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TMPRSS2: An Equally Important Protease as ACE2 in the Pathogenicity of SARS-CoV-2 Infection

      The current pandemic (coronavirus disease 2019 [COVID-19]) has caused more than 135 million infections and more than 3 million deaths worldwide. Angiotensin-converting enzyme 2 (ACE2) plays a substantial role for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to gain entry into the host cells and has been recognized since the beginning of the pandemic with more than 6000 publications (PubMed as of April 9, 2021), whereas the role of transmembrane protease, serine 2 (TMPRSS2) is of equal importance though underrecognized with only one-fifth of the publications (1939). In the pathogenicity of SARS-CoV-2, in addition to ACE2 and TMPRSS2 other host factors such as FURIN and neuropilin 1 are important. However, in this perspective we discuss the critical role of TMPRSS2
      • Hoffmann M.
      • Kleine-Weber H.
      • Schroeder S.
      • et al.
      SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor.
      ,
      • Hou Y.
      • Zhao J.
      • Martin W.
      • et al.
      New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis.
      and highlight that both ACE2 and TMPRSS2 are equally important. The coexpression
      • Sungnak W.
      • Huang N.
      • Becavin C.
      • et al.
      HCA Lung Biological Network. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes.
      of both ACE2 and TMPRSS2 in the host target cells is important for the SARS-CoV-2 entry into the target cells. It is important to consider strategies to target TMPRSS2 to control the SARS-CoV-2 infection and the pandemic
      • Baughn L.B.
      • Sharma N.
      • Elhaik E.
      • Sekulic A.
      • Bryce A.H.
      • Fonseca R.
      Targeting TMPRSS2 in SARS-CoV-2 infection.
      until a safe and effective vaccine against SARS-CoV-2 and its variants becomes available.
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