[Editor’s note: This article is part of a Tyee partnership with Victoria-based Hakai Magazine, which is publishing stories about COVID-19 in these pages during the pandemic.]
Researchers in British Columbia are joining the international effort to find drugs that can treat the symptoms of COVID-19, contributing to both long- and short-term efforts to fight the pandemic.
One team has been granted nearly C$1 million to search through vast chemical libraries to find the basis for potential new medicines that specifically target the new coronavirus. That’s the sort of work that will take years to pan out, but could eventually find the most effective and side effect-free treatment.
At the other end of the spectrum, another team is investigating drugs that are already used for other conditions that might also prove useful against COVID-19.
The first group, led by Artem Cherkasov, a professor of urological sciences at the University of British Columbia, has a track record of developing drugs to treat prostate cancer. Cherkasov’s team has received $999,000 from the federal government’s new fund for COVID-19 research.
The team recently developed an artificial intelligence algorithm designed to trawl through massive databases of chemical compounds looking for proteins that might “dock” with a particular target — from viruses to cancerous cells. In February, after Chinese researchers identified the structure of COVID-19’s main receptor, a feature crucial to the virus’s ability to reproduce, the team turned their attention from cancer to the new coronavirus. The Chinese researchers found the lock, Cherkasov says: “We had to find a key.”
Already they have scanned through 1.3 billion compounds and found 1,000 that hold promise. Now they’ve whittled that list down to their top 100 favourites, and have ordered those chemicals for testing. “They’re in the mail,” says Cherkasov. It will take a few weeks for those compounds to arrive, he says, and meanwhile his co-workers are setting up a new lab to test them safely against COVID-19. “They wear protective suits and masks and work in a proper environment. I’m not allowed in those labs,” he laughs. “I’m a computer guy.”
“Realistically within a month we will have some answers, in an optimistic scenario,” Cherkasov says.
Even with a promising compound, however, it will take much more work to turn it into an actual drug; including animal and human testing that will take years. “We’re in a race against time, but we know what we’re doing,” he says.
If none of the compounds hold promise, there’s plenty more to examine, Cherkasov says: some databases contain up to 13 billion compounds.
Cherkasov’s approach is useful says Alpha Lee, the chief science officer for PostEra, a machine-learning medicine company. PostEra is leading its own non-profit effort to find candidates for new drugs. Instead of scouring databases of known compounds, they are asking chemists to invent new chemicals by stitching together fragments already shown to bind to the virus that causes COVID-19. So far, the crowdsourcing effort has received 2,000 submissions. “Our hope is we can deliver some drug candidates within months,” says Lee.
Finding or inventing a new drug would have the benefit of being highly specific to the particular proteins on the new coronavirus’s cells, so the drug would theoretically be very effective and have minimal side effects. But developing new drugs takes time. Checking the efficacy of existing drugs is much, much faster.
On March 20, the World Health Organization announced a multi-country mega-trial, called Solidarity, of existing treatments identified as the most promising against COVID-19. The short list includes the antiviral remdesivir; the malaria drugs chloroquine and hydroxychloroquine; a cocktail of the HIV drugs lopinavir and ritonavir; and one other known drug. Other research teams are frantically pursuing other avenues, including examining the potency of favipiravir, a flu drug, and various arthritis drugs.
James Russell, lead investigator at the Centre for Heart Lung Innovation at St. Paul’s Hospital in Vancouver, received a grant for $255,970 to look at a class of drugs called angiotensin II receptor blockers, or ARBS, commonly prescribed for high blood pressure and diabetes. These drugs were mired in controversy in recent weeks with some experts arguing that they may increase people’s susceptibility to COVID-19, while others suggest they might decrease the risk of pneumonia by reducing lung injury caused by the infection.
Russell’s team plans to look at 497 adult patients in B.C. hospitals to assess if and how ARBs affect COVID-19.
Cherkasov argues that if any known drugs worked, they would have already made an impact. “From where I stand, we need something new.”
Lee, however, says that any and all efforts are welcome at this point. “We are starting from the bottom up, trying to build a drug from pieces. Artem [Cherkasov] is scoring existing molecules. Others are tackling existing drugs,” says Lee.
“To crack this problem as soon as possible, we need all three approaches.”