Assessing multi-target antiviral and antioxidant activities of natural compounds against SARS-CoV-2: an integrated in vitro and in silico study

Abstract There is an urgent need for preventive and therapeutic drugs to effectively treat and prevent viral diseases from resurfacing as they emerge during the COVID-19 pandemic. This study aims to assess the antiviral effects of four natural compounds commonly used in traditional medicine to treat SARS-CoV-2 infection. A cytotoxicity, dose-dependent, and plaque reduction assay was performed on Vero CCL-81 cells to figure out their effects on the cells. Quantification of cytokines was assessed. In silico analysis for the selected compound was also evaluated. Results revealed that the compounds could disrupt the viral replication cycle through direct inhibition of the virus or immune system stimulation. The cytotoxicity assay results revealed that the compounds were well tolerated by the cells, indicating that the compounds were not toxic to the cells. This study evaluated the antioxidant capacities of propolis, curcumin, quercetin, and ginseng using ABTS, FRAP, and CUPRAC assays, revealing that propolis exhibited the highest antioxidant activity of ABTS with 1250.40 ± 17.10 μmol Trolox eq/g, with FRAP values reaching 1200.55 ± 15.90 μmol Fe2⁺ eq/g and CUPRAC values of 1150.80 ± 14.20 μmol Trolox eq/g at 1000 µg/mL, highlighting its potential as a potent natural antioxidant. The results of the plaque reduction assay revealed that the compounds could reduce the size and number of plaques, indicating that the compounds could inhibit the virus replication cycle. Subsequently, using molecular docking to analyze the effect of propolis, curcumin, quercetin, and ginseng as inhibitors, it was unveiled that the four compounds are likely to have the potential to inhibit the protease activity, spike protein S1, and RNA polymerase of SARS-CoV-2 and the virus titer was reduced by 100% after post-infection using propolis as an inhibitor control. Graphical Abstract