A new antiviral familiy of compounds targeting of non-essential viral proteins
Advantages
- Novel antiviral strategy have been identified targeting viral non-essential proteins, which are less susceptible to adaptive mutations.
- Based on structural analysis, SARS-CoV-2 ORF9b inhibitors should be active in all coronaviruses, including SARS-CoV and MERS.
- Same approach is being used to target other viral NEP of interest in human or animal pathology, such as the influenza A protein NS-1.
Goal
Licensing and/or co-development.
Patent
EP patent application filed.
Reference
UBTT0503-E
Contact
Fundació Bosch i Gimpera –University of Barcelona:
Rosa Vázquez: rvazquez@fbg.ub.edu
CSIC:
Ana Sanz: ana.sanz@csic.es
A new antiviral familiy of compounds targeting of non-essential viral proteins
Executive summary
A novel antiviral strategy targeting viral non-essential proteins (NEPs), scarcely prone to adaptive mutations, has been built. As a proof of concept, SARS-CoV-2 ORF9b homodimerization inhibitors have been identified that prevents the virus hyperinflammation response.
Introduction
Current antivirals become ineffective over time, largely owed to the accrual of adaptive and escape mutations in target viral proteins. As a novel antiviral strategy, scientists have built a discovery pipeline targeting viral non-essential proteins (NEPs), scarcely prone to adaptive mutations.
Description
As a proof of concept, they have targeted the SARS-CoV-2 NEP (accessory protein) ORF9b and its homodimerization, by applying structure-guided design approaches, chemical synthesis and optimization, experimental protein-protein interaction assays, and in vitro functional assays.
First-in-class inhibitors of ORF9b homodimerization have been identified that counter the pro-inflammatory activities and interferon anergy induced by ORF9b at low micromolar concentrations. The inhibitors have shown to prevent ORF9b mitochondrial localization and activation of inflammasome mediated caspase-1. Moreover, compounds restore IFN-1 responses compromised by viral ORF9b.