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A compound against SARS shows promise against the COVID-19 virus

"Striking similarities" between the two viruses make them vulnerable to the same compounds.

Alexandru Micu
March 9, 2020 @ 7:45 pm

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Commonalities between the coronavirus responsible for the current outbreak and the SARS virus could point the way towards a treatment option, a new paper reports.

Graphical abstract of the study.
Image credits Hoffman et al., (2020), Cell.

SARS (severe acute respiratory syndrome) was capturing headlines and causing panic around the world back in 2003. The virus responsible for SARS — SARS-CoV — is a coronavirus related to the current SARS-CoV-2 virus that is at the root of the current global outbreak. SARS eventually resulted in more than 8,000 cases and 800 deaths, but was contained through a combination of “surveillance, prompt isolation of patients, strict enforcement of quarantine of all contacts, and in some areas top-down enforcement of community quarantine,” according to a study (A. Wilder-Smith, J. Chiew, J. Lee, 2020) published last week in The Lancet.

“By interrupting all human-to-human transmission, SARS was effectively eradicated. By contrast, by Feb 28, 2020, within a matter of 2 months since the beginning of the outbreak of coronavirus disease 2019 (COVID-19), more than 82,000 confirmed cases of COVID-19 have been reported with more than 2,800 deaths,” the study adds.

“Although there are striking similarities between SARS and COVID-19, the differences in the virus characteristics will ultimately determine whether the same measures for SARS will also be successful for COVID-19.”

The “striking similarities” the authors note here may, however, point us to a viable treatment option for the COVID-19 disease caused by the SARS-CoV-2 virus.

Birds of a feather get shot together

Published in the journal Cell, the new study explains that structural similarities between the two viruses allow for a substance already approved for clinical use against SARS to engage the COVID-19 virus and that natural antibodies against SARS “may offer some protection” against the current outbreak.

“A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option,” the authors explain. “Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between [the two viruses] and identify a potential target for antiviral intervention.”

TMPRSS2, or transmembrane protease serine 2, is an enzyme (protein) in the serine protease family that “is associated with […] processes such as digestion, tissue remodeling, blood coagulation, fertility, inflammatory responses, tumor cell invasion, and apoptosis [cellular death],” according to Sciencedirect. According to the findings, the COVID-19 virus relies on this enzyme to reproduce (by multiplying its genes inside infected cells). The authors further report that the virus enters human cells by using ACE2 (angiotensin converting enzyme 2) receptors on its viral casing.

This process is the same one used by the SARS virus. A more exciting finding was that a TMPRSS2-inhibiting compound already approved for use against SARS successfully prevented the COVID-19 virus from infecting human cells. In addition, the team found that serum derived from the blood of former SARS patients — which contains natural antibodies against it — is “moderately effective” in protecting individuals from infection with the COVID-19 virus.

“Although confirmation with infectious virus is pending, our results indicate that neutralizing antibody responses raised against SARS-S could offer some protection against SARS-CoV-2 infection, which may have implications for outbreak control,” they explain.

While the findings are definitely encouraging, there are still unknowns left to sort out. For example, the higher infection rates seen in COVID-19 compared to SARS could mean that the new coronavirus is better able to bind to the ACE2 receptors in cells in the upper respiratory tract. More research is needed, and fast, to elucidate these issues, the team explains, but they are hopeful that their findings lay the groundwork for such efforts in the future.

The paper “SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor” has been published in the journal Cell.

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