A recent study has shown that aprotinin, a drug that reduces the risk of bleeding during surgery, can stop the novel coronavirus from entering host cells. The drug could serve to prevent severe cases of COVID-19, the authors say.
With a number of vaccines on the way, there is now light at the end of the tunnel in the COVID-19 pandemic.
Although the introduction of an effective vaccine may allow life to return largely to normal, the eradication of SARS-CoV-2 is unlikely. Humanity is probably going to have to live with the virus, which may eventually become seasonal.
Therefore, treatments will still be necessary in cases where people do contract the virus and develop COVID-19. Treatments are also important in concert with vaccine development, as no vaccine is 100% effective.
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Although there are not yet any approved medications that can cure or even prevent COVID-19, several treatments have been under investigation, including the experimental Ebola drug remdesivir.
A new study that researchers at Goethe University Frankfurt, Germany, led has shown that the anti-bleeding drug aprotinin (Trasylol) can stop SARS-CoV-2 from entering host cells. The authors say that aprotinin could prevent COVID-19 from progressing to a severe, systemic disease.
The findings appear in the journal Cells.
The protease step
Aprotinin is an inhibitor of fibrinolysis, the process leading to the breakdown of blood clots. Doctors sometimes use it during surgery to reduce the risk of bleeding and, consequently, the need for blood transfusions.
Aprotinin is also a protease inhibitor, which is important in the context of COVID-19.
This is because cleavage of the coronavirus spike protein — which a protease performs — is an essential step in the viral life cycle, allowing the virus access to cells in the body. This cleavage must take place for the virus to be able to bind to its receptors on the surface of our cells.
To investigate whether aprotinin could prevent this critical step, and thereby stop the virus from entering cells, the team behind this study performed various experiments in cells.
Cell culture experiments
The researchers added aprotinin to cells both before and after they infected them with the virus. The results showed that aprotinin effectively prevented the virus from entering the cells (and, therefore, from replicating) in both cases.
The testing process involved various cell types, including cells isolated from the surface of human bronchi, and a range of concentrations of aprotinin. The team also tested the drug against three different strains of the virus outside of cells.
Importantly, the results showed that aprotinin was effective in inhibiting the virus at levels that doctors could realistically give to a patient (i.e., at therapeutic doses).
“Our findings show that aprotinin is effective against SARS-CoV-2 in concentrations that can be achieved in patients,” comments senior author Prof. Jindrich Cinatl, a professor at the Institute for Medical Virology at the University Hospital Frankfurt.
Therapeutic precedent
If aprotinin gets approval for use as a COVID-19 treatment, doctors could use it to prevent severe cases of the disease from developing by suppressing levels of the virus and preventing lung injury.
The team is hopeful that it would be possible to roll aprotinin out to the patient population relatively quickly, as it is already approved for similar uses. The drug could potentially also treat respiratory infections with similar viruses.
“In aprotinin, we have a drug candidate for the treatment of COVID-19 that is already approved for other indications and could readily be tested in patients.”
– Prof. Cinatl
In Russia, an aerosol form of aprotinin has received approval for the treatment of flu, which shares similarities with COVID-19. Influenza viruses use proteases to gain entry to host cells in a similar way to SARS-CoV-2.
However, scientists must carefully consider the side effects, particularly in relation to blood clots, before giving the drug to patients. It is not yet clear whether aprotinin would reduce or promote blood clotting in people with COVID-19.
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