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Interface-based design of the favipiravir-binding site in SARS-CoV-2 RNA-dependent RNA polymerase reveals mutations conferring resistance to chain terminationстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Padhi A.K., Dandapat J., Saudagar P., Uversky V.N., Tripathi T.
- Журнал: FEBS Letters
- Том: 595
- Номер: 18
- Год издания: 2021
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: 2366
- Последняя страница: 2382
- Аннотация: Favipiravir is a broad-spectrum inhibitor of viral RNA-dependent RNA polymerase (RdRp) currently being used to manage COVID-19. Accumulation of mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RdRp may facilitate antigenic drift, generating favipiravir resistance. Focussing on the chain-termination mechanism utilized by favipiravir, we used high-throughput interface-based protein design to generate > 100 000 designs of the favipiravir-binding site of RdRp and identify mutational hotspots. We identified several single-point mutants and designs having a sequence identity of 97%-98% with wild-type RdRp, suggesting that SARS-CoV-2 can develop favipiravir resistance with few mutations. Out of 134 mutations documented in the CoV-GLUE database, 63 specific mutations were already predicted as resistant in our calculations, thus attaining ˜ 47% correlation with the sequencing data. These findings improve our understanding of the potential signatures of adaptation in SARS-CoV-2 against favipiravir.
- Добавил в систему: Уверский Владимир Николаевич