SARS-CoV-2 Can Gain Cell Entry Via Host Proteases TMPRSS2 or Furin; While TMPRSS Is Present Chiefly in the Lungs, Furin Has a Much Wider Tissue Distribution and May Thus Be Responsible for COVID-19’s Broader Than Usual Pathogenicity; Dual Inhibitor Sought

How might the novel coronavirus SARS-CoV-2 be prevented from entering a host cell in an effort to thwart infection? A team of biomedical scientists has made a discovery that points to a solution. The scientists, led by Maurizio Pellecchia, PhD, Professor of Biomedical Sciences in the School of Medicine at the University of California, Riverside (UC-Riversidie), in an article published online on May 22, 2020 in Molecules report that two proteases (enzymes that break down proteins) located on the surface of host cells and responsible for processing viral entry could be inhibited. Such protease inhibition would prevent SARS-CoV-2, the coronavirus responsible for COVID-19, from invading the host cell. The research is featured as the cover story of the May 2020 issue of the journal (Volume 25, Issue 10). The open-access article is titled “Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming.” The outer surface of coronaviruses contains a critical protein called spike glycoprotein, or S-glycoprotein. Responsible for giving the coronavirus its typical crown shape, the S-glycoprotein is essential for the entry of viral particles into host cells. Host cell proteases, however, must first process or cut this viral surface protein to allow the virus to enter the cells. Dr. Pellecchia's lab and others have recognized that in addition to a previously identified protease called TMPRSS2 (transmembrane serine protease 2), the new SARS-CoV-2 coronavirus can also be processed by an additional human protease, called furin (image), for viral entry. "The use of the host protease furin for processing is a common mechanism of cell entry by both viral fusion proteins and certain bacterial toxins," said Dr. Pellecchia, who led the research team. "SARS-CoV-2 uses this mechanism also.
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