Table 1. Key findings and future implications of the new HCV E2 envelope glycoprotein core structure described by Kong et al.⁸.

Experiment objective	Tools	Technique employed	Main results	Functional relevance Future implications
Structural characterization of E2	E2c AR3C FAb	X-Ray crystallography	General globular shape despite irregular secondary structure, Central β sandwich bordered by two layers (front and back) comprising loops, short helices and β sheets	Understanding of : HCV morphology HCV/CD81 interactions HCV fusion process
	E2ΔTM AR3C FAb	Negative-stain EM	Confirmation of E2 globular structure, Remapping of regions absent in the E2c: N-terminal region next to the β sandwich Region 454-491 at the opposite face of the β sandwich C-terminal region behind back layer	HCV/host factors interaction research, Entry inhibitor development, Immunopreventive strategies, Vaccine design
Determination of CD81 receptor binding site	E1E2 heterodimer	Site-directed mutagenesis ELISA	Interaction of CD81 with residues of the front layer and the CD81 binding loop of E2
	d E2ΔTM Dimer of CD81 LEL AR2A FAb	Negative-stain EM	A dimer of CD81 and AR3C interacts with the same site on E2

E2c: aa 412-645, truncations at N- and C- termini, aa 460-485 substituted by a linker, removal of N448 and N576 E2ΔTM: aa 384-717; d E2ΔTM: Deglycosylated E2ΔTM; LEL: large external loop; EM: electron microscopy; ELISA: enzyme-linked immunosorbent assay