COVID-19 was declared a pandemic on March 11 by WHO, due to its great threat to global public health. The coronavirus main protease (M pro , also called 3CLpro) is essential for processing and maturation of the viral polyprotein, therefore recognized as an attractive drug target. Here we show that a clinically approved anti-HCV drug, Boceprevir, and a pre-clinical inhibitor against feline infectious peritonitis (corona) virus (FIPV), GC376, both efficaciously inhibit SARS-CoV-2 in Vero cells by targeting M pro . Moreover, combined application of GC376 with Remdesivir, a nucleotide analogue that inhibits viral RNA dependent RNA polymerase (RdRp), results in sterilizing additive effect. Further structural analysis reveals binding of both inhibitors to the catalytically active side of SARS-CoV-2 protease M pro as main mechanism of inhibition. Our findings may provide critical information for the optimization and design of more potent inhibitors against the emerging SARS-CoV-2 virus. Coronavirus main protease is essential for viral polyprotein processing and maturation. Here Fu et al. report efficient inhibition of SARS-CoV-2 replication using two inhibitors – Boceprevir and GC376 – targeting the active site of the main viral protease.
【저자키워드】 SARS-CoV-2, High-throughput screening, Proteases, Nanocrystallography, 【초록키워드】 COVID-19, coronavirus, pandemic, SARS-CoV-2 virus, 3CLpro, protease, virus, drug target, RdRP, WHO, Viral RNA, RNA polymerase, inhibitor, information, Critical, SARS-CoV-2 replication, mechanism, binding, boceprevir, nucleotide, Structural analysis, Anti-HCV, maturation, global public health, SARS-CoV-2 protease, M pro, polyprotein, Vero Cell, clinically, inhibit, approved, reveal, catalytically active, inhibit SARS-CoV-2, 【제목키워드】 protease, boceprevir, inhibit SARS-CoV-2,