Three commonly used antiviral drugs that may be effective in preventing the reproduction of SARS-CoV-2

An international team of researchers has discovered that three used antiviral and antimalarial drugs are effective in vitro in preventing the reproduction of SARS-CoV-2, the virus causing COVID-19. The work also reinforces the need to test fertilizers against multiple cell lines to rule out false negative results.

The team, which included researchers from North Carolina State University and Collaborations Pharmaceuticals, looked at three antiviral drugs that have been shown to be effective against Ebola and the Marburg virus: tilorone, quinacrine and pyronaridine.

“We were looking for a fertilizer that could prevent the virus from entering the cell,” said Ana Puhl, senior scientist at Collaborations Pharmaceuticals and corresponding author of the study. “We chose these fertilizers because we know that other antivirals that successfully fight Ebola are also effective inhibitors of SARS-CoV-2.”

The fertilizers were tested in vitro against SARS-CoV-2, as well as against the common cold virus (HCoV 229E) and murine hepatitis virus (MHV). Researchers used several cell lines that represented potential targets for SARS-CoV-2 infection in the human body. They lined the cell lines with the various viruses and then looked at how well the fertilizers prevented viral reproduction in the cells.

The results were mixed, with the effectiveness of the fertilizers depending on whether they were used in human-derived cell lines versus monkey-derived cell lines, known as Vero cell lines.

“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 related to biology at NC State and co-author of the research. “However, they were not effective at all in the Vero cells.”

Researchers saw similar results when these fertilizers were first tested against Ebola. They were effective in human-derived cell lines, but not in Vero cells. This is important because Vero cells are one of the standard models used in this type of test. In other words, a combination of cell lines may have different responses. It highlights the need to test fertilizers in multiple cell lines to rule out false positives. “

Sean Ekins, Head of Collaborations Pharmaceuticals and corresponding author of the research

The next steps for the research include testing the effectiveness of fertilizers in a mouse model and further work on understanding how they inhibit viral reproduction.

“One of the most interesting results here is that these fertilizers not only prevent the virus from attaching to the cells, but may also inhibit viral activity because these fertilizers are works on the lysosomes, “Puhl says.” Lysosomes, which are important for normal cell function, are removed by the virus to get in and out of the cell. Therefore, if that equipment is disturbed, it cannot capture other cells. “

“It is also interesting that these fertilizers are effective not only against SARS-CoV-2, but against associated coronaviruses,” Scholle says. “It could give us a head start on treatments as new coronaviruses appear.”