Jeffrey Glenn granted $14.3 million to develop broad spectrum drugs

The Stanford researcher is pursuing antiviral drugs with broad efficacy against enteroviruses, which cause common colds and polio, and coronaviruses including the one that causes COVID-19.

- By Bruce Goldman

Jeffrey Glenn

Jeffrey Glenn, MD, PhD, professor of gastroenterology and hepatology and of microbiology and immunology, has won a five-year, $14.3 million contract from the National Institute of Allergy and Infectious Diseases to fund development of broad-spectrum antiviral drugs for enteroviruses and potentially SARS-CoV-2.

The contract could be renewed for up to $47.8 million if all milestones are met and NIAID decides to fund all possible options.  

Enteroviruses constitute a broad family of viruses. They’re responsible for about half of the mild viral upper-respiratory infections known as the common cold, as well as encephalitis and myocarditis — inflammation of the brain and the heart, respectively — and the poliovirus.  

Since 2014, another enterovirus, EV-D68, has been implicated in puzzling biennial bursts of a polio-like disease, acute flaccid myelitis, in the United States and Europe. 

Of particular interest for Glenn are possible drug targets in the host cells upon which viruses depend.

“Our first targeted indication will be EV-D68, a devastating cause of paralysis in children and fatal sepsis in neonates,” he said. “There is no Food and Drug Administration-approved therapy for EV-D68, but our small-molecule inhibitors are the only ones to date to have shown efficacy in animal models of enteroviruses, where we have achieved 100% survival and even reversal of paralysis.” 

Glenn is also pursuing antiviral drugs directed against SARS-CoV-2, the virus that causes COVID-19. 

“In my lab at Stanford, we’ve developed two very compelling possible therapies for other viruses that, it turns out, are directly applicable to SARS-CoV-2,” he said. “In both cases, we’ve demonstrated in vivo efficacy in animal models.” One of the potential therapies is the small molecule inhibitor of EV-D68. 

“Importantly, the target of our drug has already been implicated as part of the mechanism of how coronaviruses enter cells,” Glenn said. “So my great team and I are trying to repurpose it for COVID-19.”

Because they target a host cell function upon which multiple viruses depend, Glenn said, “our molecules have a high barrier to the development of resistance and are highly active against a range of other viral pathogens, including SARS-CoV-2. These efforts can also help us be more proactive — as opposed to reactive — with respect to the next pandemic.”

Glenn is a member of Stanford Bio-X and of the Stanford Maternal & Child Health Research Institute and is a faculty fellow of Stanford ChEM-H.

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2023 ISSUE 3

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