With the COVID-19 pandemic shows no signs of slowing down and effective vaccines probably years away, treating infected patients is a crucial and immediate concern. As scientists turn to existing drugs to find prospective candidates, a new study has discovered that an already approved protein-based drug has the potential to serve as a treatment for the SARS-CoV-2 coronavirus infection.
According to an international team of scientists, Aprotinin—a drug approved for treatment against influenza in Russia—was found to exhibit strong inhibitory activity against the novel coronavirus. The drug was found to be effective against the virus in different types of cells and against four of its isolates.
"An approved aprotinin aerosol may have potential for the early local control of SARS-CoV-2 replication and the prevention of COVID-19 progression to a severe, systemic disease," wrote the authors.
A New Purpose
Aprotinin belongs to a class of drugs known as protease inhibitors, who bind to viral proteases—enzymes involved in the breaking down of proteins—and inhibit the replication of viruses. It is also known as bovine pancreatic trypsin inhibitor (BPTI) and is derived from the lung tissues of bovines.
It is known to slow down the process of fibrinolysis—the process of preventing blood clots from becoming bigger—and is used to reduce bleeding during complicated surgeries such as those of the liver and the heart. The goal of its use is to lessen the final damage to the organ due to blood loss-caused.
Due to its antiviral actions, the drug has been tested against influenza viruses. Several studies have shown that the drug is effective against these viruses both in vivo and in vitro. In fact, aerosolized forms of Aprotinin currently have approval for the treatment of influenza in Russia.
Testing Activity Against SARS-CoV-2
For the study, the scientists tested the efficiency of Aprotinin against the virus. They tested the drug in different varieties of cell cultures that had been infected—Caco2, Calu-3, and primary bronchial epithelial cell air-liquid interface cultures.
The four viral isolates against which the drug was tested were: SARS-CoV-2/FFM1, SARS-CoV-2/FFM2, SARS-CoV-2/FFM6, and SARS-CoV-2/FFM7. In order to compare the effectiveness of Aprotinin against SARS-CoV-2, the inhibitory activity of another protein-based drug, SERPINA1/alpha-1 antitrypsin (Prolastin), was also tested.
Stopping the Coronavirus In Its Tracks
The authors discovered that Aprotinin was able to effectively act against the novel coronavirus. It was found to suppress the replication of SARS-CoV-2 by acting as an entry inhibitor. They posited that the drug caused this action probably by interfering with the SARS-CoV-2's activation by the enzyme TMPRSS2(Transmembrane protease, serine 2).
Additionally, the authors also suggest that Aprotinin may be able to compensate for the loss of protease inhibitors of the host cells that downregulated due to the infection. Prolastin, however, was unable to exhibit the same kind of anti-viral activity against the coronavirus.
As Aprotinin aerosols are already approved for treatment against influenza in Russia, testing it against COVID-19 can be readily done, the authors expressed. "The aprotinin aerosol has been reported to be tolerated extremely well in influenza patients. Hence, it may have a particular potential to prevent severe COVID-19 disease when applied early after diagnosis," said Prof. Martin Michaelis, a corresponding author of the study, in a statement.
