Inhibition of SARS CoV Envelope Protein by Flavonoids and Classical Viroporin Inhibitors

Severe acute respiratory syndrome coronavirus (SARS-CoV), an enveloped single-stranded positive-sense RNA virus, is a member of the genus Betacoronavirus , family Coronaviridae. The SARS-CoV envelope protein E small (?8.4 kDa) channel-forming membrane whose sequence highly conserved between and SARS-CoV-2. As viroporin, it involved in various aspects virus life cycle including assembly, budding, formation, release, inflammasome activation. Here, was recombinantly expressed HEK293 cells channel activity effects viroporin inhibitors studied using patch-clamp electrophysiology cell viability assay. We introduced membrane-directing signal peptide to ensure transfer recombinant plasma membrane. expression induced transmembrane currents that were blocked by inhibitors. In ion-reduced buffer system, proton-dependent rimantadine amantadine. I-V relationships not pH-dependent classical system with high extracellular Na + intracellular K . E-protein mediated inhibited amantadine rimantadine, as well 5-(N,N-hexamethylene)amiloride (HMA). tested total 10 flavonoids, finding inhibitory varying potency. Epigallocatechin quercetin most effective, IC 50 values 1.5 ± 0.1 3.7 0.2 nM, respectively, similar potency (IC = 1.7 0.6 nM). Patch-clamp results independently verified modified assay for These contribute development novel antiviral drugs suppress proliferation.