Plant Source Derived Compound Exhibited In Silico Inhibition of Membrane Glycoprotein In SARS-CoV-2: Paving the Way to Discover a New Class of Compound For Treatment of COVID-19

Saurov Mahanta; Tufan Naiya; Kunal Biswas; Liza Changkakoti; Yugal Kishore Mohanta; Bhaben Tanti; Awdhesh Kumar Mishra; Tapan Kumar Mohanta; Nanaocha Sharma

doi:10.3389/fphar.2022.805344

Plant Source Derived Compound Exhibited In Silico Inhibition of Membrane Glycoprotein In SARS-CoV-2: Paving the Way to Discover a New Class of Compound For Treatment of COVID-19

Front Pharmacol. 2022 Apr 7:13:805344. doi: 10.3389/fphar.2022.805344. eCollection 2022.

Authors

Saurov Mahanta¹, Tufan Naiya², Kunal Biswas³, Liza Changkakoti¹, Yugal Kishore Mohanta⁴, Bhaben Tanti⁵, Awdhesh Kumar Mishra⁶, Tapan Kumar Mohanta⁷, Nanaocha Sharma⁸

Affiliations

¹ National Institute of Electronics and Information Technology (NIELIT), Guwahati, India.
² Department of Biotechnology, Maulana Abul Kalam Azad University of Technology, West Bengal, India.
³ Centre for Nanoscience and Nanotechnology, Sathyabama Institute of Science and Technology, Chennai, India.
⁴ Department of Applied Biology, School of Biological Sciences, University of Science and Technology Meghalaya (USTM), Baridua, India.
⁵ Department of Botany, Gauhati University, Guwahati, India.
⁶ Department of Biotechnology, Yeungnam University, Gyeongsan, South Korea.
⁷ Natural and Medical Sciences Research Centre, University of Nizwa, Nizwa, Oman.
⁸ Institute of Bioresources and Sustainable Development, Imphal, India.

Abstract

SARS-CoV-2 is the virus responsible for causing COVID-19 disease in humans, creating the recent pandemic across the world, where lower production of Type I Interferon (IFN-I) is associated with the deadly form of the disease. Membrane protein or SARS-CoV-2 M proteins are known to be the major reason behind the lower production of human IFN-I by suppressing the expression of IFNβ and Interferon Stimulated Genes. In this study, 7,832 compounds from 32 medicinal plants of India possessing traditional knowledge linkage with pneumonia-like disease treatment, were screened against the Homology-Modelled structure of SARS-CoV-2 M protein with the objective of identifying some active phytochemicals as inhibitors. The entire study was carried out using different modules of Schrodinger Suite 2020-3. During the docking of the phytochemicals against the SARS-CoV-2 M protein, a compound, ZIN1722 from Zingiber officinale showed the best binding affinity with the receptor with a Glide Docking Score of -5.752 and Glide gscore of -5.789. In order to study the binding stability, the complex between the SARS-CoV-2 M protein and ZIN1722 was subjected to 50 ns Molecular Dynamics simulation using Desmond module of Schrodinger suite 2020-3, during which the receptor-ligand complex showed substantial stability after 32 ns of MD Simulation. The molecule ZIN1722 also showed promising results during ADME-Tox analysis performed using Swiss ADME and pkCSM. With all the findings of this extensive computational study, the compound ZIN1722 is proposed as a potential inhibitor to the SARS-CoV-2 M protein, which may subsequently prevent the immunosuppression mechanism in the human body during the SARS-CoV-2 virus infection. Further studies based on this work would pave the way towards the identification of an effective therapeutic regime for the treatment and management of SARS-CoV-2 infection in a precise and sustainable manner.

Keywords: SARS-CoV2; homology modelling; in silico; membrane glycoprotein; molecular dynamics; phyto-compound.