Computational exploration of Andrographis paniculata herb compounds as potential antiviral agents targeting NSP3 (6W02) and NSP5 (7AR6) of SARS-COV-2

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, requires an urgent search for effective antiviral agents. NSP3 and NSP5, play critical roles in the replication and transcription. This study aimed to screening the physicochemical properties, toxicity, and antiviral potential of herbal compounds from Andrographis paniculata against NSP3 (6W02) and NSP5 (7AR6) of SARS-CoV-2. The herb compounds were obtained from the KNApSAcK Family and PubChem databases. Their interactions with Remdesivir, an FDA-approved antiviral for SARS-CoV-2, NSP3 and NSP5 were analyzed using molecular docking through Molegro Virtual Docker 6.0. There are 27 compounds out of a total of 41 herb compounds that meet the Veber Rule and have predicted good physicochemical properties. Moreover, 15 herb compounds predicted to be non-toxic based on GHS, not-mutagenic, not-carcinogenic, and not-allergenic to the skin. The screening results using PASS Online showed 5 compounds highly potential to be candidates for SARS-CoV-2 antivirals, namely: 12S-Hydroxyandrographolide, 14-Deoxy-11,12-didehydroandrographolide, Andrographolide, Andropanolide, and Isoandrographolide. Based on molecular docking results, it was found both Remdesivir and the herb compounds still required more energy than the native ligand on the 6W02 target protein. In contrast, for the 7AR6 target protein, both Remdesivir and herb compounds required less energy than the native ligand. In conclusion, A. paniculata herb compounds showed inhibitory activity on 6W02 and 7AR6 receptors, suggesting their potential as herbal treatments for SARS-CoV-2 antivirals by targeting the NSP3 and NSP5 proteins. Further validation through in vitro and in vivo studies is needed.