Targeting the Dimerization of the Main Protease of Coronaviruses: A Potential Broad-Spectrum Therapeutic Strategy

被引:251
作者
Goyal, Bhupesh [1 ]
Goyal, Deepti [2 ]
机构
[1] Thapar Inst Engn & Technol, Sch Chem & Biochem, Patiala 147004, Punjab, India
[2] Sri Guru Granth Sahib World Univ, Fac Basic & Appl Sci, Dept Chem, Fatehgarh Sahib 140406, Punjab, India
关键词
3CL(pro); broad-spectrum antiviral agents; coronavirus; COVID-19; dimerization; homodimer; main protease (M-pro); mutation; SARS-CoV; SARS-CoV-2; RESPIRATORY-SYNDROME-CORONAVIRUS; SARS-CORONAVIRUS; MOLECULAR-DYNAMICS; 3C-LIKE PROTEASE; DIMER INTERFACE; DRUG DISCOVERY; PROTEINASE; MECHANISM; DISSOCIATION; INHIBITORS;
D O I
10.1021/acscombsci.0c00058
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
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 (similar to 82%) to that of the previously known SARS-CoV (SARS coronavirus). An attractive therapeutic target for CoVs is the main protease (M-pro) or 3-chymotrypsin-like cysteine protease (3CL(pro)), as this enzyme plays a key role in polyprotein processing and is active in a dimeric form. Further, M-pro is highly conserved among various CoVs, and a mutation in M-pro is often lethal to the virus. Thus, drugs targeting the 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 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 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.
引用
收藏
页码:297 / 305
页数:9
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