Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 46, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2021.116301
Keywords
SARS-CoV; Coronavirus; 3CLpro; Peptidomimetic inhibitors (PIs); Small-molecule inhibitors (SMIs); Organic synthesis; Medicinal chemistry
Funding
- All-India Council for Technical Education (AICTE), New Delhi, India (AICTENDF)
- All-India Council for Technical Education (AICTE), New Delhi, India
- RUSA 2.0 of University Grants Commission (UGC), New Delhi
- Department of Pharmaceutical Technology, Jadavpur University, Kolkata
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Severe Acute Respiratory Syndrome (SARS) and COVID-19 are caused by different strains of coronaviruses, with SARS-CoV and SARS-CoV-2 playing significant roles in the viral life cycle and disease development. The study focuses on the development and analysis of potential inhibitors targeting the viral proteinase, which could lead to effective treatments for coronaviruses in the future. The research provides insights into the synthesis and interaction of various inhibitors with 3CLpro, highlighting promising candidates for further exploration in the development of antiviral drugs.
Severe Acute Respiratory Syndrome (SARS) is a severe febrile respiratory disease caused by the beta genus of human coronavirus, known as SARS-CoV. Last year, 2019-n-CoV (COVID-19) was a global threat for everyone caused by the outbreak of SARS-CoV-2. 3CLpro, chymotrypsin-like protease, is a major cysteine protease that substantially contributes throughout the viral life cycle of SARS-CoV and SARS-CoV-2. It is a prospective target for the development of SARS-CoV inhibitors by applying a repurposing strategy. This review focuses on a detailed overview of the chemical synthesis and computational chemistry perspectives of peptidomimetic inhibitors (PIs) and small-molecule inhibitors (SMIs) targeting viral proteinase discovered from 2004 to 2020. The PIs and SMIs are one of the primary therapeutic inventions for SARS-CoV. The journey of different analogues towards the evolution of SARS-CoV 3CLpro inhibitors and complete synthetic preparation of nineteen derivatives of PIs and ten derivatives of SMIs and their computational chemistry perspectives were reviewed. From each class of de-rivatives, we have identified and highlighted the most compelling PIs and SMIs for SARS-CoV 3CLpro. The protein-ligand interaction of 29 inhibitors were also studied that involved with the 3CLpro inhibition, and the frequent amino acid residues of the protease were also analyzed that are responsible for the interactions with the inhibitors. This work will provide an initiative to encourage further research for the development of effective and drug-like 3CLpro inhibitors against coronaviruses in the near future.
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