TCDB is operated by the Saier Lab Bioinformatics Group

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 proteins in TCDB as of 1/2022. Amantadine has potential for the treatment of COVID-19 because it inhibits viroporin ion channels encoded by SARS-CoV-2(Toft-Bertelsen et al. 2021). SARS-CoV-2 accessory protein 7b forms homotetramers in detergent (Surya et al. 2022).

References associated with 1.A.127 family:

Surya, W., M. Queralt-Martin, Y. Mu, V.M. Aguilella, and J. Torres. (2022). SARS-CoV-2 accessory protein 7b forms homotetramers in detergent. Virol J 19: 193. 36414943
Toft-Bertelsen, T.L., M.G. Jeppesen, E. Tzortzini, K. Xue, K. Giller, S. Becker, A. Mujezinovic, B.H. Bentzen, L. B Andreas, A. Kolocouris, T.N. Kledal, and M.M. Rosenkilde. (2021). Amantadine has potential for the treatment of COVID-19 because it inhibits known and novel ion channels encoded by SARS-CoV-2. Commun Biol 4: 1347. 34853399