Computational Modeling of RdRp Inhibitors for the Development of Drugs against Novel Coronavirus (nCoV)

ABSTRACT

Corona virus disease 2019, known as COVID-19, is a type of viral infection, which may cause acute respiratory infection and severe pneumonia, for which there is no specific therapeutic treatment. The available drugs are used only for symptomatic relief. Among all the targets, RNA-dependent RNA polymerase (RdRp) has been proved as an optimistic drug target against severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) to manage its replication process. There are number of molecules which have been approved by the FDA as RdRp inhibitors such as ribavirin, remdesivir, sofosbuvir, etc. The reported inhibitors for RdRp enzyme is being used by the various researchers for repurposing of drugs against SARS-Cov-2 RdRp enzyme by implementing different computational methodologies. Molecular modeling and cheminformatics approaches have been used for the design and identification of novel molecules having medicinal applications in various areas. The preliminary studies in computational drug discovery (CDD) and in silico approaches are important parts of the modern drug discovery practices, and they are frequently applied in the identification of new drugs or for the prediction of biological activity of chemical series. Now, in the ongoing corona pandemic, in silico modeling is being proved very helpful for easy identification of novel inhibitors. The current chapter presents recent reports on the application of computational modeling approaches for the design and identification of ligands against RdRp associated with SARS-CoV-2. Here, we will illustrate recently published computational studies for the identification or development of novel RdRp inhibitors applying different computational approaches, encompassing homology modeling, molecular docking, virtual screening, and molecular dynamics simulations. The chapter will also provide the reader an overall idea about a successful computational drug discovery research in this particular area of applications.