Chemist aims at COVID-19 following success with related virus

Strand of mRNA illustration

Lab led by researcher Blanton Tolbert at Case Western Reserve partners with international scientists seeks expanded NIH support to ‘target virus at molecular level’

A team of scientists, including Case Western Reserve University chemistry Professor Blanton Tolbert and his research lab, are conducting the underlying research to develop an antiviral to slow the spread of novel coronavirus that causes COVID-19.

Tolbert said he and research partners from Duke and Rutgers universities hope to hear soon from the National Institutes of Health (NIH) whether their project to develop an antiviral against the novel coronavirus behind the global pandemic of COVID-19 will receive funding.

The research team recently laid the groundwork to develop novel antivirals against Enterovirus 71 (EV71), a similar RNA virus that causes hand, foot and mouth disease. Tolbert said they are now poised to make significant inroads into identifying vulnerable COVID-19 targets.

“We’ve already shown the necessary ‘proof of concept’ with EV71, which shows we know how to get things done,” Tolbert said. “And now we have assembled an expanded international group to include scientists from the University of Michigan, the United Kingdom and Taiwan, where they isolated some very early COVID-19 viruses from two infected patients at Chang Gung Memorial Hospital.”

Tolbert said that his Taiwanese collaborators have been able to clone the novel coronavirus in the lab, providing a copy to study at the molecular level-the first step in learning how it works.

Tolbert’s lab studies basic biochemical processes of ribonucleic acid (RNA) viruses, working to better understand the physical interactions between the virus and host. Their most recent work has determined the 3D structures of pieces of viruses from HIV and EV71, he said.

While EV71 is not a coronavirus, both fall under “the bigger umbrella of positive-sense RNA viruses that infect humans,” he said.

“And if you can figure out how the virus interacts with the cellular environment it has infected, where the real activity takes place, you can understand it better,” Tolbert said. “You can look at how it takes over the cellular machinery with the ultimate goal of making drugs to block those processes. But first you have to know how it hijacked the cells in the first place.”

Early start on coronavirus focus

It was still early February of this year when Tolbert sat in a conference room in Durham, North Carolina, with colleagues from Rutgers and host Duke University. They were meeting to celebrate their recent success with EV71 and to talk about next steps in publishing (their work is published on a pre-print site, but not yet in a named journal) and expanding their work on that particular virus.

But a new, still barely known novel virus, which had just appeared in Wuhan, China, was also on their minds.

China had just recently shared the genetic sequence of the novel coronavirus on Jan. 12, and soon the World Health Organization would declare a public health emergency of international concern over the global outbreak of the novel coronavirus, then referred to as nCoV.

So when Tolbert and his colleagues turned their attention and expertise toward COVID-19, they were ahead of the curve, he said. The NIH didn’t even announce for another two weeks that emergency funds to fight COVID-19 were available.

“We were already working on something for which there are no antivirals, something with high mortality and morbidity (illness and other conditions associated with the virus) rates-especially for children in Southeast Asia,” he said. “So when we saw the early signs that this coronavirus had no antivirals or vaccine, we decided to see how we might get involved, knowing we already had that proof-of-concept with this other virus.”

He said how quickly the research group hears from the NIH on whether it will get a new influx of funding to tackle COVID-19 will likely depend on whether the agency considers the work urgent enough-either for “flattening the curve,” the phrase for leveling out over time the rapidly rising number of cases, or finding a permanent antiviral.

“I cannot anticipate what is coming next,” he said. “This is something that needs to be done if an antiviral is going to be achieved. The bottom line is that we believe we are equipped and ready to go, and we can make a difference.

“I don’t know if that means it will lead directly to an antiviral yet, but I believe we can find ways to target this at the molecular level.”

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