Exploring Phytochemicals from Nigella sativa as novel NS2B/NS3 protease inhibitors of dengue virus: A Pharmacoinformatic Study.

Background objectives: Dengue virus, a mosquito-borne flavivirus, is a serious worldwide health risk that can be fatal. Its replication is dependent on the NS2B/NS3 protease. Given the critical need for effective antivirals and the documented medicinal properties of Nigella sativa bioactive compounds, this study used molecular docking and ADMET analysis to assess the potential of N. sativa bioactive compounds as NS2B/NS3 protease inhibitors.

Methods: A total of 151 bioactive compounds from N. sativa were retrieved from the PubChem database. Molecular docking analyses were carried out using AutoDock Vina in conjunction with PyRx (v. 0.8) virtual screening tools. Physiochemical and ADMET properties of the top four compounds were evaluated using SwissADME and Deep-PK tools.

Results: The screening resulted 19 compounds with higher binding affinity values than the control compound Lopinavir. This study focused on the top four compounds (PubChem IDs: 11277543, 118717506, 101257318, and 102575929) that were found to form multiple hydrogen bonds and hydrophobic interactions with the NS2B/NS3 protease active site. Importantly, these compounds interacted with the catalytic triad of His51, Asp75, and Ser135 residues of NS2B/NS3 protease. Furthermore, these compounds had favourable druglikeness, pharmacokinetic, and toxicity profiles.

Interpretation conclusion: The compounds (PubChem IDs: 11277543, 118717506, 101257318, and 102575929) can be used as potential NS2B/NS3 protease inhibitors for further experimental validation and development in dengue management.