In silico study to evaluate the antiviral activity of novel structures against 3c-like protease of novel coronavirus (Covid-19) and sars-cov

Kiran Chunduru, Runali Sankhe, Farmiza Begum, Nalini Sodum, Nitesh Kumar, Anoop Kishore, Rekha R. Shenoy, C. Mallikarjuna Rao, Kavitha Saravu

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Background: Globally, over 4.3 million laboratory confirmed cases of COVID-19 have been reported from over 105 countries. No FDA approved antiviral is available for the treatment of this infection. Zhavoronkov et al., with their generative chemistry pipeline, have generated structures that can be potential novel drug-like inhibitors for COVID-19, provided they are validated. 3C–like protease (3CLP) is a homodimeric cysteine protease that is present in coronaviruses. Interestingly, 3CLP is 96.1% structurally similar between SARS-CoV and SARS-CoV-2. Objective: To evaluate interaction of generated structures with 3CLP of SARS-CoV (RCSB PDB ID: 4MDS). Methods: Crystal structure of human SARS-CoV with a non-covalent inhibitor with resolution: 1.598 Å was obtained and molecular docking was performed to evaluate the interaction with generated structures. The MM-GBSA and IFD-SP were performed to narrow down to the structures with better binding energy and IFD score. The ADME analysis was performed on top 5 hits and further MD simulation was employed for top 2 hits. Results: In XP docking, IFD-SP and molecular dynamic simulation studies, the top 2 hits 32 and 61 showed interaction with key amino acid residue GLU166. Structure 61, also showed interaction with HIS164. These interactions of generated structure 32 and 61, with GLU166 and HIS164, indicate the binding of the selected drug within the close proximity of 3CLP. In the MD simulation, the protein– ligand complex of 4MDS and structure 61 was found to be more stable for 10ns. Conclusion: These identified structures can be further assessed for their antiviral activity to combat SARS-CoV and COVID-19.

Original languageEnglish
Pages (from-to)380-395
Number of pages16
JournalMedicinal Chemistry
Issue number4
Publication statusPublished - 2021

All Science Journal Classification (ASJC) codes

  • Drug Discovery


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