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.