IRBM, a leader in early drug discovery research, recently announced a major scientific breakthrough with the discovery of a new and potent allosteric inhibitor targeting the Zika virus (ZIKV) protease (NS2B-NS3).
The results, published in Nature Communications, 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 currently available approved antivirals or vaccines, there is an urgent need for new treatment options.
IRBM scientists have identified a small molecule that binds to a previously uncharacterised 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 favourable 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 a broader therapeutic potential.
IRBM’s integrated approach, combining high-content phenotypic screening, computational modelling, mechanistic enzymology, iterative medicinal chemistry, and ADME profiling, enabled the team to rapidly advance from initial hit identification to preclinical candidate selection.
This achievement, funded by the Lazio Region, is the result of a collaborative initiative originating from the CNCCS and opens a promising path for targeted antiviral therapies that can fill a critical gap in global public health preparedness. It also reinforces the joint commitment of the CNCCS and IRBM to combating rare and neglected diseases with innovative science.
