Official websites use. Share sensitive information only on official, secure websites. Correspondence: manfred. The herpesviral nuclear egress represents an essential step of viral replication efficiency in host cells, as it defines the nucleocytoplasmic release of viral capsids. Due to the size limitation of the nuclear pores, viral nuclear capsids are unable to traverse the nuclear envelope without a destabilization of this natural host-specific barrier. To this end, herpesviruses evolved the regulatory nuclear egress complex NEC , composed of a heterodimer unit of two conserved viral NEC proteins core NEC and a large-size extension of this complex including various viral and cellular NEC-associated proteins multicomponent NEC.
Notably, the NEC harbors the pronounced ability to oligomerize core NEC hexamers and lattices , to multimerize into higher-order complexes, and, ultimately, to closely interact with the migrating nuclear capsids. Moreover, most, if not all, of these NEC proteins comprise regulatory modifications by phosphorylation, so that the responsible kinases, and additional enzymatic activities, are part of the multicomponent NEC.
This sophisticated basis of NEC-specific structural and functional interactions offers a variety of different modes of antiviral interference by pharmacological or nonconventional inhibitors. Since the multifaceted combination of NEC activities represents a highly conserved key regulatory stage of herpesviral replication, it may provide a unique opportunity towards a broad, pan-antiherpesviral mechanism of drug targeting. This review presents an update on chances, challenges, and current achievements in the development of NEC-directed antiherpesviral strategies.
Keywords: human pathogenic herpesviruses, cytomegalovirus HCMV , essential steps of viral replication, viral nucleocytoplasmic capsid egress, nuclear egress complex NEC , core and multicomponent NEC extensions, novel antiviral drug targeting, NEC-directed mode of action, strategies of antiviral drug development. The family of Herpesviridae is characterized by a linear double-stranded DNA genome and a comparatively large size of membrane-enveloped particles comprising — nm [ 1 ].
All herpesviruses share a lifelong persistence within the host with extended latency periods and strongly reduced gene expression, followed by intermittent phases of reactivation causing recurrent symptoms [ 2 , 3 ]. With infection rates spanning approx.
