1.A.49 The Human Coronavirus ns12.9 Viroporin (ns12.9) Family
The ns12.9 protein is a transmembrane protein that forms ion channels in both Xenopus oocytes and yeast through homo-oligomerization. HCoV-OC43-Δns12.9 was 10-fold less virulent than the wild type virus. Exogenous ns12.9 and heterologous viroporins with ion channel activity could compensate for the loss of ns12.9, indicating that the ion channel activity of ns12.9 is necessary for the production of infectious virions. Systematic dissection of single-cycle replication revealed that the ns12.9 protein had no measurable effect on virus entry, subgenomic messenger RNA (sgmRNA) synthesis and protein expression. The deletion mutant was less efficient in virion morphogenesis than the wild type and reduced viral replication, inflammatory response and virulence (Zhang et al. 2015). Thus, ns12.9 is a viroporin involved in virion morphogenesis and the pathogenesis. All members of this family have C-terminal putative amphipathic helices that could be transmembrane, but no strongly hydrophobic TMSs. Drugs and drug targets that are relevant to Covid-19 treatment have been reviewed (Ayele et al. 2021).