TMPRSS2 As an Influential Human Gene for COVID-19

Abstract

: In December 2019, the new virus, COVID-19, emerged and led to a pandemic respiratory acute disease. Almost all countries have experienced different rates of morbidity and mortality. These differences can be attributed to factors such as a diagnostic test capacity for COVID-19 and the health system efficiency. Besides the differences between countries related to the COVID-19 management, different patients represent a diverse range of clinical symptoms, from outpatient to patients admitted to the intensive care unit (ICU) due to the severity of symptoms. To gain deeper insights into such disparities in the severity of COVID-19 clinical presentations, epidemiological studies have reported risk factors such as old age, male sex, underlying chronic diseases such as diabetes, inflammatory and cardiovascular diseases, which have a bearing on susceptibility to COVID-19. In addition to these risk factors, the molecular mechanism involved in the virus entry process has been under investigation. Apart from a well-known protein called ACE2 (angiotensin-converting enzyme 2), which plays the receptor role for COVID-19, another essential protein in this pathway is TMPRSS2 (transmembrane protease, serine 2). This protease has a crucial role in effective membrane integration between the virus and the target cell. This process can affect the severity of the infection and the mortality rate of the disease. Thus, it seems that understanding the role of TMPRSS2 in COVID-19 infection can help better management by designing TMPRSS2 inhibitors drugs. Given the variants of the TMPRSS2 gene, which are associated with the severity of symptoms, people exposed to severe forms of this disease can be identified before the deterioration of the disease to adopt appropriate therapeutic approaches. Therefore, this study focused on the different levels of the TMPRSS2 interactions with COVID-19 virus and disease severity.

TMPRSS2 polymorphism (rs12329760) and the severity of the COVID-19 in Iranian population

“…Most of these associated loci are involved in the molecular processes such as viral entry into the host cells, immune system and inflammatory responses [ 12 ]. The TMPRSS2 gene is one of the critical human genes in SARS-CoV-2 infection [ 13 ]. The SARS-CoV-2 interacts with some cellular proteins to enter the cell and make a successful infection: the spike glycoprotein on the surface of the virus is first cleaved by a set of cellular proteases, including the TMPRSS2 enzyme, and is converted into S1 and S2 subunits.…”