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Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing
Open accessAbstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19)1. The development of a vaccine is likely to take at least 12–18 months, and the typical timeline for approval of a new antiviral therapeutic agent can exceed 10 years. Thus, repurposing of known drugs could substantially accelerate the deployment of new therapies for COVID-19. Here we profiled a library of drugs encompassing approximately 12,000 clinical-stage or Food and Drug Administration (FDA)-approved small molecules to identify candidate therapeutic drugs for COVID-19. We report the identification of 100 molecules that inhibit viral replication of SARS-CoV-2, including 21 drugs that exhibit dose–response relationships. Of these, thirteen were found to harbour effective concentrations commensurate with probable achievable therapeutic doses in patients, including the PIKfyve kinase inhibitor apilimod2–4 and the cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825 and ONO 5334. Notably, MDL-28170, ONO 5334 and apilimod were found to antagonize viral replication in human pneumocyte-like cells derived from H9 human embryonic stem cell lines, and apilimod also demonstrated antiviral efficacy in a primary human lung explant model. Since most of the molecules identified in this study have already advanced into the clinic, their known pharmacological and human safety profiles will enable accelerated preclinical and clinical evaluation of these drugs for the treatment of COVID-19. A screen of the ReFRAME library of approximately 12,000 known drugs for antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identified several candidate compounds with suitable activities and pharmacological profiles, which could potentially expedite the deployment of therapies for coronavirus disease 2019 (COVID-19).
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Cited by
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Metadata
- Authors
- Riva, L., Yuan, S., Yin, X., Martin-Sancho, L., Matsunaga, N., Pache, L., Burgstaller-Muehlbacher, S., De Jesus, P. D., Teriete, P., Hull, M. V., Chang, M. W., Chan, J. F.-W., Cao, J., Poon, V. K.-M., Herbert, K. M., Cheng, K., Nguyen, T.-T. H., Rubanov, A., Pu, Y., Nguyen, C., Choi, A., Rathnasinghe, R., Schotsaert, M., Miorin, L., Dejosez, M., Zwaka, T. P., Sit, K.-Y., Martinez-Sobrido, L., Liu, W.-C., White, K. M., Chapman, M. E., Lendy, E. K., Glynne, R. J., Albrecht, R., Ruppin, E., Mesecar, A. D., Johnson, J. R., Benner, C., Sun, R., Schultz, P. G., Su, A. I., García-Sastre, A., Chatterjee, A. K., Yuen, K.-Y., & Chanda, S. K.
- Venue
- Nature
- Published
- 2020-07-24
- Volume
- 586
- Issue
- 7827
- Pages
- 113-119
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3044927477
- Cited by
- 760
- References
- 61
- FWCI
- 19.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Riva, L., Yuan, S., Yin, X., Martin-Sancho, L., Matsunaga, N., Pache, L., Burgstaller-Muehlbacher, S., De Jesus, P. D., Teriete, P., Hull, M. V., Chang, M. W., Chan, J. F.-W., Cao, J., Poon, V. K.-M., Herbert, K. M., Cheng, K., Nguyen, T.-T. H., Rubanov, A., Pu, Y., . . . Chanda, S. K. (2020). Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing. Nature. https://doi.org/10.1038/s41586-020-2577-1
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