Search for dangerous viruses now to prevent future pandemics

Most of what scientists know about viruses in animals is the list of nucleotides that make up their genomic sequence—which, while valuable, offers very little indication of a virus’s ability to infect humans.

Instead of letting the next outbreak catch the world by surprise, two virologists say at a Science Perspective article published today (March 10, 2023) that the scientific community should invest in a four-part research framework to proactively identify animal viruses that may infect humans.

“There’s been a lot of financial investment going into sequencing viruses in nature and thinking that from the sequence alone we’re going to be able to predict the next pandemic virus. And I think that’s just a fallacy,” said Cody Warren, an assistant professor of veterinary life sciences at Ohio State University and co-lead author of the article.

“Experimental studies of animal viruses will be invaluable,” he said. “By measuring the properties in those that are consistent with human infection, we can better identify the viruses that pose the greatest zoonotic risk and then study them further. I think that’s a realistic way to look at things that should also be considered.” .”

Warren co-authored the article with Sara Sawyer, a professor of molecular, cellular and developmental biology at the University of Colorado Boulder.

A key message that Warren and Sawyer want to get across is that knowing that an animal virus can attach to a human cell receptor does not give the full picture of its zoonotic potential.

They propose a series of experiments to assess the potential of an animal virus to infect a human: If it is found to enter human cells, can it use those host cells to make copies of itself and multiply? Once viral particles are produced, can they overcome human innate immunity? And has the human immune system ever been exposed to another virus from the same family?

Answering these questions could allow scientists to shelve a prozoonogenic virus candidate for further research—perhaps by developing a rapid way to diagnose the virus in humans if an unattributed illness occurs and testing existing antivirals as potential treatments. Warren said.

“What becomes difficult is that there may be many animal viruses out there with human compatibility signatures,” he said. “So which of these do you pick and choose to prioritize for further study? That’s something that needs to be carefully considered.”

A decent starting point, he and Sawyer suggest, would be working with the assumption that the viruses most dangerous to humans come from virus families that infect mammals and birds. These include coronaviruses, orthomyxoviruses (influenza), and filoviruses (which cause hemorrhagic diseases such as Ebola and Marburg). In 2018, Bombali virus—a new Ebola virus—was identified in bats in Sierra Leone, but its potential to infect humans remains unknown.

And then there are arterioviruses, such as the monkey hemorrhagic fever virus found in wild African monkeys, which Sawyer and Warren recently found has a decent chance of spreading to humans because it can replicate in human cells and reverse the ability of the immune cells to fight back.

The 2020 global lockdown to prevent the spread of COVID-19 is still a fresh and painful memory, but Warren notes that the dire effects of the SARS-CoV-2 outbreak could have been much worse. The availability of vaccines within a year of the lockdown was only possible because scientists had spent decades studying coronaviruses and knew how to attack them.

“So if we invest in studying animal viruses early and understand their biology in more detail, then in the event that they do show up in humans later, we’ll be better prepared to fight them,” Warren said.

“We will be constantly exposed to animal viruses. Things are never going to change if we stay on the same trajectory,” he said. “And if we get complacent and study these animal viruses only after they jump to humans, we’ll be constantly working backwards. We’ll always be behind.”