Inhibitory Activity of Natural Flavonoids against N439K Variant of SARS-CoV-2 Spike Protein: an In Silico Analysis

Abstract

Angiotensin-converting enzyme 2 (ACE2) is a functional receptor of the spike protein SARS-CoV-2 that plays an important role in the pathogenesis of COVID-19, especially in providing a passage for the virus to enter human cells. Flavonoids have high bioactivity beneficial for health, such as anti-inflammatory, anticancer, antioxidant, anti-lipogenic, metal-chelating, antimicrobial, and antiviral properties. We predict that flavonoids can be used as inhibitors for spike protein and ACE2 interaction. This study aims to compare the potential of flavonoid compounds in herbal medicine as an inhibitor for the spike protein and ACE2 receptors interaction to prevent COVID-19 transmission. Curcumin, 6-gingerol, luteolin, brazilin and kaempferol were used as ligands to dock with wild-type S protein and N439K variant S protein. Drug likeness properties were also evaluated using SwissADME. Molecular docking analysis of five active compounds of flavonoid to wild-type S protein and ACE2 complex shows kaempferol to have the lowest binding energy, meanwhile for mutant S protein and ACE2 complex, 6-gingerol has the lowest binding energy. Both compounds also form hydrogen bonds at the most active binding site. Kampferol showed the best inhibitory activity for wild-type variant. In contrast, 6-gingerol might have the best potential to interfere S protein-ACE2 interaction for the N439K variant S protein.