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ROME, Feb. 10, 2026 /PRNewswire/ — IRBM, a leader in early drug discovery research, has announced a major scientific breakthrough with the discovery of a novel and potent allosteric inhibitor targeting the Zika virus (ZIKV) protease (NS2B-NS3). The findings, published in Nature Communications (doi: 10.1038/s41467-026-68943-x), demonstrate the molecule’s efficacy in preclinical models and represent a promising new approach to combat ZIKV infections.
Visualization of how IRBM-Z-2 binds to a newly discovered pocket on the Zika virus protease, revealing key interactions that may help block the virus’s activity.
Mosquito-borne ZIKV poses a serious public health threat due to its association with severe neurological complications. With no approved antivirals or vaccines currently available, there is an urgent need for new treatment options.
IRBM scientists identified a small molecule that binds to a previously uncharacterized allosteric site on the NS2B-NS3 protease, a key enzyme required for viral replication. The inhibitor effectively suppressed protease activity in biochemical and cellular assays and demonstrated significant antiviral activity in animal models. It also exhibited a favorable safety and pharmacokinetic profile, supporting its potential for clinical development. Notably, this mechanism may extend to other flaviviruses including dengue, yellow fever, and West Nile, suggesting broader therapeutic potential.
IRBM’s integrated approach, combining high-content phenotypic screening, computational modeling, mechanistic enzymology, iterative medicinal chemistry, and ADME profiling allowed the team to rapidly advance from initial hit identification to preclinical candidate selection.
“This discovery marks an important milestone in antiviral drug development,” said Carlo Toniatti, MD, PhD, Chief Scientific Officer at IRBM. “By leveraging cutting-edge medicinal chemistry and integrated screening technologies, our team has delivered a novel ZIKV protease inhibitor with compelling preclinical activity.”
The achievement, funded by the Region of Lazio, is the result of a collaborative initiative originating from CNCCS, and it opens a promising path toward targeted antiviral therapies that could fill a critical gap in global public health preparedness. It also reinforces the joint commitment of CNCCS and IRBM to tackle rare and neglected diseases with innovative science.
“Innovation in drug discovery never happens alone. At IRBM, we aim to act as a bridge between academic discoveries and the clinic, and the success of this project demonstrates the impact that effective public–private partnerships can have on advancing new therapies,” added Matteo Liguori, CEO and Founder of IRBM.
About IRBM IRBM is a leading research organization specializing in early drug discovery. With decades of expertise and a proven track record of delivering innovative preclinical candidates, IRBM is known for its rigorous, multidisciplinary approach to designing and executing complex experiments for the toughest drug discovery challenges. IRBM advances programs across a wide spectrum of modalities and therapeutic areas, including antivirals, oncology, neuroscience, rare diseases, and beyond.
About CNCCS CNCCS is a public-private consortium between IRBM, CNR, ISS, and the University of La Sapienza, which acts as a lead factory for drug discovery programs, integrating a chemical compound repository with a high-throughput screening (HTS) platform. Its mission is to act as a bridge between academic research and pharmaceutical development, with a particular focus on targeting rare, neglected, and poverty-related diseases.
Website: www.irbm.com
