In silico design and pharmacokinetics investigation of some novel hepatitis C virus NS5B inhibitors: pharmacoinformatics approach

Abstract

Abstract Background Hepatitis C virus (HCV) is a contagious disease that damages the liver over time, eventually leading to cirrhosis and death. Chronic HCV infection is regarded as a serious health problem worldwide, impacting up to 3% of the populace and killing over 300,000 people annually. Quick reproduction driven by non-structural protein 5B (NS5B), which is a possible target spot for the development of anti-HCV vaccines, causes genomic diversity. Sofosbuvir, a new oral NS5B inhibitor, was recently licensed by the US Food and Drug Administration for the cure of HCV. Unfortunately, it has received a lot of attention due to its financial concerns and adverse effects. As a result, there is a pressing need to explore alternative HCV treatments that are both cost-effective and free of adverse effects. In this study, we used a Pharmacoinformatics-based strategy to identify and design bioactive molecules that are anti-HCV NS5B. The simulation outcomes are compared to Sofosbuvir simulation outcomes. Results Based on docking simulation, the proposed molecules have high-binding energies at the range of − 41.71 to − 39.90 kcal/mol against − 30.34 kcal/mol of Sofosbuvir. Furthermore, when compared to Sofosbuvir, which has a drug score of 0.31 (31% performance), the ADMET analysis of the lead compound demonstrates superior performance with a drug score of 0.88 (88% performance). Conclusions The findings revealed that alternative bioactive molecules vary substantially in docking rankings at a range of − 41.71 to − 39.90 kcal/mol against − 30.34 kcal/mol of Sofosbuvir, the FDA-approved NS5B enzyme inhibitor, and when compared to Sofosbuvir, which has a drug score of 0.31, the ADMET analysis of the chosen compound (1c) demonstrates superior performance with a drug score of 0.88.