Orf3a of 275 aas and 3 central TMSs. Orf3a forms homodimers and homotetramers and is a non-selective catioin channel that is blocked by polycation channel inhibitors (Kern et al. 2021). They carry a PDZ-binding domain, lending them the versatility to interact with more than 400 target proteins in infected host cells. Structural considerations have been discussed (Barrantes 2021). Naturally occurring mutations in ORF3a are common and have been analyzed, and 28 fully concerved residues in 70,000 sequences that probably have structural or functional roles were also identified (Bianchi et al. 2020). Viroporin 3a exhibits allosteric properties (Tee et al. 2021). It has been implicated in apoptosis and inhibition of autophagy. The structure of the dimer has been determined at 2.1 Å resolution by cryoEM (Kern et al. 2021). Pentamidine is a channel blocker of Orf3a (Zhang et al. 2022).