Methods for Screening and Identifying Agents That Inhibit or Modulate the Nuclear Egress Complex of Herpesviruses

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This patent discloses novel methods and tools for identifying and developing agents (such as small molecules, peptides, or antibodies) that inhibit or modulate the nuclear egress complex (NEC) of herpesviruses, including human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), and varicella zoster virus (VZV). The invention is based on high-resolution crystal structures of NEC protein complexes, which enable the rational design and screening of compounds that block key protein-protein interactions essential for viral replication and maturation. By targeting highly conserved mechanisms and structural features of the NEC, this approach opens pathways for the development of new broad-spectrum antiviral therapies.

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• Development of new antiviral drugs for treating infections caused by herpesviruses (e.g., HCMV, EBV, VZV) in immunocompromised patients, transplant recipients, and neonates.
• High-throughput screening for small molecules or biologics that disrupt NEC protein interactions, enabling pharmaceutical companies to rapidly identify antiviral leads.
• Basic research tools for studying the molecular mechanisms of herpesvirus replication and nuclear egress.
• Diagnostic assays to detect inhibitors or assess the function of NEC-related proteins in clinical or laboratory settings.
• Design of targeted therapies—such as peptide- or antibody-based inhibitors—against conserved NEC structures for pan-herpesvirus activity.

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• Potential for development of broad-spectrum antiviral agents effective against multiple herpesvirus species due to targeting of highly conserved NEC structures.
• Enables rational drug design by providing detailed structural information on viral NEC proteins, allowing for structure-based screening and optimization of drug candidates.
• Improves specificity and efficiency in identifying antiviral compounds compared to traditional, non-targeted screening methods.
• Facilitates discovery of lower-toxicity therapies by identifying agents that act specifically on viral processes rather than host cell mechanisms.
• May lead to innovative prophylactic (preventative) treatments as well as therapies for active or chronic herpesvirus infections, improving outcomes in vulnerable patient populations.

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Patent Abstract

The present invention generally provides for a novel NEC-targeted strategy for the development of antiherpesviral drugs as well as for a novel antiviral strategy targeting the viral-cellular nuclear egress complex (NEC) for a small molecule-based therapy or prophylaxis to control infections with human cytomegalovirus or other pathogenic viruses of the group of the Herpesviridae. Methods for screening agents / compounds /small molecules modulating/ inhibiting the nuclear egress complex of Herpesviridae are provided as well. Specifically novel drug targets of the viral nuclear egress complex of viruses of the Herpesviridae are provided.