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Targeting the Dimerization of the Main Protease of Coronaviruses: A Potential Broad-Spectrum Therapeutic Strategy.
ACS Comb Sci. 2020 06 08; 22(6):297-305.AC

Abstract

A new coronavirus (CoV) caused a pandemic named COVID-19, which has become a global health care emergency in the present time. The virus is referred to as SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) and has a genome similar (∼82%) to that of the previously known SARS-CoV (SARS coronavirus). An attractive therapeutic target for CoVs is the main protease (Mpro) or 3-chymotrypsin-like cysteine protease (3CLpro), as this enzyme plays a key role in polyprotein processing and is active in a dimeric form. Further, Mpro is highly conserved among various CoVs, and a mutation in Mpro is often lethal to the virus. Thus, drugs targeting the Mpro 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 Mpro represents a potential therapeutic strategy. In this regard, we have compiled the literature reports highlighting the effect of mutations and N-terminal deletion of residues of SARS-CoV Mpro 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.

Authors+Show Affiliations

School of Chemistry & Biochemistry, Thapar Institute of Engineering & Technology, Patiala-147004, Punjab, India.Department of Chemistry, Faculty of Basic and Applied Sciences, Sri Guru Granth Sahib World University, Fatehgarh Sahib-140406, Punjab, India.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32402186

Citation

Goyal, Bhupesh, and Deepti Goyal. "Targeting the Dimerization of the Main Protease of Coronaviruses: a Potential Broad-Spectrum Therapeutic Strategy." ACS Combinatorial Science, vol. 22, no. 6, 2020, pp. 297-305.
Goyal B, Goyal D. Targeting the Dimerization of the Main Protease of Coronaviruses: A Potential Broad-Spectrum Therapeutic Strategy. ACS Comb Sci. 2020;22(6):297-305.
Goyal, B., & Goyal, D. (2020). Targeting the Dimerization of the Main Protease of Coronaviruses: A Potential Broad-Spectrum Therapeutic Strategy. ACS Combinatorial Science, 22(6), 297-305. https://doi.org/10.1021/acscombsci.0c00058
Goyal B, Goyal D. Targeting the Dimerization of the Main Protease of Coronaviruses: a Potential Broad-Spectrum Therapeutic Strategy. ACS Comb Sci. 2020 06 8;22(6):297-305. PubMed PMID: 32402186.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeting the Dimerization of the Main Protease of Coronaviruses: A Potential Broad-Spectrum Therapeutic Strategy. AU - Goyal,Bhupesh, AU - Goyal,Deepti, Y1 - 2020/05/27/ PY - 2020/5/14/pubmed PY - 2020/6/17/medline PY - 2020/5/14/entrez KW - 3CLpro KW - COVID-19 KW - SARS-CoV KW - SARS-CoV-2 KW - broad-spectrum antiviral agents KW - coronavirus KW - dimerization KW - homodimer KW - main protease (Mpro) KW - mutation SP - 297 EP - 305 JF - ACS combinatorial science JO - ACS Comb Sci VL - 22 IS - 6 N2 - A new coronavirus (CoV) caused a pandemic named COVID-19, which has become a global health care emergency in the present time. The virus is referred to as SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) and has a genome similar (∼82%) to that of the previously known SARS-CoV (SARS coronavirus). An attractive therapeutic target for CoVs is the main protease (Mpro) or 3-chymotrypsin-like cysteine protease (3CLpro), as this enzyme plays a key role in polyprotein processing and is active in a dimeric form. Further, Mpro is highly conserved among various CoVs, and a mutation in Mpro is often lethal to the virus. Thus, drugs targeting the Mpro 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 Mpro represents a potential therapeutic strategy. In this regard, we have compiled the literature reports highlighting the effect of mutations and N-terminal deletion of residues of SARS-CoV Mpro 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. SN - 2156-8944 UR - https://www.unboundmedicine.com/medline/citation/32402186/Targeting_the_Dimerization_of_the_Main_Protease_of_Coronaviruses:_A_Potential_Broad_Spectrum_Therapeutic_Strategy_ L2 - https://doi.org/10.1021/acscombsci.0c00058 DB - PRIME DP - Unbound Medicine ER -