Researchers at the City University of New York have achieved a significant breakthrough in antiviral development, identifying compounds that could lead to the world's first broad-spectrum antiviral capable of fighting multiple deadly viruses simultaneously. The study, published in Science Advances, demonstrates a novel approach targeting viral envelope glycans that could revolutionize pandemic preparedness.
Novel Target Addresses Critical Gap in Antiviral Arsenal
Unlike bacterial infections, which can be immediately treated with broad-spectrum antibiotics while doctors determine the specific pathogen, viral infections require narrowly targeted antivirals effective against only small sets of related viruses. This limitation leaves populations vulnerable during emerging viral outbreaks.
"Currently, if a new viral outbreak occurs from a new virus (or some old viruses like measles or influenza), we often don't have vaccines or antivirals that are effective against those diseases, so a deadly pandemic can occur," said study author Adam Braunschweig, a nanoscience professor at CUNY's Advanced Science Research Center. "Even if new vaccines and antibodies can be developed, this could take months-to-years and during that time the ill consequences of the disease spread."
The research team addressed this challenge by targeting viral envelope glycans—sugar molecules that are structurally conserved across unrelated viral families and have remained an untapped target for antiviral drug development until now.
Synthetic Compounds Show Broad Antiviral Activity
The researchers screened 57 synthetic carbohydrate receptors (SCRs), small molecules designed to bind to viral glycans. They identified four lead compounds that successfully blocked infection from seven different viruses across five unrelated families, including some of the world's most dangerous pathogens: Ebola, Marburg, Nipah, Hendra, SARS-CoV-1, and SARS-CoV-2.
"The hypothesis was that by binding N-glycans on the surfaces of viral envelopes, we could stop viruses from infecting cells, and in doing so, stop the progression of viral diseases," Braunschweig explained. "This is a groundbreaking hypothesis because of the implications regarding one of the biggest unsolved problems in public health—the desperate need for broad spectrum antivirals."
Promising In Vivo Results Against SARS-CoV-2
In a critical test, one of the lead SCR compounds was used to treat mice infected with SARS-CoV-2. Ninety percent of the mice receiving the SCR survived, compared to none in the control group. Further analysis confirmed that the compounds work by binding to viral envelope glycans—a novel mechanism of action with potential applications not only for infectious diseases but also for cancer and immune disorders.
"Only for SARS-CoV-2 did we test the effectiveness in vivo, in other words in mice. For the other viruses listed, we tested the activity against live virus (except SARS-CoV-1)," Braunschweig noted.
Clinical Development Timeline and Delivery Method
Currently, the antiviral is delivered through the nose because the team focused on respiratory viruses, making delivery to the lungs important for therapeutic efficacy. The next phase of research will focus on advancing the most promising compounds into clinical trials, with Phase I trials anticipated to begin in 2028 after completing preclinical development.
"This is the kind of antiviral tool the world urgently needs," said Braunschweig. "If a new virus emerges tomorrow, we currently have nothing to deploy. These compounds offer the potential to be that first line of defense."
Addressing Pandemic Preparedness
The scientific challenge in developing broad-spectrum antivirals has historically centered on identifying molecular targets involved in viral life cycles that are broadly shared among different viruses. While bacteria present manageable targets, viruses mutate rapidly, causing proteins with similar functions to vary significantly in structure even within viral families.
"These broad-spectrum antivirals, if they make it through clinical trials, could be immediately deployed to mitigate the health consequences, thereby preventing the infected from becoming patients," Braunschweig emphasized. "This would alleviate significantly the burden on public health systems that come under strain when too many infected become patients."
The research was supported by the Army Research Office, National Institutes of Health, New York State Biodefense Commercialization Fund, Air Force Office of Scientific Research, and the COVID-19 High Performance Computing Consortium.
