Structural insight to hydroxychloroquine-3C-like proteinase complexation from SARS-CoV-2: inhibitor modelling study through molecular docking and MD-simulation study

Abstract

The spread of novel coronavirus strain, Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) causes Coronavirus disease (COVID-19) has now spread worldwide and effecting the entire human race. The viral genetic material is transcripted and replicated by 3 C-like protease, as a result, it is an important drug target for COVID-19. Hydroxychloroquine (HCQ) report promising results against this drug target so, we perform molecular docking followed by MD-simulation studies of HCQ and modelled some ligand (Mod-I and Mod-II) molecules with SARS-CoV-2-main protease which reveals the structural organization of the active site residues and presence of a conserve water-mediated catalytic triad that helps in the recognition of Mod-I/II ligand molecules. The study may be helpful to gain a detailed structural insight on the presence of water-mediated catalytic triad which could be useful for inhibitor modelling.

Communicated by Ramaswamy H. Sarma

Keywords:

• COVID-19
• SARS-CoV-2
• Hydroxychloroquine
• catalytic triad
• conserved water molecule

Acknowledgements

SM, SD, UA, and SSP acknowledge the National Institute of Technology (Government of India)–Durgapur for providing research facilities at the Department of Chemistry, NIT Durgapur. All the authors acknowledge Mr. Swarnendu Gupta for computational assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.