Two existing drugs inhibit SARS-CoV-2, the virus that causes COVID-19, from infecting human cells in the lab, a study has found. According to the study, published in the journal PNAS, both drugs, vacuolin-1 and apilimod, originally developed years ago, target a large enzyme called PIKfyve kinase.
Before this study, little was known about this enzyme's role in COVID-19 infection, the researchers said. The work, which will need to be replicated in human trials, suggests a potential new target for COVID-19 therapies, they said.
"Our findings show that targeting this kinase through a small-molecule antiviral against SARS-CoV-2 may be an effective strategy to lessen the progression or seriousness of COVID-19," said study co-senior author Tomas Kirchhausen, a professor at the Harvard Medical School (HMS) in the US. Kirchhausen said he discovered vacuolin-1 16 years ago, while apilimod was developed by a company called LAM Therapeutics.
Kirchhausen performed cell biology studies with SARS-CoV-2 virus in the lab of Sean Whelan, who had been part of the Center for Excellence team at HMS. "Within a week, we knew apilimod worked extremely well in preventing SARS-CoV-2 infection in human cells in the lab," said Kirchhausen, who initially published this discovery on the bioRxiv pre-print website in April 2020.
That pre-print also included a review of apilimod's effectiveness against Ebola and SARS-CoV-2. "We found that like apilimod, vacuolin-1 is a very strong inhibitor for viral infection in the lab," said Kirchhausen.
The HMS researchers noted that an unrelated group has published a paper in the journal Nature, showing that, in a screen of 12,000 clinical-stage or FDA-approved small molecules, apilimod was one of the best drugs for inhibiting SARS-CoV-2 virus replication.
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