Viral assembly protein complexes

Viral assembly protein complexes are essential multi-protein machineries that coordinate the final stages of the viral life cycle, specifically the packaging of the viral genome into a protective protein shell known as a capsid (1.1.1, 1.1.2). These complexes rely on highly specific protein-protein and protein-nucleic acid interactions to assemble hundreds or thousands of individual subunits into a functional, infectious virion (1.1.1, 1.3.1). Because these structural proteins are unique to the virus and lack human homologs, they serve as attractive targets for direct-acting antivirals (1.3.1, 1.3.4). Therapeutic strategies include the use of capsid assembly modulators (CpAMs) that either block subunit association or induce the formation of non-infectious, aberrant particles (1.3.1, 1.3.2). Notable drugs targeting these complexes include lenacapavir for HIV-1 and various core protein allosteric modulators for Hepatitis B virus (1.3.1, 1.3.2). Additionally, novel inhibitors targeting the membrane (M) protein of coronaviruses have recently been identified to block the assembly of SARS-CoV-2 (1.2.1, 1.2.3). While these targets offer high specificity, the primary challenge in their clinical application is the rapid emergence of drug-resistant mutations within the viral structural genes (1.2.1, 1.3.1).

Other names

Viral assembly machineryCapsid assembly complexesNucleocapsid assemblyVirion assembly complexesViral structural protein complexes

Inhibition of capsid assembly, stabilization of aberrant viral particles, disruption of protein-protein interactions, and inhibition of viral maturation.