Identification of novel potential inhibitor of thymidylate kinase from Variola virus

Abstract

A hit compound was designed using Fragment Based Drug Designing (FBDD) approach, density functional theory (DFT) calculations were performed to find the structural and electronic properties. Additionally, pharmacokinetic properties were studied to understand the biological response of the compound. Docking studies were carried out with the protein structure of VrTMPK and HssTMPK with the reported hit compound. The favored docked complex was further carried to perform MD simulations; the RMSD plot and H-bond analysis was done for 200 ns. Also, MM-PBSA was done to understand the binding energy constituents and stability of the complex. A comparative study of the designed hit compound was done with FDA approved Tecovirimat. As a result, it was found that the reported compound (POX-A)is a potential selective inhibitor for Variola virus. Hence, it can be used to study further in vivo and in vitro behavior of the compound.

Communicated by Ramaswamy H. Sarma

Keywords:

• Monkeypox
• Variola virus
• thymidylate kinase
• molecular docking
• molecular dynamics

Acknowledgments

Author, Prashasti Sinha is very thankful to the University Grant Commission (UGC), New Delhi, India, for the financial support for doctoral research work. Authors would like to acknowledge IIT Delhi, India for allowing the access of SCFBio web server.

Data availability statement

All the relevant data is given in the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work received no external funding.