Year: 2020
Type: preprint
Abstract: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has led to over 200,000 deaths thus far. We screened a library of approved antiviral drugs against the two SARS-CoV-2 proteases, 3C-like/main protease (3CLpro/Mpro) and papain-like protease (PLpro), which are essential for viral replication and attractive drug targets. Three HCV protease inhibitors were tested and found to inhibit 3CLpro and PLpro enzymes from Alpha-, Beta- and Gamma-coronaviruses. Anti-HIV drugs had no activity. Boceprevir and telaprevir inhibited 3CLpro, with boceprevir inhibiting eight of nine coronavirus 3CLpro enzymes tested including from SARS-CoV-2, MERS and SARS-CoV. Asunaprevir inhibited PLpro from SARS-CoV-2 and four other coronaviruses. The 1.4 Å X-ray structure of boceprevir bound to 3CLpro was determined to explain its broad-spectrum activity and guide structure-based design of inhibitors of multiple coronaviruses.Authors Brandon J. Anson, Mackenzie E. Chapman, and Emma K. Lendy contributed equally to this work.
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Energy, U.S. Department of Health and Human Services, Michigan Economic Development Corporation, Ministerio de Economía y Competitividad, National Institutes of Health, Office of Science, Michigan Technology Tri-Corridor, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Argonne National Laboratory
Awards: G102163711, G107546177, G1313983767, G1505794299, G1664757510, G1947107004, G2101401529, G2287611682, G262962599, G2887060908, G2896567508, G3075337988, G3329398301, G340565428, G409777406, G416541740, G4222258032, G4345827571, G4773269573, G498139845, G5106849484, G533379926, G5607048534, G5906309288, G6101244626, G6848031779, G6918803902, G7147508703, G7368700025, G816767278, G8500532866, Mechanisms of viral proteases in coronavirus replication and pathogenesis, G8764064047, Purdue Molecular Biophysics Training Program, G969889393, G993149817
OpenAlex ID: W3118795774