The team showed that tylorone, quinacrine, and pyronaridine were effective in inhibiting SARS-CoV-2 replication. in vitro.
The research team found that three commonly used antiviral and antimalarial drugs were effective in preventing SARS-CoV-2 replication. in vitro. According to the researchers, the paper also underscores the need to test compounds at multiple cell lines to rule out false-negative results.
The team, which included researchers from North Carolina State University (NC State), USA and Collaborations Pharmaceuticals, studied three antiviral drugs that have been shown to be effective against Ebola and Marburg virus: tylorone, quinacrine and pyronaridine.
“We were looking for compounds that could block the virus from entering the cell,” said Ana Puhl, a senior scientist at Collaborations Pharmaceuticals and co-correspondent of the study. “We chose these compounds because we know that other antiviral drugs that work successfully against Ebola are also effective inhibitors of SARS-CoV-2.”
The compounds were tested in vitro against SARS-CoV-2, as well as against cold virus (HCoV 229E) and murine hepatitis virus (MHV). The researchers used a variety of cell lines that represented potential targets for SARS-CoV-2 infection in the human body. They infected the cell lines with various viruses, and then looked at how well the compounds prevent viral replication in cells.
The results were mixed, and the effectiveness of the compounds depended on whether they were used in human-derived cell lines relative to monkey-derived cell lines, known as Vero cell lines.
“In human cell lines, we found that all three compounds acted similarly to remdesivir, which is currently used to treat COVID-19,” said Associate Professor Frank Scholle of NC and co-author of the study. “However, they were not effective at all in Vero cells.”
“Researchers saw similar results when these compounds were first tested for Ebola,” said Sean Ekins, CEO of Collaborations Pharmaceuticals and co-author of the study. “They were efficient 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 testing. In other words, different cell lines may have different reactions to a compound. Indicates the need to test compounds in many different cell lines to rule out false negatives. “
The next steps of the research include examining the efficacy of the compounds in a mouse model and further work on understanding how they inhibit viral replication.
“One of the more interesting findings here is that these compounds not only prevent the virus from potentially binding to cells, but can also inhibit viral activity because these compounds act on lysosomes,” Puhl said. “Lysosomes, which are important for the normal functioning of cells, are abducted by the virus to enter and exit the cell. Thus, if this mechanism is disrupted, it cannot infect other cells. “
“Interestingly, these compounds are not only effective against SARS-CoV-2, but also against related coronaviruses,” Scholle said. “It could give us an advantage in therapy as new coronaviruses emerge.”
The study was published in ACS Omega.