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

Breitinger U, Ali NK, Sticht H, Breitinger HG (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Frontiers in Microbiology Frontiers Media

Book Volume: 12

Article Number: 692423

DOI: 10.3389/fmicb.2021.692423

Abstract

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 is a small (∼8.4 kDa) channel-forming membrane protein whose sequence is highly conserved between SARS-CoV and SARS-CoV-2. As a viroporin, it is involved in various aspects of the virus life cycle including assembly, budding, envelope formation, virus release, and inflammasome activation. Here, SARS-CoV E protein was recombinantly expressed in HEK293 cells and channel activity and the effects of viroporin inhibitors studied using patch-clamp electrophysiology and a cell viability assay. We introduced a membrane-directing signal peptide to ensure transfer of recombinant E protein to the plasma membrane. E protein expression induced transmembrane currents that were blocked by various inhibitors. In an ion-reduced buffer system, currents were proton-dependent and blocked by viroporin inhibitors rimantadine and amantadine. I-V relationships of recombinant E protein were not pH-dependent in a classical buffer system with high extracellular Na+ and high intracellular K+. E-protein mediated currents were inhibited by amantadine and rimantadine, as well as 5-(N,N-hexamethylene)amiloride (HMA). We tested a total of 10 flavonoids, finding inhibitory activity of varying potency. Epigallocatechin and quercetin were most effective, with IC50 values of 1.5 ± 0.1 and 3.7 ± 0.2 nM, respectively, similar to the potency of rimantadine (IC50 = 1.7 ± 0.6 nM). Patch-clamp results were independently verified using a modified cell viability assay for viroporin inhibitors. These results contribute to the development of novel antiviral drugs that suppress virus activity and proliferation.

Authors with CRIS profile

Heinrich Sticht Professur für Bioinformatik

Involved external institutions

German University in Cairo (GUC) / الجامعة الألمانية بالقاهرة EG Egypt (EG)

How to cite

APA:

Breitinger, U., Ali, N.K., Sticht, H., & Breitinger, H.G. (2021). Inhibition of SARS CoV Envelope Protein by Flavonoids and Classical Viroporin Inhibitors. Frontiers in Microbiology, 12. https://dx.doi.org/10.3389/fmicb.2021.692423

MLA:

Breitinger, Ulrike, et al. "Inhibition of SARS CoV Envelope Protein by Flavonoids and Classical Viroporin Inhibitors." Frontiers in Microbiology 12 (2021).

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