Progress on SARS-CoV-2 3CLpro Inhibitors: Inspiration from SARS-CoV 3CLpro Peptidomimetics and Small-Molecule Anti-Inflammatory Compounds

Abstract

Jiajie Zhu,1,* Haiyan Zhang,2,* Qinghong Lin,1 Jingting Lyu,1 Lu Lu,1 Hanxi Chen,1 Xuning Zhang,1 Yanjun Zhang,3 Keda Chen3 1Shulan International Medical College, Zhejiang Shuren University, Hangzhou, People’s Republic of China; 2Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Keda Chen; Yanjun Zhang, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, People’s Republic of China, Tel +8615068129828 ; +8613858115856, Fax +86057188280783, Email [email protected]; [email protected]: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently poses a threat to human health. 3C-like proteinase (3CLpro) plays an important role in the viral life cycle. Hence, it is considered an attractive antiviral target protein. Whole-genome sequencing showed that the sequence homology between SARS-CoV-2 3CLpro and SARS-CoV 3CLpro is 96.08%, with high similarity in the substrate-binding region. Thus, assessing peptidomimetic inhibitors of SARS-CoV 3CLpro could accelerate the development of peptidomimetic inhibitors for SARS-CoV-2 3CLpro. Accordingly, we herein discuss progress on SARS-CoV-2 3CLpro peptidomimetic inhibitors. Inflammation plays a major role in the pathophysiological process of COVID-19. Small-molecule compounds targeting 3CLpro with both antiviral and anti-inflammatory effects are also briefly discussed in this paper.Keywords: SARS-CoV, SARS-CoV-2, 3CLpro, peptidomimetics, anti-inflammatory agents, small-molecule inhibitors, protease inhibitors

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