KroganLab Camostat mesylate binds to a protein on human cells called TMPRSS2. And SARS-CoV-2 needs this protein to efficiently enter human cells: The spike protein on top of the virus attaches to the ACE2 receptor on human cells. And then TMPRSS2 needs to make a cut in the spike.
“We knew from our previous work that camostat mesylate was active against other coronaviruses, including SARS-CoV. Therefore, we tested whether it is also active against SARS-CoV-2,” said Stefan Pöhlmann, PhD, Professor in the same institute in Göttingen. “Our study shows that camostat mesylate blocks infection of cells with SARS-CoV-2-like particles and with authentic, patient-derived SARS-CoV-2. Moreover, camostat mesylate inhibited infection of important target cells – human lung epithelial cells,” he added.
Here, we demonstrate that 2019-nCoV-S uses the SARS-coronavirus receptor, ACE2, for entry and the cellular protease TMPRSS2 for 2019-nCoV-S priming. A TMPRSS2 inhibitor blocked entry and might constitute a treatment option. Finally, we show that the serum form a convalescent SARS patient neutralized 2019-nCoV-S-driven entry. Our results reveal important commonalities between 2019-nCoV and SARS-coronavirus infection, which might translate into similar transmissibility and disease pathogenesis. Moreover, they identify a target for antiviral intervention.
The present study suggests that 2019-nCoV spread might also depend on TMPRSS2 activity and it is noteworthy that the serine protease inhibitor camostat mesylate blocks TMPRSS2 activity (24, 26) and has been approved in Japan for human use, although for an unrelated indication. This compound or related ones should be considered for treatment of 2019-nCoV infected patients.
The researchers claim that this new virus strain, named COVID-19, bears a striking 72.8% resemblance in structure to the SARS strain, and so the researchers tested the way in which COVID-19 attaches itself to the ACE2 enzyme, which is part of almost every cell in the human body and is known to serve as an entry point for the SARS virus.
According to the research, SARS attaches itself to human cells in such a way that researchers found easy to break using medicine.
Unlike SARS, the COVID-19 strain attaches itself to human cells in a much more aggressive manner, meaning that its removal from a cell is much harder when compared to SARS.
Um eine Krankheit auszulösen, müssen Viren in Körperzellen eindringen. Dazu heften sie sich an geeignete Zellen an und schleusen ihre Erbinformation in diese Zellen ein. Infektionsforscher vom Deutschen Primatenzentrum – Leibniz-Institut für Primatenforschung in Göttingen haben zusammen mit Kollegen an der Charité – Universitätsmedizin Berlin untersucht, wie das neuartige Coronavirus SARS-CoV-2 in Zellen eindringt. Sie haben ein zelluläres Enzym identifiziert, das für den Eintritt des Virus in Lungenzellen unverzichtbar ist: die Protease TMPRSS2. Ein bereits existierendes Medikament, das diese Protease hemmt, könnte daher eine erfolgversprechende Behandlungsmöglichkeit darstellen (Cell).