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Robust classification-based molecular modelling of diverse chemical entities as potential SARS-CoV-2 3CLpro inhibitors: theoretical justification in light of experimental evidences.
Adhikari, N; Banerjee, S; Baidya, S K; Ghosh, B; Jha, T.
  • Adhikari N; Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
  • Banerjee S; Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
  • Baidya SK; Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
  • Ghosh B; Department of Pharmacy, BITS-Pilani, Hyderabad, India.
  • Jha T; Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
SAR QSAR Environ Res ; 32(6): 473-493, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1236142
ABSTRACT
COVID-19 is the most unanticipated incidence of 2020 affecting the human population worldwide. Currently, it is utmost important to produce novel small molecule anti-SARS-CoV-2 drugs urgently that can save human lives globally. Based on the earlier SARS-CoV and MERS-CoV infection along with the general characters of coronaviral replication, a number of drug molecules have been proposed. However, one of the major limitations is the lack of experimental observations with different drug molecules. In this article, 70 diverse chemicals having experimental SARS-CoV-2 3CLproinhibitory activity were accounted for robust classification-based QSAR analysis statistically validated with 4 different methodologies to recognize the crucial structural features responsible for imparting the activity. Results obtained from all these methodologies supported and validated each other. Important observations obtained from these analyses were also justified with the ligand-bound crystal structure of SARS-CoV-2 3CLpro enzyme. Our results suggest that molecules should contain a 2-oxopyrrolidine scaffold as well as a methylene (hydroxy) sulphonic acid warhead in proper orientation to achieve higher inhibitory potency against SARS-CoV-2 3CLpro. Outcomes of our study may be able to design and discover highly effective SARS-CoV-2 3CLpro inhibitors as potential anticoronaviral therapy to crusade against COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Protease Inhibitors / Coronavirus 3C Proteases / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Observational study / Prognostic study Language: English Journal: SAR QSAR Environ Res Journal subject: Environmental Health Year: 2021 Document Type: Article Affiliation country: 1062936x.2021.1914721

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Protease Inhibitors / Coronavirus 3C Proteases / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Observational study / Prognostic study Language: English Journal: SAR QSAR Environ Res Journal subject: Environmental Health Year: 2021 Document Type: Article Affiliation country: 1062936x.2021.1914721