Computational Drug Repurposing for the Development of Drugs Against Coronaviruses

Coronaviruses are single-stranded positive-sense RNA viruses possessing unique replication machinery, which consists of non-structural proteins (nsp1–16), structural proteins (S, E, M, N), and several accessory proteins. The non-structural proteins carry out activities critical for viral functions, and the structural proteins play a significant role in viral assembly and structure. The zoonotic nature of coronaviruses is responsible for the past epidemics and the current pandemic. The current global pandemic of COVID-19 caused by SARS-CoV-2 has caused infections worldwide and now crossed over a million fatalities. The high transmission rate of the virus has caused new cases emerging every day. While vaccines remain an ideal solution, it is also important to identify alternative potential small molecules and other inhibitors against molecular targets of SARS-CoV-2. The present chapter describes the current scenario of the world facing the COVID-19 pandemic and details the molecular machinery of the causative agent, i.e., SARS-CoV-2. It discusses the role of drug repurposing against SARS-CoV-2 and explains its methodology. It aims to provide an overview toward coronaviruses and the role and method of drug repurposing against crucial viral targets (here, 3CLpro as a case study) to create a report of current computational drug discovery approaches coherently.

Ligand-Based Approaches for the Development of Drugs Against SARS-CoV-2

The current COVID-19 pandemic caused by SARS-CoV-2 has now seen an unprecedented global trend of viral transmission leading to over a million fatalities worldwide. SARS-CoV-2 is a betacoronavirus which possesses a single-stranded positive-sense RNA genome that encodes various structural, non-structural, and accessory proteins. Due to the zoonotic nature of SARS-CoV-2 and current transmission trend, scientists must identify effective therapeutics against the virus. Ligand-based drug designing is a computational approach based on the principle that similar compounds exhibit similar activities;hence, it is employed to identify, screen, or design drug-like molecules based on the existing drug molecules. The present chapter provides an overview of SARS-CoV-2, COVID-19, viral drug targets and dives deeply into the computational approach of ligand-based drug designing (LBDD). The chapter aims to provide a detailed methodology of LBDD and the current research endeavors that have utilized the technique to identify, screen, or design potential drug molecules against SARS-CoV-2.