In silico analysis of bioactive compounds of Nigella sativa as potential inhibitors of NS5B RdRp protein involved in the pathogenesis of hepatitis C virus.

Abstract

The Hepatitis C virus (HCV) is a small, enveloped virus characterized by a positive-sense single-stranded RNA belonging to the Flaviviridae family. It causes hepatitis C, which leads to liver inflammation. It manifests as both acute and chronic hepatitis, ranging from mild illness to life-threatening conditions, such as liver fibrosis, cirrhosis, and hepatocellular carcinoma. The NS5B RNA-dependent RNA polymerase (RdRp) protein plays a vital role in the replication of the hepatitis C virus as the main RNA-synthesizing enzyme. It is crucial for forming new viral RNA, making it an ideal target for antiviral drugs. Inhibiting NS5B can inhibit virus replication, potentially preventing severe liver diseases, including cancer. Scientists have mapped the structure of the NS5B RdRp, revealing how different inhibitors interact with it, guiding the creation of targeted drugs. Nigella sativa, known for diverse bioactive compounds, is now being explored for its potential to combat viruses. Our research aims to determine whether compounds extracted from Nigella sativa can inhibit the NS5B RdRp enzyme of HCV. Through advanced computational analysis and molecular docking, Nigella sativa's phytoconstituents were scrutinized for their ability to bind and potentially inhibit NS5B RdRp. Amentoflavone, Rutin, and Catechin were selected based on their pharmacokinetic and enzyme-binding properties, which prompted further examination. Thorough molecular dynamics simulations affirmed the formation of stable complexes between these molecules and NS5B RdRp and provided valuable information about their influence on the enzyme's structural stability. The findings suggest these compounds have potent inhibitory actions, highlighting them as potential natural medicinal options against hepatitis C.