tetano
Editor, Senior Moderator
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[SUP]pro[/SUP] (main protease) or 3CL[SUP]pro[/SUP] (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[SUP]pro[/SUP] is highly conserved among various CoVs as the mutation in M[SUP]pro[/SUP] is often lethal to the virus. Thus, drugs targeting M[SUP]pro[/SUP] 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[SUP]pro[/SUP] 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[SUP]pro[/SUP] 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
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[SUP]pro[/SUP] (main protease) or 3CL[SUP]pro[/SUP] (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[SUP]pro[/SUP] is highly conserved among various CoVs as the mutation in M[SUP]pro[/SUP] is often lethal to the virus. Thus, drugs targeting M[SUP]pro[/SUP] 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[SUP]pro[/SUP] 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[SUP]pro[/SUP] 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