Promising New Oral Antiviral Drug Targets Resistant COVID-19 Strains

Researchers at Rutgers Health have introduced a new oral antiviral drug candidate designed to effectively combat COVID-19, specifically targeting strains resistant to existing treatments. This innovative drug, named Jun13296, presents several advantages over Paxlovid, the current leading oral treatment for COVID-19.

Unlike Paxlovid, which requires the co-administration of ritonavir, Jun13296 operates independently and focuses on a different viral target. The drug aims to inhibit a structure within the virus known as the papain-like protease (PLpro), which is distinct from the primary protease that Paxlovid targets. Preliminary findings suggest that Jun13296 is significantly more potent than its predecessor, Jun12682, with animal studies demonstrating a remarkable 90% survival rate in mice treated with Jun13296.

Jun Wang, a professor of medicinal chemistry at Rutgers University, noted that this new compound achieves this level of efficacy at only one-third of the dosage required for the earlier version. During tests, the drug not only provided robust protection but also substantially reduced viral loads in the lungs of infected subjects.

One of the critical advancements with Jun13296 is its potential to mitigate the side effects commonly associated with drug interactions. Many at-risk patients, who often manage pre-existing conditions such as hypertension or diabetes, face limitations when prescribed Paxlovid due to these interactions. Jun13296, however, has been designed to avoid these complications, making it a more accessible option for a broader patient demographic.

Laboratory tests indicated that Jun13296 maintains its efficacy against various strains of the virus that have developed resistance to Paxlovid. This aspect is particularly crucial as the virus continues to evolve, necessitating a range of treatment options to ensure preparedness for future surges or outbreaks.

The compound's effectiveness was further validated through collaboration with researchers from Oklahoma State University, where Jun13296 was tested in a controlled environment on infected mice. The results were striking: while untreated mice showed no survival, those receiving the new treatment exhibited a 90% survival rate, in stark contrast to a mere 40% survival for those administered the earlier drug formulation.

In addition to its promising survival rates, Jun13296 has been shown to reduce inflammation significantly and lower viral levels within the lungs. At a dosage of 75 milligrams per kilogram, the new drug demonstrated strong anti-inflammatory properties, whereas the original compound only achieved moderate effects at similar doses.

Another notable advantage of Jun13296 is its lower required dosage compared to Paxlovid. Current studies indicate that Paxlovid requires up to 300 milligrams per kilogram to achieve similar outcomes, thus increasing the risk of side effects. Conversely, Jun13296's efficacy at lower doses minimizes this risk for patients.

Moreover, laboratory tests revealed that Jun13296 does not inhibit major cytochrome P450 enzymes, which are crucial for drug metabolism. This means that patients can take Jun13296 without the need for additional medications like ritonavir, further reducing the likelihood of adverse interactions.

Despite its potential, the journey towards human clinical trials for Jun13296 faces significant financial challenges. Wang estimated that advancing the drug to the necessary stages for investigational new drug applications could require tens of millions of dollars, far beyond what academic institutions typically secure.

The research team is actively seeking partnerships with pharmaceutical companies and nonprofit organizations to facilitate the progression of Jun13296 through preclinical studies and into the FDA approval process.

The development of this new antiviral treatment arrives at a pivotal moment as COVID-19 continues to pose challenges globally, with emerging variants that may evade current therapeutic options. Wang emphasized the need for diverse treatment alternatives to enhance pandemic preparedness. Even if Jun13296 does not reach commercialization immediately, conducting early-stage clinical trials could significantly expedite the approval process in response to future outbreaks.

Furthermore, the methodologies established during this research could be applied to other infectious diseases beyond COVID-19, as the lab specializes in developing antivirals for various respiratory viruses, including influenza and enteroviruses.