Synergistic inhibition of SARS-CoV-2 Omicron (BA.2) infection by the combined use of bafilomycin D and N-0385. Inhibition dose-response curves of single and combination treatment of bafilomycin D and N-0385 in SARS-CoV-2-infected Calu-3 cells were used for analysis using the open source SynergyFinder web application. A) Dose-response matrix (percent inhibition) of SARS-CoV-2 infection with combination therapy of bafilomycin D and N-0385. B) Synergy distribution of the pairwise combination of bafilomycin D and N-0385 calculated based on Loewe’s additive model using SynergyFinder. C) Landscape visualization between bafilomycin D and N-0385 calculated based on Loewe’s additive model using SynergyFinder. The surface is color coded, with red indicating synergistic interactions and green indicating antagonistic interactions. Credit: antiviral research (2022). DOI: 10.1016/j.antiviral.2022.105484
UBC researchers have identified three compounds that prevent COVID-19 infection in human cells, derived from natural sources, including a BC marine sponge.
The discovery paves the way for the development of new drugs for COVID-19 variants made from natural sources. And given the abundance of nature, there could be a host of new antivirals waiting to be discovered.
In a recent study, an international team of researchers led by UBC scientists investigated a catalog of more than 350 compounds derived from natural sources, including plants, fungi and sea sponges, in an attempt to find new antiviral drugs that could be used to treat COVID-19. 19 variants as omicron.
“This interdisciplinary research team is unraveling the significant possibilities of biodiversity and natural resources and uncovering nature-based solutions to global health challenges like COVID-19,” said lead author Dr. François Jean, Professor associate in the department of microbiology and immunology.
By bathing human lung cells in solutions made with these compounds and then infecting them with SARS-CoV-2, the researchers found 26 compounds that completely reduced viral infection in the cells. Three were effective in very small doses.
“The advantage of these compounds is that they target cells, rather than the virus, blocking virus replication and helping the cell to recover,” said co-lead author Dr. Jimena Pérez-Vargas, a research associate at the department. microbiology and immunology. “Human cells evolve more slowly than viruses, so these compounds could work against future variants and other viruses like influenza if they use the same mechanisms.”
The researchers used a version of the SARS-CoV-2 virus that makes cells glow fluorescent green when infected, as well as a special detection technique, to identify the top 26 natural compounds that showed inhibition of COVID-19 infection. 19 with low cell damage. . The fluorescent virus is a powerful tool, said co-author Dr. Tirosh Shapira, a postdoctoral fellow in the medical school.
“With it, experimentally laborious steps become redundant so that we can quickly and easily check thousands of compounds. Even more important, with it we have the option to track SARS-CoV-2 ‘live’ as it spreads.” from one cell to another. “
The three most effective compounds were found in Canada: alotaketal C from a marine sponge collected in Howe Sound, BC, bafilomycin D from a marine bacterium collected in Barkley Sound, BC, and holyrine A from marine bacteria collected in Newfoundland waters.
“We’ve been collecting things for 40 years around the world, but these three are Canadian and two are from British Columbia,” said co-author Dr. Raymond Andersen, a professor in the chemistry department.
Additional tests showed that all three compounds were effective against the delta variant and several omicron variants, and are as safe for human cells as current COVID-19 treatments. Many of these treatments are no longer effective against currently circulating omicron variants because the virus is evolving. This highlights the need for new antivirals, Dr. Jean said.
Working together with other antivirals
The researchers explored how effective the compound bafilomycin D was when used in combination with a recently discovered COVID-19 antiviral, the molecule N-0385. They found that the compound and molecule worked synergistically against the omicron BA.2 subvariant. This suggests a promising starting point for developing omicron variant multidrug therapies that are effective in treating COVID-19 and other viruses, Dr. Jean said.
The researchers plan to test the compounds in animal models in the next six months. “Our research also paves the way for large-scale testing of natural product medicines that can block infection associated with other respiratory viruses of major concern in Canada and around the world, such as influenza A and RSV,” said Dr. . Jean.
The article is published in the magazine antiviral research.
Jimena Pérez-Vargas et al, Discovery of leading natural products to develop pan-SARS-CoV-2 therapies, antiviral research (2022). DOI: 10.1016/j.antiviral.2022.105484
Provided by the University of British Columbia
Citation: Sea Sponge Has COVID Blocking Powers (2023, Jan 9) Retrieved Jan 9, 2023 from https://phys.org/news/2023-01-sea-sponge-covid-blocking-powers.html
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