The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
The mechanism of resistance to favipiravir in influenza
Open accessAbstract
Favipiravir is a broad-spectrum antiviral that has shown promise in treatment of influenza virus infections. While emergence of resistance has been observed for many antiinfluenza drugs, to date, clinical trials and laboratory studies of favipiravir have not yielded resistant viruses. Here we show evolution of resistance to favipiravir in the pandemic H1N1 influenza A virus in a laboratory setting. We found that two mutations were required for robust resistance to favipiravir. We demonstrate that a K229R mutation in motif F of the PB1 subunit of the influenza virus RNA-dependent RNA polymerase (RdRP) confers resistance to favipiravir in vitro and in cell culture. This mutation has a cost to viral fitness, but fitness can be restored by a P653L mutation in the PA subunit of the polymerase. K229R also conferred favipiravir resistance to RNA polymerases of other influenza A virus strains, and its location within a highly conserved structural feature of the RdRP suggests that other RNA viruses might also acquire resistance through mutations in motif F. The mutations identified here could be used to screen influenza virus-infected patients treated with favipiravir for the emergence of resistance.
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Cites
Favipiravir (T-705), a novel viral RNA polymerase inhibitor
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Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase
FURUTA, Y., KOMENO, T., & NAKAMURA, T. (2017) · Proceedings of the Japan Academy, Series B · doi:10.2183/pjab.93.027 · Cited by 1,070
Bright, R. A. (2006) · JAMA · doi:10.1001/jama.295.8.joc60020 · Cited by 671
Permissive Secondary Mutations Enable the Evolution of Influenza Oseltamivir Resistance
Bloom, J. D., Gong, L. I., & Baltimore, D. (2010) · Science · doi:10.1126/science.1187816 · Cited by 649
Mechanism of Action of T-705 against Influenza Virus
Furuta, Y., Takahashi, K., Kuno-Maekawa, M., Sangawa, H., Uehara, S., Kozaki, K., Nomura, N., Egawa, H., & Shiraki, K. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.3.981-986.2005 · Cited by 546
In Vitro and In Vivo Activities of Anti-Influenza Virus Compound T-705
Furuta, Y., Takahashi, K., Fukuda, Y., Kuno, M., Kamiyama, T., Kozaki, K., Nomura, N., Egawa, H., Minami, S., Watanabe, Y., et al. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.4.977-981.2002 · Cited by 501
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Structure of influenza A polymerase bound to the viral RNA promoter
Pflug, A., Guilligay, D., Reich, S., & Cusack, S. (2014) · Nature · doi:10.1038/nature14008 · Cited by 481
Pfeiffer, J. K., & Kirkegaard, K. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1232294100 · Cited by 404
Favipiravir as a potential countermeasure against neglected and emerging RNA viruses
Delang, L., Abdelnabi, R., & Neyts, J. (2018) · Antiviral Research · doi:10.1016/j.antiviral.2018.03.003 · Cited by 388
Cited by
Guo (2020) · doi:10.1186/s40779-020-00240-0 · Cited by 4,735
Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial
Chen, C., Zhang, Y., Huang, J., Yin, P., Cheng, Z., Wu, J., Chen, S., Zhang, Y., Chen, B., Lu, M., et al. (2020) · doi:10.1101/2020.03.17.20037432 · Cited by 852
“promising antiviral drug targeting the influenza viral RNA-dependent RNA polymerase (RdRP) [6].”
BackgroundOvsyannikova, I. G., Haralambieva, I. H., Crooke, S. N., Poland, G. A., & Kennedy, R. B. (2020) · Immunological Reviews · doi:10.1111/imr.12897 · Cited by 258
Tuccori, M., Convertino, I., Ferraro, S., Cappello, E., Valdiserra, G., Focosi, D., & Blandizzi, C. (2020) · Drug Safety · doi:10.1007/s40264-020-00965-w · Cited by 80
Metadata
- Authors
- Goldhill, D. H., te Velthuis, A. J. W., Fletcher, R. A., Langat, P., Zambon, M., Lackenby, A., & Barclay, W. S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2018-10-23
- Volume
- 115
- Issue
- 45
- Pages
- 11613-11618
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2895861302
- Cited by
- 298
- References
- 36
- FWCI
- 28.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Goldhill, D. H., te Velthuis, A. J. W., Fletcher, R. A., Langat, P., Zambon, M., Lackenby, A., & Barclay, W. S. (2018). The mechanism of resistance to favipiravir in influenza. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1811345115
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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