1.A.127. The SARS-CoV-2 ORF7b Viroporin (ORF7b Viroporin) Family
The dire need for COVID-19 treatments has inspired strategies of repurposing approved drugs. Amantadine has been suggested as a candidate, and cellular as well as clinical studies have indicated beneficial effects of this drug. Toft-Bertelsen et al. 2021 demonstrated that amantadine and hexamethylene-amiloride (HMA), but not rimantadine, block the ion channel activity of Protein E from SARS-CoV-2, a conserved viroporin among coronaviruses. They bind to Protein E as evaluated by solution NMR and molecular dynamics simulations. They identified two novel viroporins of SARS-CoV-2; ORF7b and ORF10, by showing ion channel activity in an X. laevis oocyte expression system. Amantadine also blocks the ion channel activity of ORF10. A screen of known viroporin inhibitors on Protein E, ORF7b, ORF10 and Protein 3a from SARS-CoV-2 revealed inhibition of Protein E and ORF7b by emodin and xanthene, the latter also blocking Protein 3a. This illustrates a general potential of well-known ion channel blockers against SARS-CoV-2 and specifically a dual molecular basis for the promising effects of amantadine in COVID-19 treatment. Amantadine could be a novel, cheap, readily available and effective way to treat COVID-19 (Toft-Bertelsen et al. 2021). The protein members of this family are all small (40 - 60 aas in length) with a single TMS. They do not show appreciable sequence similarity with other protein s in TCDB as of 1/2022.