In Silico Identification of Small Molecules as Novel Coronavirus Protease Enzyme Inhibitors

Abstract

Abstract

The novel corona virus 2019 (COVID-19) is one of the global threats to the human civilization as it causes serious respiratory infection and multi-organ failure. Because of the absence of appropriate treatment protocol for 2019 novel corona virus, different methodologies are being tried in China, including drug repurposing. Recent discovery revealed the structure of novel corona virus main protease enzyme (M^pro) containing HIS41 and CYS145 amino acid residues present in catalytic domain, play crucial role in viral reproduction. Which facilities a promising approach to develop a new drug against COVID-19.  Therefore, successive inhibition of protease enzyme through a small molecular chemical analogue can be an effective approach to prevent the 2019 novel corona virus infection. In the present study, undertaking virtual screening approach-based screening of small molecule library was performed with the main protease enzyme protein of SARS CoV2. N-napthalen-1-yl methyl-2’-[3,5-dimethoxybenzamido]-2’deoxy-adenosine (DB03331)was identified as a small molecule showing satisfactory binding with this main protease enzyme. Physiochemical and pharmacokinetic assessment of proposed analogue was observed, which indicate, that the drug has suitable absorption, distribution, metabolism and elimination (ADME) profile. A 100 ns molecular dynamics was performed to analyze the stability of main protease-ligand complex. The RMSD and RMSF value indicate that the protease protein retains approximate stability after binding with the proposed analogue. However, further studies are required to perform   to evaluate the SARS CoV2 main protease inhibitory activity by conducting in-vitro and in-vivo study. In future, the proposed small molecule protease inhibitor analogue can be used for the therapy of COVID-19.

Keywords: COVID-19, main protease enzyme(M^pro), Molecular docking, Molecular dynamics

Cite this Article

Arkadeep Sarkar, Arghya Banik, Trambak Basak, Barun Dasgupta. In Silico Identification of Small Molecules as Novel Coronavirus Protease Enzyme Inhibitors. Research & Reviews: A Journal of Bioinformatics. 2020; 7(2): 33–43p.