As COVID continues to mutate, Rutgers team develops possible alternative to Paxlovid

When the highly contagious omicron variant of COVID-19 surged in December 2021, filling intensive care units in New Jersey and across the U.S., federal regulators gave emergency authorization to the medication Paxlovid to combat the virus.

And it worked. Scientists and physicians credit the anti-viral medicine as a major achievement in the battle against COVID and its many variants, because it reduced the severity of symptoms and prevented hospitalizations and deaths, especially in older people and those with underlying conditions.

But viruses mutate.

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And with mutation comes the ability for a virus to become resistant to drugs that have worked well in the past.

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Now a team of Rutgers scientists has developed a compound they believe could be the next anti-COVID medication. Lab results and early research on COVID-infected mice show that the drug, called a “viral papain-like protease inhibitor,” slows disease progression.

Variants resistant to Paxlovid

“It’s just a matter of time that variants resistant to Paxlovid emerge,” said Jun Wang, who leads the project and runs a research lab at the Rutgers School of Pharmacy. “It’s not happening now, but as scientists, we want to be prepared ahead of time.”

Paxlovid remains the go-to drug when symptoms are detected early, because it stops the COVID virus from entering uninfected cells, thus minimizing its spread.

Paxlovid still remains the go-to drug when symptoms are detected early, because it stops the COVID virus from entering uninfected cells, thus minimizing its spread.

This winter’s COVID season has been similar to last year’s in terms of severity — both mild compared with prior outbreaks that saw upward of 5,000 to 6,000 hospitalizations per day. On Tuesday, 53 patients with COVID were on ventilators and 181 were in intensive care at New Jersey hospitals, according to state Health Department data.

No significant COVID mutation lately

COVID has yet to make a significant mutation in the past few years, as all of the dominant strands have been subvariants of omicron, against which Paxlovid is very effective. As of the first week in January, all 11 COVID variants circulating in New Jersey were subvariants of omicron, including the emerging JN.1 variant.

But shortly after the pandemic began in late 2019, scientists across the globe began studying how COVID mutates and what that means for prevention and treatment. Paxlovid has already been seen to lose effectiveness among immunocompromised patients when the virus persists for months and mutates as it replicates, according to a study by Columbia University and several Chinese schools.

Wang’s team set out three years ago to make a drug that could disrupt a protein essential to many functions in all known COVID strains. They were aided by researchers from the Arnold Lab at Rutgers’ Center for Advanced Biotechnology and Medicine, who were able to map the structure of the virus’s protein.

Disrupting an essential COVID protein

The Rutgers team created 85 compounds that would bond to the protein. After testing each one in the laboratory, they found that the best of the bunch was a compound — Jun12682 — that inhibited several strains of the virus, including those seemingly immune to Paxlovid.

The compound was shipped to collaborators at Oklahoma State University, who tested it on the infected mice. Results show that it reduced the amount of virus in the mice and the survival rate skyrocketed.

The compound is still in its infancy. Although the findings have been published, they still need to be peer-reviewed by other scientists to ensure the process was carried out correctly and the results are accurate.

And then there is the hunt for a drugmaker that has the financial backing to fund costly clinical trials that, if successful, may eventually lead to FDA approval.

“It is not our intention to develop this as a replacement for Paxlovid but more of a backup to fill in the gaps,” Wang said. “We’ll have a drug on the shelf ready to go for the next pandemic.”

This article originally appeared on NorthJersey.com: As COVID continues to mutate, Rutgers team develops possible alternative to Paxlovid