Druggability for COVID-19: in silico discovery of potential drug compounds against nucleocapsid (N) protein of SARS-CoV-2.

Manisha Ray,Saurav Sarkar,Surya Narayan Rath

doi:10.5808/gi.2020.18.4.e43

Abstract

The coronavirus disease 2019 is a contagious disease and had caused havoc throughout the world by creating widespread mortality and morbidity. The unavailability of vaccines and proper antiviral drugs encourages the researchers to identify potential antiviral drugs to be used against the virus. The presence of RNA binding domain in the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be a potential drug target, which serves multiple critical functions during the viral life cycle, especially the viral replication. Since vaccine development might take some time, the identification of a drug compound targeting viral replication might offer a solution for treatment. The study analyzed the phylogenetic relationship of N protein sequence divergence with other 49 coronavirus species and also identified the conserved regions according to protein families through conserved domain search. Good structural binding affinities of a few natural and/or synthetic phytocompounds or drugs against N protein were determined using the molecular docking approaches. The analyzed compounds presented the higher numbers of hydrogen bonds of selected chemicals supporting the drug-ability of these compounds. Among them, the established antiviral drug glycyrrhizic acid and the phytochemical theaflavin can be considered as possible drug compounds against target N protein of SARS-CoV-2 as they showed lower binding affinities. The findings of this study might lead to the development of a drug for the SARS-CoV-2 mediated disease and offer solution to treatment of SARS-CoV-2 infection.

Highlights

The outbreak of novel coronavirus infection has drastically affected the lives of the human population worldwide
The present study has focused on in silico discovery of potent leads from several antiviral drugs and compounds of plant origin against SARS-CoV-2 infection
Protein sequences of two distance homologues of SARSCoV-2 such as Ebola and H1N1 virus were included within the tree in order to establish sequential divergence pattern across species

Summary

Introduction

The outbreak of novel coronavirus infection has drastically affected the lives of the human population worldwide. This infection started as respiratory illness/pneumonia of unknown origin in Wuhan city of China at the end of the year 2019. The World Health Organization (WHO) declared it as a public health emergency of international concern as the disease spread to other regions of the world [1]. The official name of this infection was made as coronavirus disease 2019 (COVID-19) on 11 February 2020. The novel coronavirus is termed, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. SARS-CoV-2 infection mainly causes pneumonia, upper and lower respiratory tract infection with fever and

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