Center for Drug Design and Texas A&M receive NIH grant to research Mpox treatment

The CDD team discussing the Mpox project. From left to right: Dr. Syafiq Shahari, Dr. Nirosh Udayanga, Dr. Ajit Jagtap, Dr. Won Hee (Harry) Ryu, Dr. Samuel Offei, and Dr. Zhengqiang (ZQ) Wang.

A $3.8 million National Institutes of Health (NIH) grant will fund research led by the University of Minnesota Center for Drug Design (CDD) in collaboration with Texas A&M University aiming to create antiviral drugs for the treatment of Mpox. 

Previously known as “monkeypox,” a misnomer born from scientists’ initial identification of the disease in captive lab monkeys in 1958, Mpox is typically associated with a painful rash.¹ The causative agent, MPXV, is generally classified into two types: clade I and clade II.² Clade I has been historically endemic to Central Africa and is more deadly. The less severe clade II perpetuated the 2022 outbreak of cases in the U.S. The virus belongs to the Orthopoxvirus genus, the same family as Smallpox, which the World Health Organization declared eradicated in 1980.³ But whereas Smallpox has two FDA-approved drugs for treatment, Mpox currently has none— neither of the approved Smallpox drugs, tecovirimat and brincidofovir, is known to be effective against Mpox, said the principal investigator Dr. Zhengqiang Wang, professor and co-director at the CDD. In clinical trials, tecovirimat did not resolve the main symptoms more quickly when compared with a placebo and the clinical efficacy of brincidofovir against Mpox remains unknown. The other key difference between the two— Smallpox is a human-specific disease, while Mpox is zoonotic, transmittable between animals and humans. This makes it nearly impossible to eradicate.  

“The bottom line is, there's a need [for a Mpox treatment] because the current two approved drugs against smallpox do not work— or we don't have evidence that they work,” Wang said. “That's the reason why we need new antiviral drugs, preferably with a different mechanism of action.”

The collaborative team of researchers, led by principal investigators Wang and Dr. Zhilong Yang at Texas A&M University, is examining three chemically-distinct antiviral compounds to understand how they work against Mpox. Two are from the known compound library— one is already an FDA-approved drug— and one of which they aim to develop into a topical drug. The third is currently their top priority: an in-house, synthetic compound developed in Wang’s lab. 

“It’s a compound we synthesized for other purposes over the years and it showed a very strong antiviral effect,” Wang said. “We expect to have a few very potent, very well characterized antiviral leads with great drug-like properties and great safety profiles.” 

To do that, the team first designs and synthesizes many analogs, testing them in cell cultures using vaccinia virus as a surrogate (MPXV’s “less evil cousin,” Wang calls it) to identify improved compounds. This measure is used because MPXV is a biosafety level three virus—high by safety standards— but once strong antiviral compounds are identified, they test them against the actual virus. 

“You basically infect cells with the virus and look at how the compound impacts the viral replication,” Wang explained. “After we do all the cell-based antiviral work, we will put the selected compounds in animal models to see how effective they are.”

The team’s collaborator in the Center for Disease Control is among the few groups with an effective animal model for Mpox, Wang said. An effective model will need to serve as both an infectious model to study how much the virus is reduced by the drug compounds and a disease model, where the animal will develop human-like, clinical symptoms. 

The work of Wang and his team has already drawn attention from various parts of the scientific community, such as pandemic-preparedness advocacy groups. Mpox generated plenty of public interest in the U.S. after the 2022 outbreak, but this research could prove critical for multiple reasons. 

“[An effective treatment] will have a huge impact, not just on the United States, but also every part of the world,” Wang said. “We're targeting Mpox because it’s re-emerging, and there is a very good chance that there are other similar viruses...other unknown poxviruses that could emerge. These viruses are very similar, so if you develop a drug, it could be effective against all these other pox viruses. You're talking about pandemic preparedness.”

¹ U.S. Department of Health and Human Services. Centers for Disease Control and Prevention. About Mpox. Atlanta: U.S. Department of Health and Human Services, 2025.https://www.cdc.gov/mpox/about/index.html.

² U.S. Department of Health and Human Services. Centers for Disease Control and Prevention. Ongoing Clade II Mpox Global Outbreak. Atlanta: U.S. Department of Health and Human Services, 2025.https://www.cdc.gov/mpox/outbreaks/2022/index-1.html.

 ³ U.S. Department of Health and Human Services. Centers for Disease Control and Prevention. About Smallpox. Atlanta: U.S. Department of Health and Human Services, 2024.https://www.cdc.gov/smallpox/about/index.html.