3.1.1 Modification of host cell serine protease
Despite the possibility of surface alteration of RNA viruses, blocking the viral receptor protein on the host cell surface, thereby inhibiting the virus entry, can be a proper option in the drug discovery process. Transmembrane Serine Protease 2 (TMPRSS2) that mediate the entry by distinct mechanisms. One is cleavage and activation of the spike glycoproteins of coronaviruses (like HCoV-229E and HCoV-EMC) which facilitates the virus-cell membrane entry. Conformational flexibility of S protein which is needed for fusion is facilitated by proteolytic cleavages (Bosch et al., 2003) which is catalyzed by TMPRSS2 as the most relevant cellular proteases in this process. Another mechanism is the proteolytic cleavage of angiotensin-converting enzyme 2 (ACE2), which might activate the coronavirus spike glycoprotein for cathepsin L-independent host cell entry.