This review summarizes the structural features, substrate specificity, and inhibitor binding modes of 12 coronavirus 3C-like proteases to guide future structure-based antiviral drug discovery.
This review provides a comprehensive understanding of CoV 3CL protease structures and inhibitor binding modes to guide future antiviral drug discovery.
Abstract The emergence of a variety of coronaviruses (CoVs) in the last decades has posed huge threats to human health. Especially, the ongoing pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has led to more than 70 million infections and over 1.6 million of deaths worldwide in the past few months. None of the efficacious antiviral agents against human CoVs have been approved yet. 3C‐like protease (3CL pro ) is an attractive target for antiviral intervention due to its essential role in processing polyproteins translated from viral RNA, and its conserved structural feature and substrate specificity among CoVs in spite of the sequence variation. This review focuses on all available crystal structures of 12 CoV 3CL pro s and their inhibitors, and intends to provide a comprehensive understanding of this protease from multiple aspects including its structural features, substrate specificity, inhibitor binding modes, and more importantly, to recapitulate the similarity and diversity among different CoV 3CL pro s and the structure–activity relationship of various types of inhibitors. Such an attempt could gain a deep insight into the inhibition mechanisms and drive future structure‐based drug discovery targeting 3CL pro s.
Xiong et al. (2021) conducted a review in Coronavirus disease 2019 (COVID-19) / Coronaviruses. 3C-like protease (3CL pro) inhibitors was evaluated. This review summarizes the structural features, substrate specificity, and inhibitor binding modes of 12 coronavirus 3C-like proteases to guide future structure-based antiviral drug discovery.