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Potential Drugs Targeting Nsp16 Protein May Corroborates a Promising Approach to Combat SARSCoV-2 Virus

preprint
submitted on 11.05.2020 and posted on 13.05.2020 by Uma Shankar, Neha Jain, Prativa Majee, Subodh Kumar Mishra, Brijesh Rathi, Amit Kumar

The recent ongoing pandemic caused by SARS-CoV-2 continues to impose devastating impacts and is accountable for the loss of more than 250,000 human lives within a short span of four months. This urges immediate therapeutic measures to control the impact of this disease. One of the most conserved and potentially druggable sites is the Nsp16 active site that performs the 2’-O-methyltransferase activity and puts a 5’ cap on the viral RNA molecules. This allows them to mimic endogenous transcripts for the efficient translation of viral proteins and evasion of the immune response. Herein, we screened three libraries of compounds (>5500) with chemical diversity to identify hits against Nsp16 active site of SARS-CoV-2. From each library a top hit was identified, namely Velpatasvir from the FDA compounds; JFD00244 from the LOPAC library and compound 6 from the SAM based analog library. Interestingly, all three hits showed higher affinity than the positive controls. Velpatasvir is a known anti-viral drug used against Hepatitis C virus, and JFD00244 is a SIRT2 inhibitor. 100ns molecular simulation studies showed all three molecules to have stable and energetically favourable interactions with the active site of Nsp16. In summary, this investigation identified three potential drug candidates that are predicted to be potent Nsp16 inhibitors and could be pursued further in cell-based studies.

History

Email Address of Submitting Author

amitk@iiti.ac.in

Institution

Indian Institute of Technology, Indore

Country

India

ORCID For Submitting Author

0000-0002-5913-4308

Declaration of Conflict of Interest

The authors declare no competing financial interest.

Version Notes

MS Version 1

Exports