ACS Comb Sci. Targeting the dimerization of main protease of coronaviruses: A potential broad-spectrum therapeutic strategy

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ACS Comb Sci. 2020 May 13. doi: 10.1021/acscombsci.0c00058. [Epub ahead of print]
Targeting the dimerization of main protease of coronaviruses: A potential broad-spectrum therapeutic strategy.


Goyal B, Goyal D.

Abstract

A new coronavirus (CoV) caused a pandemic COVID-19, which has become a global health care emergency in the present date. The virus has been termed as SARS-CoV-2 (Severe Acute Respiratory Syndrome-Cororavirus-2) and has a genome similar (~82%) to the SARS-CoV (SARS coronavirus). An attractive therapeutic target for CoVs is the M^pro (main protease) or 3CL^pro (3-chymotrypsin-like cysteine protease) as the enzyme plays a key role in the polyprotein processing and is active in a dimeric form. Further, M^pro is highly conserved among various CoVs as the mutation in M^pro is often lethal to the virus. Thus, drugs targeting M^pro enzyme significantly reduce the risk of mutation-mediated drug resistance and display broad-spectrum antiviral activity. The combinatorial design of peptide-based inhibitors targeting the dimerization of SARS-CoV M^pro represent a potential therapeutic strategy. In this regard, we compiled the literature reports highlighting the effect of mutations and N-terminal deletion of residues of SARS-CoV M^pro on its dimerization and thus, catalytic activity. We believe that the present review will stimulate research in this less explored, yet quite significant area. The effect of the COVID-19 epidemic and the possibility of future CoV outbreaks strongly emphasize the urgent need for the design and development of potent antiviral agents against CoV infections.



PMID:32402186DOI:10.1021/acscombsci.0c00058