53 Interfering with HCV cell entry offers several targets at different steps of viral entry: blocking virus target cell interaction during attachment, interfering with postbinding events such as CD81-CLDN1 assoriations or viral fusion.
Through a subtle binding interplay between Arb, lipids, viral and cellular proteins, Arb might efficiently block HCV entry and membrane fusion interacting with the main actors of the early steps of viral entry.
Although the early steps of viral entry have yet to be elucidated, several cell-surface expressed molecules have been proposed as entry factors for HCV (reviewed in [9]).
Several steps of the entry process can be targeted by drugs.
Viral infection involves several major steps of viral entry, replication, assembly and release (Dimmock et al., 2007).
Many viral genomes encode small, integral membrane proteins that form homo-oligomeric channels in membrane, and they transport protons, cations, and other molecules across the membrane barrier to aid various steps of viral entry and maturation.
CLDN1 does not directly interact with HCV glycoproteins and contributes to the post-binding steps of HCV entry by interacting with CD81 (Evans et al., 2007; Harris et al., 2010; Lindenbach and Rice, 2013).
Furthermore, we have taken advantage of the flexibility of pseudotyped particles to investigate the molecular mechanisms underlying initial steps of virus entry following cell attachment.
This finding indicates that the early steps of HCV entry into its target cells involve tight control of CD81 accessibility to the viral particle.
Our findings pave the way towards the design of new drugs exhibiting Arb-like interfacial membrane binding properties to inhibit early steps of virus entry, i.e., attractive targets to combat viral infection.
