Spiking dependence of SARS‐CoV‐2 pathogenicity on TMPRSS2

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.

Aggregation of high‐frequency RBD mutations of SARS‐CoV‐2 with three VOCs did not cause significant antigenic drift

“…First, we focused on exploring changes in the infectivity of possible variants in several primate cells (Huh‐7, LLC‐MK2, and Vero) susceptible to infection with SARS‐CoV‐2 and four 293T‐hACE2/Furin/TMPRSS2/Cathepsin L stably transfected cell lines containing SARS‐CoV‐2 infection‐associated enzymes. 28 , 29 , 30 , 31 Compared with the corresponding three VOCs, among the possible Alpha variants, Alpha+A520S showed a significant increase in infectivity of more than fourfold in LLC‐MK2 and Vero cells. Alpha+S494P and Alpha+V367F also enhanced infectivity within fourfold (Figure 2A ).…”

Coronavirus Infection and Cholesterol Metabolism

“…Therefore, cholesterol depletion from cellular membranes using e.g., methyl-β-cyclodextrin (MβCD) eliminates cholesterol in lipid rafts and significantly reduces clathrin-dependent endocytosis to significantly eliminate IBV, TGEV, and SARS-CoV infectivity ( Figure 1A ) ( 117 , 119 , 127 ). In addition, SARS-CoV-2 pathogenicity was significantly dependent on TMPRSS2 ( 128 ). Contributions of human ACE2 and TMPRSS2 in determining host-pathogen interaction of COVID-19 ( 129 ).…”

A Role of Variance in Interferon Genes to Disease Severity in COVID-19 Patients

“…As the diseases associated with the use of these medications are commonly comorbid with COVID-19 (Lopera Maya et al, 2020), these findings may eventually prove their relevance to COVID-19 severity. Drugs based on the inhibition or blockage of TMPRSS2 protease are undergoing clinical trials as a therapeutic option for COVID-19 treatment (Abbasi et al, 2021). Thus, there remains continued interest in studying the ACE2 and TMPRSS2 genes as determinants of susceptibility to SARS-CoV-2.…”