Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease
Lifeng Fu, Fei Ye, Yong Feng, Feng Yu, Qisheng Wang, Yan Wu, Cheng Zhao, Huan Sun, Baoying Huang, Peihua Niu, Hao Song, Yi Shi, Xuebing Li, Wenjie Tan, Jianxun Qi & George Fu Gao
Nature Communications volume 11, Article number: 4417 (2020)
Abstract
COVID-19 was declared a pandemic on March 11 by WHO, due to its great threat to global public health. The coronavirus main protease (Mpro, 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 Mpro. 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 Mpro 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.
