Molecular Modeling of Isolated Phytochemicals from Ocimum sanctum Towards Exploring Potential Inhibitors of SARS Coronavirus Main Protease and Papain-Like Protease to Treat COVID-19

Abstract

Background: In December 2019, there was a cluster of pneumonia cases in China. Investigations found that it was caused by a previously unknown virus, now named the 2019 Novel Coronavirus (CoV). CoV are a large group of viruses; they consist of a core of genetic material surrounded by an envelope of proteins spikes. There are different types of CoV that causes respiratory and sometimes gastrointestinal symptoms. Respiratory symptoms can range from the common cold to pneumonia and in most people the symptoms tend to be mild. However, there are some types of CoV that can cause severe disease, these include SARS - CoV, identified in China 2003, and MERS - CoV, that was first identified in Saudi Arabia in 2012. The 2019 CoV was first identified in China 2019. Currently 146, 305 cases has been reported for CoV included 5441 case for death, widely. To overcome this epidemiology, investigator find CoV main protease and papain-like protease, which plays a pivotal role in viral gene expression and replication through the proteolytic processing of replicase polyproteins, is an attractive target for anti-CoV drug design.

Methods: For the conduction of work, a Crystal structure SARS-CoV-2 (2019-nCoV) main protease, SARS CoV papain-like protease, and SARS Spike Glycoprotein - human ACE2 were downloaded from RCSB protein data bank and further isolated by using Chimera. Docking studies were performed to assess binding affinities between isolated receptor and 7 phytophenolic compounds. Molecular dynamic simulation were done to investigate the most stable receptor-ligand complex.

Results: The docking results were evaluated based on free energies of binding (ΔG) and result suggested tulsinol A, B, C, D, E, F, G, and dihydrodieuginol B inhibitors of SARS Coronavirus Main Protease and Papain-like Protease.

Conclusion: Based on the molecular simulation study, we may conclude that Ocimum sanctum extract can be included as a preventive measure against CoV due to its potential to inhibit replication of CoV supported with its immunomodulatory feature and ACE II blocking properties. Our findings give an approach to explore and discover the structure-based drug designing in the development of newer drug moieties and be a help against the widespread of COVID-19.

Keywords: Molecular modeling, Coronavirus, Viral protease, Virus replication, ACE2