Groundbreaking research out of the University of Alberta (U of A) shows why the antiviral drug remdesivir works against some viruses but not others, a key discovery in the battle against future pandemics.
The research paper, recently published in the Journal of Biological Chemistry, reveals how the drug remdesivir — given to more than nine million COVID-19 patients worldwide — works against different families of viruses.
Researchers say that before now, it was not understood why remdesivir works in lab tests against some viruses including coronaviruses, Ebola, hepatitis C and Nipah virus, but not against others, like the flu.
Matthias Götte, professor and chair of medical microbiology and immunology at the U of A, noted that it all comes down to how well the drug tricks the polymerase, which is the replication engine of the virus and the target of remdesivir.
“Remdesivir is very well incorporated by the polymerase of SARS-CoV-2 and not so well by other viruses where it does not work,” he said in a recent U of A press release, adding that once it is incorporated, the drug inhibits all viral polymerases tested in the study.
The next step for researchers is to modify the compound to be better accepted by the polymerase of a broader range of other viruses.
“What we would like to have when the next pandemic strikes — and it’s not a question of if, it’s a question of when — what we need to have on the first day is a broad-spectrum antiviral agent,” Götte said.
Another key to successful antivirals is timing, with clinical trials showing that remdesivir cuts the risk of hospitalization by 87 per cent when given early on. Götte adds that because it is currently only available intravenously, remdesivir is sometimes given too late to have its full effect. The United States and Europe recently recommended remdesivir for early use in outpatients with mild to moderate disease, and Götte hopes Canada will follow suit.
Götte notes that the new Pfizer oral antiviral drug approved just last week by Health Canada appears to be as effective as remdesivir at preventing hospitalizations when given early. Another orally available antiviral drug, molnupiravir, has also recently been given FDA approval for use against COVID-19 in the United States; it appears to prevent only about 30 per cent of hospitalizations but also shows activity against other viruses, including the flu.
Götte believes the more antiviral options available, the better. If a new virus strikes, it will take time to develop a vaccine, and treatments are needed in the meantime. The ideal situation would be to treat patients with more than one antiviral at a time.
“When you combine antiviral drugs, it is more efficacious, more potent, and you reduce the likelihood of the virus developing resistance to any one drug,” he said.