Loading...
The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which shares high amino-acid sequence homology with the SARS coronavirus that emerged in 2002. The surface unit (S1) of the spike (S) protein of SARS engages the angiotensin-converting enzyme 2 (ACE2) as the entry receptor and then uses the host serine protease TMPRSS2 for S priming, allowing fusion of viral and cellular membranes and viral entry into the cell. Researchers have now examined how the S protein from SARS-CoV-2 facilitates viral entry into target host cells and compare the process to that used by SARS.
They found that:
The S proteins of SARS and SARS-2 mediate viral entry into a similar spectrum of cell lines.
Like SARS, SARS-CoV-2 employs the same host-cell ACE2 as the receptor for cell entry.
The host cell serine protease TMPRSS2 primes the S protein of SARS-CoV-2 for entry.
The serine protease inhibitor camostat mesylate, available in Japan to treat chronic pancreatitis and reflux esophagitis, inhibits TMPRSS2 and partially blocks SARS-CoV-2 infection of lung epithelial cells.
Antibodies against S1 from convalescent sera of SARS patients inhibited SARS-CoV-2 from infecting cultured cells.
Hoffmann M et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020 Mar 5; [e-pub]. (https://doi.org/10.1016/j.cell.2020.02.052)
Comment
Although offering a promising therapeutic and vaccine target against SARS-CoV-2, these new findings remind us that the viral pathogenesis of COVID-19 focuses on blood-pressure homeostasis mediated by the renin-angiotensin system (Future Virology 2010; 5:145). High risk for severe COVID-19 disease has been assumed to be driven largely by waning innate immunity that comes with advanced age, but younger patients with cardiovascular disease or hypertension may have unappreciated risk (NEJM JW Infect Dis Mar 2020 and Lancet 2020; 395:565). Clinical studies are needed to help translate how the interaction of SARS-CoV-2 with the renin-angiotensin system can be harnessed therapeutically (Lancet Respir Med 2020 Mar 11; [e-pub] and Drug Dev Res 2020; Mar 4 [e-pub]).