Regulation of epithelial sodium channel activity by SARS-CoV-1 and SARS-CoV-2 proteins

Severe acute respiratory syndrome (SARS) coronavirus (CoV) 2 (SARS-CoV-2), which causes the disease 2019, encodes several proteins whose roles are poorly understood. We tested their ability either to directly form plasma membrane ion channels or change functions of two mammalian channels, epithelial sodium channel (ENaC) and ?3?4 nicotinic acetylcholine receptor. In mRNA-injected Xenopus oocytes, none nine SARS-CoV-2 SARS-CoV-1 produced conductances, nor did co-injection combinations. Immunoblots for ORF8, spike (S), envelope (E) revealed that expressed at appropriate molecular weights. experiments on coexpression with ENaC, three SARS (SARS-CoV-1 E, S) markedly decrease ENaC currents. S protein decreases currents modestly. Coexpressing E but not receptors significantly reduces acetylcholine-induced inhibition does occur if SARS-CoV mRNAs injected 24 h after mRNAs, suggesting affect early step(s) in functional expression proteins. Consistent hypothesis protein-induced involves competition available protease, mutating furin cleavage site partially relieves Extending previous suggestions via kinase C (PKC) activation, PKC activation phorbol 12-myristate 13-acetate activity. Phorbol application reduced capacitance ?5%, presumably increased endocytosis, this is much smaller than proteins’ effects conductances. Also, incubating oocytes Gö-6976, a PKC? PKC? inhibitor, alter inhibition. conclude function human incompletely understood mechanisms. These interactions may play role 2019 pathophysiology.