/s41598-023-35915-w
