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Review
. 2021 Jul;93(7):4205-4218.
doi: 10.1002/jmv.26911. Epub 2021 Mar 18.

Spiking dependence of SARS-CoV-2 pathogenicity on TMPRSS2

Asim Z Abbasi  1 , Dania A Kiyani  1 , Syeda M Hamid  1 , Muhammad Saalim  1   2 , Ammad Fahim  3 , Nasir Jalal  1   4
Affiliations
Review

Spiking dependence of SARS-CoV-2 pathogenicity on TMPRSS2

Asim Z Abbasi et al. J Med Virol. 2021 Jul.

Abstract

Epidemiological data shows a discrepancy in COVID-19 susceptibility and outcomes with some regions being more heavily affected than others. However, the factors that determine host susceptibility and pathogenicity remain elusive. An increasing number of publications highlight the role of Transmembrane Serine Protease 2 (TMPRSS2) in the susceptibility of the host cell to SARS-CoV-2. Cleavage of viral spike protein via the host cell's TMPRSS2 enzyme activity mediates viral entry into the host cell. The enzyme synthesis is regulated by the TMPRSS2 gene, which has also been implicated in the entry mechanisms of previously reported Coronavirus infections. In this review, we have investigated the pathogenicity of SARS-CoV-2 and disease susceptibility dependence on the TMPRSS2 gene as expressed in various population groups. We further discuss how the differential expression of this gene in various ethnic groups can affect the SARS-CoV-2 infection and Coronavirus disease (COVID)-19 outcomes. Moreover, promising new TMPRSS2 protease blockers and inhibitors are discussed for COVID-19 treatment.

Keywords: COVID-19; SARS-CoV-2; TMPRSS2; TMPRSS2 blockers; TMPRSS2 inhibitors; coronavirus; differential gene expression; viral entry.

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Conflict of interest statement

The authors declare that there are no conflict of interests.

Figures

Figure 1
Figure 1
Functional domains of TMPRSS2 protein and their location in the protein sequence. TMPRSS2 contains the noncatalytic chain(1–255) and catalytic chain (256–492). The catalytic chain contains HIS 296, ASP 345, and SER 441 residues, which function as the binding and catalytic sites. ASP (D), HIS (H), LDL receptor class A (LDLRA) domain, scavenger receptor cysteine‐rich (SRCR) domain, SER (S), serine protease (SP) domain, and transmembrane (TM) domain
Figure 2
Figure 2
Role of TMPRSS2 protease in SARS‐CoV‐2 in infection. After binding of the SARS‐CoV‐2 S‐protein with the ACE2 receptor, the S‐protein is primed by TMPRSS2 protease that results in the viral entry. Plus (+) sign indicates all the factors that increase TMPRSS2 protease expression and SARS‐CoV‐2 priming. Inhibitor (‐‐‐) sign indicates therapeutic targets that can have inhibitory action against TMPRSS2 protease
See this image and copyright information in PMC

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