Brian Shoichet explains key findings of a new paper published in Science

Researchers have identified a biological mechanism that may help explain why many repurposed drugs (such as hydroxychloroquine) that appeared to be active antivirals against SARS-CoV-2 in cell lines were not ultimately effective when tested in human clinical trials.

The findings of this paper suggest that many of these repurposed drugs did not get their antiviral activity from expected mechanisms, but instead by inducing phospholipidosis, which can be a toxic state for cells if the drugs are given in high enough doses.

A simple assay can reveal the degree to which a drug induces phospholipidosis, offering a simple way to assess the likelihood that a drug is acting through a truly antiviral mechanism. This would enable scientists to prioritize compounds that should be pursued in clinical trials potentially saving time and money in the search for effective antiviral treatments.

This work, led by Brian Shoichet, Tia Tummino, Veronica V. Rezelj, Benoit Fischer, and Audrey Fischer was done in collaboration with the labs of Marco Vignuzzi, Adolfo Garcia-Sastre, Kevan Shokat, Nevan Krogan, and Francois Pognan and Francesca Moretti of Novartis, among others.