SARS-COV-2 Ingress - Triggering COVID-19 Infection

An important keynote that should be kept in mind is that to curb the spreading of the SARS-CoV-2 virus, one should understand how it enters host cells. This review provides deep insights into mechanistic intervention approaches of 2019- nCoV that target its host cell entry mechanisms. Majorly, there are three entryways for 2019-nCoV to target and infect the host cell, which is highly expressed with ACE2. The ‘S’- priming of TMPRSS2 associated cleavage is the primary entryway for a virus to access the targeted host cell via mediating the fusion process. The second way for virus entry is through the endocytosis phenomenon. The third way for virus entry is S pre-priming or S pre-cleaving of furin mediated fusion. Recent studies have proved that S1/S2' is a proteolytic cleavage site responsible for mediating viral entry. Hence, several protease inhibitors could be the potential targets to block proteolytic cleavage of the spike protein. This review describes the different entryways of 2019-nCoV and the impactful role of TMPRSS2 and furin host enzymes for a virus to get access into the targeted host cell; pre-fusion and post-fusion conformational states of 2019-nCoV spike protein; the role of viral suppressors of RNA in host immune evasion and the role of SPs, NSPs, and Orfs of 2019-nCoV in host immune evasion (host IFN response). Mutations of 2019-nCoVand its variants are reviewed in this article. 

Keywords: Furin, hACE2, Immune evasion, Omicron, Post-fusion, Pre-fusion, Priming, Spike protein, TMPRSS2.