Researchers at Rutgers University say they are showing early signs of progress toward a new treatment for COVID-19 that could work on future drug-resistant strains of the virus and represent a potential alternative to antivirals like Paxlovid.

No one knows when drug-resistant mutations of COVID-19 may emerge, said Jun Wang, an associate professor of medicinal chemistry who is leading the research.

“When it becomes a problem, we want to have something in hand,” he said. The Rutgers team is one of several around the world seeking alternatives to current treatments.

Paxlovid, the brand name for the medication combining the drugs nirmatrelvir and ritonavir, can reduce the risk of severe coronavirus symptoms. But Paxlovid has its limitations, including potential side effects when combined with some other medications.

Wang and his team recently published a pre-print of their research — meaning it still has to be reviewed by other scientists — showing they have developed a promising treatment option that significantly reduced the viral load in mice infected with COVID-19.

The molecule Wang’s team developed targets a different protein in the COVID virus than Paxlovid.

They tested it on strains of the virus that are already circulating as well as drug-resistant strains that were developed in a lab for research purposes, Wang said. It’s not uncommon for scientists to manipulate a virus to further their research, although the practice has come under greater scrutiny in the wake of COVID — particularly when scientists develop strains that are more virulent or infectious than what’s currently circulating.

Wang’s team was also able to show their treatment did not interfere with certain enzymes that help people metabolize drugs, suggesting it may not have the same interactions with other medications as Paxlovid, he added.

The real-world implications

The Rutgers research on drug interactions aims to create a COVID treatment that doctors would be more likely to prescribe.

Paxlovid significantly reduces the risk of hospitalization or death in those at high risk for a severe case of COVID-19, including older adults and who are immunocompromised, according to the Centers for Disease Control and Prevention.

But a recent study from the National Institutes of Health found that, out of about 1 million COVID patients who were eligible for Paxlovid between December 2021 and February 2023, only about 10% were treated with the drug.

A range of factors come into play when deciding whether to prescribe Paxlovid to a patient who has COVID, including their age and how healthy they are, said Dr. Aaron Glatt, chair of the medicine department and chief of infectious diseases at Mount Sinai South Nassau.

“Paxlovid shouldn't be given out like water,” he said.

If a patient is taking medication that could interact negatively with Paxlovid, Glatt said he would evaluate how serious a side effect it could produce and consider whether the other drug could be paused for a few days.

Glatt noted that a different COVID drug, remdesivir, doesn’t have the same issues but is only available through a shot rather than a pill.

Dr. Josh Fessel, one of the NIH researchers who worked on the study about Paxlovid uptake, said it's encouraging that scientists like Wang are looking for new COVID treatments that can stand up to future drug-resistant strains of the virus and may improve on existing treatment options in other ways.

Fessel said he has worked on an initiative within NIH that aims to accelerate the pace of COVID research, including on new treatments and existing FDA-approved drugs that could potentially be repurposed for COVID. So-called “peacetime research,” conducted between public health emergencies, is crucial to understanding and combating the virus, he said.

Other researchers have also developed alternatives to Paxlovid, including some antivirals intended for people who are young and healthy — but so far none have made it to market in the United States, Time magazine reports. One drug made by Simcere Pharmaceutical is used in China, though it’s unclear if the company is seeking FDA approval. Another, currently used in Japan, is under an expedited FDA review.

Wang, of Rutgers, acknowledged it could take a long time to get the drug his team is studying onto the market, even if it stands up to future testing. He said he would need to find investors and get a pharmaceutical company involved.

For now, he said, “We just want to broadcast [our findings] and tell people this is highly promising. Anyone who is interested in this can either partner with us or work separately to get it to the next stage.”