Discovery of biogenic-based compound as potential heat-shock protein 90 inhibitor through fragment-based drug design

Abstract

Ebola virus (EBOV) is a negative-sense RNA virus that belongs to Filoviridae family which recognized as one of the deadliest virus that can cause severe haemorrhagic fever. Recent studies have shown that heat-shock protein 90 (Hsp90), an essential molecular chaperone, plays an imperative role in the replication of EBOV. In the present study, about 112,113 biogenic compounds from ZINC15 database were screened through computational study through Rule of Three, druglikeness, and toxicity screening, followed by molecular docking simulation to determine the potential biogenic-based compound as lead compounds. These compounds were later linked by each other to generate a novel compound for inhibiting Hsp90 protein. Throughout this study, about 742 fragments were obtained through the first screening process, while the first docking simulation produced 452 lead fragments. After the linking processes were conducted, about 81 compounds were produced through the second docking simulation. Furthermore, the docking simulation also revealed that HAI_77 gave the best ligand interaction and had the lowest Gibbs free binding energy at -14.157 kcal/mol. Thus, HAI_77 ligand can be proposed as novel drug candidates for the EBOV therapeutics targeting Hsp90 ligand.