Rutgers researchers are advancing a potential new COVID-19 treatment, Jun12682, which is effective in animal studies and compatible with other medications, unlike the current leading treatment, Paxlovid.
Researchers at Rutgers believe they are among the lead in developing an oral COVID-19 treatment that could supplement or replace Paxlovid, an antiviral drug that aids in preventing hospitalizations among high-risk patients.
Their report, published in the journal Science, shows that an alternative medication, a viral papain-like protease inhibitor, inhibits disease progression in animals, a necessary step before human drug trials.
“COVID-19 remains the nation’s third leading cause of death, so there’s already a massive need for additional treatment options,” said Jun Wang, senior author of the study and an associate professor who runs a research lab at Rutgers’ Ernest Mario School of Pharmacy. “That need will grow more urgent when, inevitably, COVID-19 mutates in ways that prevent Paxlovid from working.”
Development of a Novel Drug
The Rutgers team hoped to make a drug that interfered with viral papain-like protease (PLpro), a protein that performs important functions in all known strains of COVID-19.
Creating such a drug required detailed information about PLpro’s structure, which Wang’s team got from the Arnold Lab at Rutgers’ Center for Advanced Biotechnology and Medicine (CABM).
Precise knowledge of PLpro’s structure enabled Wang’s team to design and synthesize 85 drug candidates that would bond to – and interfere with — this vital protein.
“The PLpro crystal structures showed an unexpected arrangement of how the drug candidate molecules bind to its protein target, leading to innovative design ideas implemented by professor Wang’s medicinal chemistry team,” said Eddy Arnold, who is a professor at CABM and the Rutgers Department of Chemistry and Chemical Biology.
Laboratory testing established that the most effective of those drug candidates, a compound dubbed Jun12682, inhibited several strains of the SARS-CoV-2 virus, including strains that resist treatment with Paxlovid.
Subsequent testing on SARS-CoV-2-infected mice by the Deng lab at Oklahoma State University showed that oral treatment with Jun12682 reduced viral lung loads and lesions while improving survival rates.
“Our treatment was about as effective in mice as Paxlovid was in its initial animal tests,” said Wang, who added the experimental drug appears to have at least one major advantage over the older drug.
“Paxlovid interferes with many prescription medications, and most people who face the highest risk of severe COVID-19 take other prescription medicines, so it’s a real problem,” Wang said. “We tested our candidate Jun12682 against major drug-metabolizing enzymes and saw no evidence that it would interfere with other medications.”
Rutgers has submitted patent applications for Jun12682, along with the other 84 drug candidates, and is looking for partners to help move the drug candidate forward through further stages of testing and development.
Reference: “Design of a SARS-CoV-2 papain-like protease inhibitor with antiviral efficacy in a mouse model” by Bin Tan, Xiaoming Zhang, Ahmadullah Ansari, Prakash Jadhav, Haozhou Tan, Kan Li, Ashima Chopra, Alexandra Ford, Xiang Chi, Francesc Xavier Ruiz, Eddy Arnold, Xufang Deng and Jun Wang, 28 March 2024, Science.
DOI: 10.1126/science.adm9724

News
Small antibodies provide broad protection against SARS coronaviruses
Scientists have discovered a unique class of small antibodies that are strongly protective against a wide range of SARS coronaviruses, including SARS-CoV-1 and numerous early and recent SARS-CoV-2 variants. The unique antibodies target an [...]
Controlling This One Molecule Could Halt Alzheimer’s in Its Tracks
New research identifies the immune molecule STING as a driver of brain damage in Alzheimer’s. A new approach to Alzheimer’s disease has led to an exciting discovery that could help stop the devastating cognitive decline [...]
Cyborg tadpoles are helping us learn how brain development starts
How does our brain, which is capable of generating complex thoughts, actions and even self-reflection, grow out of essentially nothing? An experiment in tadpoles, in which an electronic implant was incorporated into a precursor [...]
Prime Editing: The Next Frontier in Genetic Medicine
By Dr. Chinta SidharthanReviewed by Benedette Cuffari, M.Sc. Discover how prime editing is redefining the future of medicine by offering highly precise, safe, and versatile DNA corrections, bringing hope for more effective treatments for genetic diseases [...]
Can scientists predict life longevity from a drop of blood?
Discover how a new epigenetic clock measures how fast you are really aging from just a drop of blood or saliva. A recent study published in the journal Nature Aging constructed an intrinsic capacity (IC) clock [...]
What is different about the NB.1.8.1 Covid variant?
For many of us, Covid-19 feels like a chapter we’ve closed – along with the days of PCR tests, mask mandates and daily case updates. But while life may feel back to normal, the [...]
Scientists discover single cell creatures can learn new behaviours
It was previously thought that learning behaviours only applied to animals with complex brain and nervous systems, but a new study has proven that this may also occur in individual cells. As a result, this new evidence may change how [...]
Virus which ’causes multiple organ failure’ found at popular Spanish holiday destination
British tourists planning trips to Spain have been warned after a deadly virus that can cause multiple organ failure has been detected in the country. The Foreign Office issued the alert on its dedicated website Travel [...]
Urgent health warning as dangerous new Covid virus from China triggers US outbreak
A dangerous new Covid variant from China is surging in California, health officials warn. The California Department of Public Health warned this week the highly contagious NB.1.8.1 strain has been detected in the state, making it the [...]
How the evolution of a single gene allowed the plague to adapt, prolonging the pandemics
Scientists have documented the way a single gene in the bacterium that causes bubonic plague, Yersinia pestis, allowed it to survive hundreds of years by adjusting its virulence and the length of time it [...]
Inhalable Nanovaccines: The Future of Needle-Free Immunization
The COVID-19 pandemic highlighted the need for adaptable and scalable vaccine technologies. While mRNA vaccines have improved disease prevention, most are delivered by intramuscular injection, which may not effectively prevent infections that begin at [...]
‘Stealthy’ lipid nanoparticles give mRNA vaccines a makeover
A new material developed at Cornell University could significantly improve the delivery and effectiveness of mRNA vaccines by replacing a commonly used ingredient that may trigger unwanted immune responses in some people. Thanks to [...]
You could be inhaling nearly 70,000 plastic particles annually, what it means for your health
Invisible plastics in the air are infiltrating our bodies and cities. Scientists reveal the urgent health dangers and outline bold solutions for a cleaner, safer future. In a recent review article published in the [...]
Experts explain how H5 avian influenza adapts to infect more animals
A new global review reveals how rapidly evolving H5 bird flu viruses are reaching new species, including dairy cattle, and stresses the urgent need for coordinated action to prevent the next pandemic. Since its [...]
3D-printed device enables precise modeling of complex human tissues in the lab
A new, easily adopted, 3D-printed device will enable scientists to create models of human tissue with even greater control and complexity. An interdisciplinary group of researchers at the University of Washington and UW Medicine [...]
Ancient DNA sheds light on evolution of relapsing fever bacteria
Researchers at the Francis Crick Institute and UCL have analyzed ancient DNA from Borrelia recurrentis, a type of bacteria that causes relapsing fever, pinpointing when it evolved to spread through lice rather than ticks, and [...]