Can aprotinin be used to treat COVID-19?

An established drug – aprotinin – may be a potential treatment for COVID-19.

Since the SARS-CoV-2 pandemic began, medical researchers around the world have tried to study possible treatments for the novel coronavirus. Treatment of the disease with existing drugs has improved over the past six months, which is reflected in a decrease in the infectious mortality rate. However, the search for more effective drug treatments is still ongoing. As our understanding of the virus and its replication continues to improve, more drug intervention targets will be revealed. A new study published in the journal Cells examines one such target – aprotinin – as a treatment for COVID-19 (1).

Through detailed study of the SARS-CoV-2 virus, it has been shown that the virus binds to host cells using a spike protein. However, once attached, the virus needs host cell enzymes called proteases to cut the spike protein so that the virus can enter the cells. Understanding this protease-mediated cell entry has presented protease inhibitors as possible therapies for the treatment of SARS-CoV-2. One such protease inhibitor is aprotinin. This drug was previously used to prevent bleeding during surgery because it inhibits the protease enzyme that dissolves the clot.

However, researchers at universities in Canterbury, Hanover and Frankfurt investigated whether the effects of aprotinin as a protease inhibitor can be used to prevent the replication of the SARS-CoV-2 virus. They performed a number of laboratory experiments using various cell cultures, including bronchial epithelial cells.

Paired cultures were infected with the SARS-CoV-2 virus in either the presence or absence of the drug. Forty-eight hours after infection, virus growth was assessed. However, inhibiting virus replication is of little use if a drug is also destroying the host cells. Therefore, the researchers also assessed the viability of the cell cultures at different concentrations of aprotinin.

Aprotinin demonstrated the ability to inhibit the replication of three different SARS-CoV-2 strains and to lower genome levels up to 900-fold. Crucially, however, aprotinin was only effective if it was introduced before the virus entered. In an experiment in which aprotinin was introduced after a one hour adsorption period, it did not significantly inhibit the virus. The study also looked at another drug candidate, SERPINA1 / alpha-1-antitrypsin, however this drug did not show similar antiviral activity.

The success of aprotinin in in vitro studies shows that it holds promise as a potential treatment for COVID-19. It has been shown to be effective in reducing virus replication at concentrations that can be safely achieved therapeutically. However, there are still a number of questions that remain to be answered. First, can these results be replicated in laboratory studies on living things? The drug has been shown to work in cell cultures, but the next step is to demonstrate similar activity in animal models.

Second, the fact that its effectiveness appears to be dependent on the time of administration affects the potential usefulness of aprotinin. It may be useful in the early stages of the disease, but less useful in more established diseases.

Finally, aprotinin has been the subject of significant safety concerns than it has previously been used in humans. The authors suggest that aerosol use could be a way to minimize these concerns. Aerosol delivery would minimize aprotinin levels in the bloodstream and deliver the drug to the area where it is most needed.

This study is another in the growing list of promising research avenues for treating COVID-19. However, aprotinin still has a long way to go before it can be considered a safe and effective treatment for the SARS-CoV-2 virus.

Written by

Michael McCarthy

1. Bojkova D., Bechtel M., McLaughlin K.-M., McGreig J.E., Klann K., Bellinghausen C. et al. Aprotinin inhibits SARS-CoV-2 replication. Cells. 2020; 9 (11): 2377.

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