A group of B.C. scientists has isolated three naturally occurring compounds — including one from Vancouver Island’s Barkley Sound — that prevent COVID-19 infections in human cells.
The team, headed by François Jean and co-author Jimena Perez-Vargas, investigated more than 350 compounds from natural sources such as plants, fungi and marine sponges to unlock their potential to create new antiviral drugs for use against COVID-19 and other pathogens.
The naturally occurring compounds, known as special metabolites, are used by species to communicate and defend themselves across a variety of ecosystems, from tropical reefs to more northern climes.
“For 40 years, we have been collecting these organisms from all over the world,” said Raymond Andersen, a professor in the University of British Columbia’s departments of chemistry and earth, ocean and atmospheric sciences who was involved in the study. “About half of the drugs in clinical use are produced by these special metabolites.”
Researchers bathed human lung cells in solutions made from the compounds. They then added an engineered strain of the SARS-CoV-2 virus that glows fluorescent green when it infects a cell.
Most human cells in the samples gave off a green glow — the more powerful the glow, the more infected the cell. But in the a handful of cases, the glowing was significantly muted: The compound appeared to be stifling infection.
Of the hundreds of samples from around the world, three of the compounds — all from Canada — killed 50 per cent of a viral infection, the study found.
“That’s sort of the sweet spot for drug development. You want them to be potent,” Andersen said.
The study results were published this month in the journal Antiviral Research.
All three of the compounds came from Canadian seas: alotaketal C from a sponge-dwelling bacteria found in Howe Sound; bafilomycin D from bacteria found in ocean sediments in Barkley Sound, on the west coast of Vancouver Island; and holyrine A from a bacteria found off the coast of Newfoundland.
The sponge-derived compound produced some of the most interesting results. Instead of targeting the virus, the metabolite appeared to reduce the availability of ACE2 receptors on the surface of human cells. Those are the places where the SARS-CoV-2 virus binds to human cells, like a key fitting into a lock.
The fewer cellular locks are available, the harder it is for a viral key to infect a human cell, Andersen said.
“It doesn’t kill the virus, it acts on the host cell,” he said. “It’s a mechanism of action nobody has seen before.”
If the lock-closing mechanism — still a working hypothesis — proves accurate, alotaketal C could represent a powerful blueprint for a broad-spectrum anti-viral drug.
The researchers have already tested the sponge compound on several Delta and Omicron variants of SARS-CoV-2. Because it trains human cells to protect themselves, Andersen said he expects it to have a similar effect on the “Kraken” strain of the virus.
And in another test, the Vancouver Island-sourced bafilomycin D was combined with the recently discovered COVID-19 antiviral molecule N-0385, producing “synergistic” results and “an extremely valuable” starting point to develop multi-drug regimens in the treatment of the BA.2 Omicron sub-variant, the study said.
This isn’t the first time marine special metabolites have shown they could help treat some of the world’s most concerning infectious diseases, Andersen said.
“Some of these compounds have already been tested against dengue and zika,” he said. “Some of them have really broad spectrum activity against other viruses.”
In the past, many of the natural compounds that have inspired drugs have come from tropical ecosystems, Andersen said. The latest find, he said, shows that biological diversity on any corner of the planet can lead to scientific breakthroughs.
“I find it very exciting,” Andersen said of the Canadian discoveries. “This shows you don’t have to go far. You can find these things on your doorstep if you know what you’re doing.
“These are resources that need to be protected.”
Andersen said they have already found a way to make a synthetic analogue of alotaketal C, one that’s more potent and can easily be replicated without diving to the ocean floor. The natural compounds from Barkley Sound and Newfoundland, meanwhile, have been replicated through a fermentation process.
“The next step is to make sure it works on animals,” Andersen said.
Factor in human trials and even the best-case scenario would require another six to eight years of development.
Regardless of how long it takes to develop a drug, Andersen said new broad-spectrum anti-viral drugs will always be needed. “We need to have these drugs in our back pocket.”
— With a file from the Vancouver Sun
