Health
Three commonly used antiviral drugs that are potentially effective in preventing SARS-CoV-2 replication
An international team of researchers found that three commonly used antiviral and antimalarial drugs are effective in vitro to prevent replication of SARS-CoV-2, the virus that causes COVID-19. discovered. The study also emphasizes the need to test compounds against multiple cell lines to rule out false-negative results.
A team of researchers from North Carolina State University and Collaborations Pharmaceuticals examined three antiviral drugs that have been shown to be effective against Ebola and Marburg viruses: tyrolone, quinacrine, and pyronalidine.
“We were looking for a compound that could block the virus from entering cells,” said Ana Puhl, senior scientist and co-author of the study at Collaborations Pharmaceuticals. “We chose these compounds because we know that other antiviral drugs that work well against Ebola are also effective inhibitors of SARS-CoV-2.”
The compounds were tested in vitro against SARS-CoV-2 and the common cold virus (HCoV 229E) and mouse hepatitis virus (MHV). Researchers have utilized a variety of cell lines that are potential targets for SARS-CoV-2 infection in the human body. They infected the cell lines with various viruses and then investigated how well the compounds prevented viral replication in the cells.
The results are mixed and the effectiveness of the compound depends on whether it was used in a monkey-derived cell line known as the Vero cell line or a human-derived cell line.
“In human-derived cell lines, we found that all three compounds functioned similarly to remdesivir, which is currently used to treat COVID-19,” said North Carolina State University’s associate professor and co-author of the study. Frank Chollre said. .. “But they had no effect on Vero cells.”
When these compounds were first tested against Ebola, researchers saw similar results. 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, different cell lines can respond differently to the compound. It indicates the need to test compounds in many different cell lines to rule out false negatives. “
Sean Ekins, CEO of Collaborations Pharmaceuticals and co-author of the study
The next steps in the study will include testing the effectiveness of the compounds in mouse models and further work to understand how they inhibit viral replication.
“One of the more interesting findings here is that not only do these compounds prevent the virus from binding to cells, but they also act on lysosomes, which can inhibit viral activity. That’s what it is, “says Puhl. “Lysosomes, which are important for normal cell function, are hijacked by the virus to enter and leave cells, so if that mechanism is disrupted, they cannot infect other cells.”
“It is also interesting that these compounds are effective not only against SARS-CoV-2 but also against related ones. Coronavirus“When a new coronavirus emerges, it may give us a favorable start to treatment,” says Scholle.
Source:
Journal reference:
Pull, AC, et al. (2021) Diversion of the Ebola and Marburg virus inhibitors tyrolone, quinacrine, and pyronalidine: in vitro activity and potential mechanism for SARS-CoV-2. ACS Omega. doi.org/10.1021/acsomega.0c05996..
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