ORF3a has longer Thiol_cytolys_C motifs. It can all be combined to form dimmers and tetramers. Multimers can be used to construction ion channels. As a result, ORF3a possess cytolysin activity that is activated by thiols. We discovered that ORF3a's "YFLQSINFVRIIMRLWLCWKCRSKNPLLYDANYFLCWHTNCYDYCIPYN" (residues 113-161) contains the B30.2/SPRY domain structure (IPR001870). The SPRY domain is present in the calcium release channel of ryanodine receptors in mammals(101). The protein's SPRY domain is homologous to their respective Thiol_cytolys_C domains. It indicates that the thiol activated cytolysin-built pores in ORF3a acts as calcium release channels. Calcium is required for blood clotting. ORF3a generates pore via Thiol-cytolys hemolysin. The clotting factor calcium ions are released by the SPRY domain regulates the hemolysis of red blood cells. Thiol-activated cytolysins are cholesterol-dependent cytolysins. It is oxygen-sensitive, and its activity is reduced when the oxygen supply is constant or high. So the hemolysin domain of ORF3a is active only in the presence of hypoxia.