In Silico Study of Alkaloids: Neferine and Berbamine Potentially Inhibit the SARS-CoV-2 RNA-Dependent RNA Polymerase

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, has been a global concern. While there have been some vaccines and drugs, the rapid emergence of variants due to mutations has threatened public health. As the de novo drug development process is expensive and time-consuming, repurposing existing antiviral drugs against SARS-CoV-2 is an alternative and promising approach to mitigate the current situation. Several studies have indicated that some natural products exhibit inhibitory activities against SARS-CoV-2. This study is aimed at analyzing the potential of natural alkaloids, using various computational tools, as drug candidates against SARS-CoV-2. The molecular docking analysis predicted that naturally occurring alkaloids can bind with RNA-dependent RNA-polymerase (RdRP). The QSAR analysis was conducted by using the way2drug/PASS online web resource, and the pharmacokinetics and toxicity properties of these alkaloids were predicted using pkCSM, SwissADME, and ProTox-II webserver. Among the different alkaloids studied, neferine and berbamine were repurposed as potential drug candidates based on their binding affinity and interactions with RdRP. Further, molecular dynamics simulation of 90 ns revealed the conformational stability of the neferine-RdRP complex.