Commonly Used Antiviral and Anti-Malarial Drugs Found to Work Similarly to Gilead’s Remdesivir in Preventing SARS-CoV-2 Replication

Researchers have found that three commonly used antiviral and antimalarial drugs which work similarly to Gilead Sciences’ (Foster City, CA, USA) antiviral drug remdesivir are effective in vitro at preventing replication of SARS-CoV-2, the virus that causes COVID-19.

The work by an international team of researchers, including from NC State University (Raleigh, NC, USA), also underscores the necessity of testing compounds against multiple cell lines to rule out false negative results. The researchers looked at three antiviral drugs that have proven effective against Ebola and the Marburg virus: tilorone, quinacrine and pyronaridine.

The compounds were tested in vitro against SARS-CoV-2, as well as against a common cold virus (HCoV 229E) and murine hepatitis virus (MHV). Researchers utilized a variety of cell lines that represented potential targets for SARS-CoV-2 infection in the human body. They infected the cell lines with the different viruses and then looked at how well the compounds prevented viral replication in the cells.

The results were mixed, with the compounds’ effectiveness depending upon whether they were used in human-derived cell lines versus monkey-derived cell lines, known as Vero cell lines. The next steps for the research include testing the compounds’ effectiveness in a mouse model and further work on understanding how they inhibit viral replication.

“In the human-derived cell lines, we found that all three compounds worked similarly to remdesivir, which is currently being used to treat COVID-19,” said Frank Scholle, associate professor of biology at NC State and co-author of the research. “However, they were not at all effective in the Vero cells.”

“One of the more interesting findings here is that these compounds don’t just prevent the virus from potentially binding to the cells, but that they may also inhibit viral activity because these compounds are acting on the lysosomes,” said Ana Puhl, senior scientist at Collaborations Pharmaceuticals and co-corresponding author of the research. “Lysosomes, which are important for normal cell function, are hijacked by the virus for entry and exit out of the cell. So, if that mechanism is disrupted, it cannot infect other cells.”

“It’s also interesting that these compounds are effective not just against SARS-CoV-2, but against related coronaviruses,” added Scholle. “It could give us a head start on therapies as new coronaviruses emerge.”

Related Links:
NC State University
Gilead Sciences