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Invention Portfolio Summary:
Enterovirus D68 (EV-D68) is an RNA virus in the Picornaviridae family, is a re-emerging pediatric pathogen associated with recurrent outbreaks, can cause severe respiratory disease, and has also been linked to acute flaccid myelitis (AFM), whose incidence has risen steadily over the past decade. There are no approved antivirals or vaccines, representing a major unmet medical need. Reported inhibitors, including those targeting the viral 2C protein, lack sufficient potency, selectivity, and pharmacokinetic profiles for clinical development.
Rutgers researchers have developed multiple complementary antiviral approaches targeting EV-D68 that together advance both therapeutic discovery and translational development. These innovations include:
Method and Compositions:
• Structure-guided VP1 capsid inhibitors: Novel small-molecule inhibitors targeting the hydrophobic canyon of the EV-D68 VP1 capsid protein, a critical site for viral attachment and uncoating. These inhibitors were designed using high-resolution cryo-EM structures and demonstrate nanomolar antiviral potency across multiple EV-D68 strains, with in vivo efficacy demonstrated in a neonatal mouse model of EV-D68–associated paralytic myelitis.
• First-in-class 2C ATPase inhibitors: Small-molecule inhibitors targeting the essential and highly conserved EV-D68 2C ATPase, a viral motor protein required for RNA replication, membrane remodeling, and viral assembly. These compounds exhibit potent antiviral activity and provide a high genetic barrier to resistance.
• Complementary dual-mechanism antiviral strategy: Targeting both viral entry/uncoating (VP1) and replication (2C ATPase) enables a resistance-aware approach and supports the development of standalone or combination antiviral regimens.
Market Applications:
- Antiviral drug development for Enterovirus D68 and acute flaccid myelitis
- Combination antiviral regimens targeting both capsid (VP1) and replication (2C ATPase) mechanisms
- Broad-spectrum enterovirus therapeutic development based on 2C inhibition
- Pediatric infectious disease therapeutics addressing unmet medical needs during EV-D68 outbreaks
Advantages:
Introduces first-in-class, structure-guided small-molecule EV-D68 antivirals targeting both the VP1 capsid protein and the essential 2C ATPase, providing complementary mechanisms of action.
- Nanomolar antiviral potency across multiple EV-D68 strains (in vivo efficacy validated in a neonatal mouse model).
- High genetic barrier to resistance and supports combination antiviral therapy.
- Broad-spectrum antiviral potential through conserved 2C inhibition enables expansion toward other enterovirus indications, strengthening commercial impact.
Publications:
- Tan B, Liu C, Li K, et al. Structure-Based Lead Optimization of Enterovirus D68 2A Protease Inhibitors. J Med Chem. 2023;66(21):14544-14563. doi:10.1021/acs.jmedchem.3c00995
- Li K, Demssie HA, Wang J. Design of a Fluorescence Polarization Probe for Enterovirus 2C Proteins. J Med Chem. 2025;68(13):14041-14053. doi:10.1021/acs.jmedchem.5c01219
Intellectual Property & Development Status: PCT patent application filed, patent pending. Available for licensing and/or research collaboration. For any business development and other collaborative partnerships, contact: marketingbd@research.rutgers.edu
