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. Highlights 1. Entry of SARS‐CoV‐2 into a host cell depends on host protease TMPRSS2. 2. TMPRSS2 gene has localized expression throughout the human body but highly expressed in cells of the respiratory tract (primary target of SARS‐CoV‐2 in humans), gastrointestinal tract, kidneys and prostate. 3. Differences in expression of TMPRSS2 gene in the respiratory among different population groups can be a basis for discrepancy observed in COVID‐19 susceptibility and disease outcomes. 4. Drugs based on the inhibition or blockage of TMPRSS2 protease are undergoing clinical trials as a therapeutic option.
【저자키워드】 COVID‐19, coronavirus, SARS‐CoV‐2, viral entry, Differential gene expression, TMPRSS2 blockers, TMPRSS2 inhibitors, TMPRSS2, 【초록키워드】 Treatment, clinical trial, susceptibility, drug, outcome, COVID‐19, SARS‐CoV‐2, kidney, outcomes, Region, infections, humans, Entry mechanism, respiratory tract, pathogenicity, group, inhibitor, disease, expression, gastrointestinal tract, Prostate, host susceptibility, therapeutic option, host cell, ethnic group, viral spike protein, Factor, differential expression, enzyme, host protease TMPRSS2, SARS‐CoV‐2 infection, TMPRSS2 protease, enzyme activity, blocker, discrepancy, Affect, Cell, difference, highlight, affected, reported, investigated, determine, expressed, regulated, groups, implicated, 【제목키워드】 SARS‐CoV‐2, pathogenicity,