New research out of the University of Texas Medical Branch reveals findings that drug candidate NITD-688 utilized a unique way to stop dengue, a potentially life-threatening infection spread by mosquitos.
Dengue, caused by the dengue virus, presents a significant public health challenge with limited effective treatments. Primarily transmitted to humans through the bite of infected mosquitoes, the virus can cause diseases ranging from mild flu-like illness to life-threatening dengue hemorrhagic fever and dengue shock syndrome.
Dengue is now endemic in more than 120 countries in Africa, the Americas, the Eastern Mediterranean, Southeast Asia and the Western Pacific. Nearly half of the world's population is at risk of dengue with an estimated 100 million to 400 million infections and 40, 000 deaths occurring each year.
Vaccine and vector control, the only current measures used to combat dengue, face significant limitations. Despite decades of efforts, therapeutics, including antibody and small molecule drugs, are not yet clinically available, leaving dengue management reliant on supportive care, which is usually inefficient.
A promising direct-acting antiviral candidate, NITD-688 (developed by Novartis), was able to stop a dengue infection in preclinical studies. It is now being tested in Phase 2 clinical trials to treat dengue patients.
The UTMB study reveals that NITD-688 specifically disrupts the critical interactions between the viral proteins (called “NS3” and “NS4B”) that are part of the “factory” where the dengue virus replicates itself. UTMB research suggests that NITD-688 can directly destroy the protein’s viral replication factory and halt dengue infection.
“Our study advances our understanding of NITD-688’s mechanism of action, offering valuable insights for developing novel flavivirus inhibitors and guiding future clinical interventions against dengue,” said lead researcher Dr. Xuping Xie, associate professor in the Department of Microbiology and Immunology and scientific director at the Sealy Institute for Drug Discovery at UTMB.
The research was supported by the UTMB-Novartis Alliance for Pandemic Preparedness, one of the NIH-funded Antiviral Drug Discovery Centers. UNAPP is co-led by Xie and Dr. Vineet D. Menachery (formerly at UTMB, now at Emory University).
Beyond addressing urgent medical needs like dengue, UNAPP has built a robust pipeline for discovering and developing antiviral drugs targeting high-priority pathogens, including coronaviruses and henipaviruses.
“This work exemplifies a successful academic-industry collaboration between UTMB and Novartis,” Xie said. “Given the ongoing outbreaks of dengue, H5N1 bird flu, measles virus and many others, continued support for such partnerships is essential for the rapid development of therapeutics to respond to current and future viral threats to public health and economy.”
The report was published in PNAS, the peer-reviewed journal of the National Academy of Sciences.