Three new antiviral and antimalarial drugs that effectively prevented the replication of SARS-CoV-2, the virus that causes COVID-19, in the laboratory, a new study shows.
The paper also emphasizes the need to test compounds on multiple cell lines to rule out false negative results.
The researchers studied antiviral drugs that have been shown to be effective against Ebola and the Marburg virus: tylorone, quinacrine, and pyronaridine.
“We were looking for compounds that could block the virus from entering the cell,” says Ana Puhl, a senior scientist at Collaborations Pharmaceuticals and co-author of the paper.
“We chose these compounds because we know that other antiviral drugs that work successfully against Ebola are also effective inhibitors of SARS-CoV-2,” says Puhl.
The researchers tested the compounds in vitro against SARS-CoV-2, as well as against the common cold virus (HCoV 229E) and mouse hepatitis virus (MHV).
The team 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 the researchers used them 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,” says co-author Frank Scholle, an associate professor of biology at North Carolina State University. “However, they were not effective at all in Vero cells.”
“Researchers have seen similar results when these compounds were initially tested for Ebola,” says Sean Ekins, CEO of Collaborations Pharmaceuticals and co-author.
“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 potential binding of the virus to cells, but that they can also inhibit viral activity because these compounds act on lysosomes,” says Puhl.
“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,” says Scholle. “It could give us an advantage in therapy as new coronaviruses emerge.”
The paper appears in ACS Omega. Additional co-authors are from the Oswaldo Cruz Institute and Campinas University, both in Brazil; Utah State University; University of Maryland; and SRI International.
The National Institutes of Health and the State Institute of Comparative Medicine funded the work.
Source: NC State