Int J Antimicrob Agents . Potential of Coronavirus 3C-like Protease Inhibitors for the Development of New anti-SARS-CoV-2 Drugs: Insights From Structures of Protease and Inhibitors

[tetano]

Int J Antimicrob Agents


. 2020 Jun 10;106055.
doi: 10.1016/j.ijantimicag.2020.106055. Online ahead of print.
Potential of Coronavirus 3C-like Protease Inhibitors for the Development of New anti-SARS-CoV-2 Drugs: Insights From Structures of Protease and Inhibitors


Jun He ¹ , Lijun Hu ² , Xiaojun Huang ² , Chenran Wang ² , Zhimin Zhang ³ , Ying Wang ² , Dongmei Zhang ⁴ , Wencai Ye ⁵



Affiliations

• PMID: 32534187
• DOI: 10.1016/j.ijantimicag.2020.106055

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV), which belong to the same β-coronavirus group, induces sever acute respiratory disease, threatening human health. Since the outbreak of SARS-CoV-2 infection began, the disease has rapidly spread worldwide. Thus, a search for effective drugs, able to inhibit the coronavirus, has become a global pursuit. The 3C-like protease (3CL^pro), which hydrolyzes the polyprotein to produce functional proteins, is essential for coronavirus replication and considered an important therapeutic target for diseases caused by coronaviruses, including coronavirus disease 2019 (COVID-19). Many 3CL^pro inhibitors have been proposed, and some new drug candidates have achieved success in preclinical studies. In this review, we briefly describe the recent developments in the structure of 3CL^pro and its function in coronavirus replication and summarize new insights into 3CL^pro inhibitors and their mechanisms of action. We also discuss the clinical application prospects and limitations of 3CL^pro inhibitors for COVID-19 treatment.

Keywords: 3C-like protease; 3CL(pro) inhibitor; COVID-19; Coronavirus; MERS; SARS.