KEY RESOURCES TABLE

REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
AP33	Owsianka et al., 2005	N/A
AR2A	Law et al., 2008	N/A
AR3A	Law et al., 2008	N/A
AR3B	Law et al., 2008	N/A
AR3C	Law et al., 2008	N/A
AR3D	Law et al., 2008	N/A
AR4A	Giang et al., 2012	N/A
AR5A	Giang et al., 2012	N/A
e20	Mancini et al., 2009	N/A
e137	Perotti et al., 2008	N/A
H77.39	Sabo et al., 2011	N/A
HCV1	Broering et al., 2009	N/A
HEPC3	Bailey et al., 2017	N/A
HEPC13	Bailey et al., 2017	N/A
HEPC43	Bailey et al., 2017	N/A
HEPC74	Bailey et al., 2017	N/A
IGH505	Meunier et al., 2008	N/A
IGH526	Meunier et al., 2008	N/A
e301	Burioni et al., 2002	N/A
e509	Sautto et al., 2012	N/A
H77.16	Sabo et al., 2011	N/A
H77.28	Sabo et al., 2011	N/A
HEPC98	Bailey et al., 2017	N/A
HEPC108	Colbert et al., 2019	N/A
HEPC111	Colbert et al., 2019	N/A
HEPC112	Colbert et al., 2019	N/A
HEPC122	Colbert et al., 2019	N/A
HEPC146	Colbert et al., 2019	N/A
HEPC 151–1	Colbert et al., 2019	N/A
HEPC 151–2	Colbert et al., 2019	N/A
HEPC153	Colbert et al., 2019	N/A
HEPC154	Colbert et al., 2019	N/A
HEPC158	Colbert et al., 2019	N/A
AR1A	Law et al., 2008	N/A
AR1B	Law et al., 2008	N/A
e8	Castelli et al., 2014	N/A
e10	Bugli et al., 2001	N/A
H60	Castelli et al., 2014	N/A
H77.47	Sabo et al., 2011	N/A
HEPC50	Bailey et al., 2017	N/A
HEPC46	Bailey et al., 2017	N/A
S1	Giang et al., 2012	N/A
AB	Giang et al., 2012	N/A
HCVE1-C1	this manuscript	N/A
CD81-LEL fused to immunoglobulin Fc fragment	Gopal et al., 2017	N/A
HRP conjugated secondary Ab	Southern Biotech	Cat# 040–05
Anti CD81 antibody JS-81	BD Biosciences	Cat# 555676
Alexa Fluor 488-conjugated goat anti-human secondary antibody	Jackson ImmunoResearch Laboratories	Cat# 109–545-003
Bacterial and virus strains
E.coli NEB 5-alpha	New England Biolabs	Cat# C987H
Critical commercial assays
Intellicyt high throughput flow cytometer	Sartorius	iQue3
SuperSignal™ West Pico PLUS Chemiluminescent Substrate	ThermoFisher Scientific	Cat# 34580
Renilla-Glo Luciferase assay	Promega	Cat# E2820
Pierce Femto kit	Pierce	Cat# 34095
Imaging System	Bio-Rad	ChemiDoc
Deposited data
HCV partial E2 structure 6MEI	Flyaketal., 2018	PDB 6MEI
HCV partial E1 structure 4UOI	El Omari et al., 2014	PDB 4UOI
HCV partial E1 structure 2KNU	Spadaccini et al., 2010	PDB 2KNU
HCV1 Model structure	Castelli et al., 2017a	N/A
E1E2 mutation library clones, with values for	Mendeley Data	2
Ab binding, infectivity values, Table S3
Experimental models: Cell lines
HEK-293T	ATCC	Cat# CRL-3216
Recombinant DNA
pCMV-dR8.74, lentiviral packaging plasmid	Naldini et al., 1996	N/A
pNL-luc, encoding Renilla luciferase	Connor et al., 1995	N/A
Software and algorithms
Structure Visualization Software	https://www.cgl.ucsf.edu/chimera	UCSF Chimera
GraphPad Prism Graphing software	GraphPad	v 9.0.0
Other
Saponin	VWR	Cat# TCS0019–025G
DMEM	Fisher Scientific	Cat# MT10017CM
Sodium pyruvate	VWR	Cat# 45000–710
L-Alanyl-L-Glutamine	VWR	Cat# 45001–086
HEPES	VWR	Cat# 45000–690
Penicillin-Streptomycin	Fisher Scientific	Cat# 15–140-163
Paraformaldehyde	VWR	Cat# 100496–496
Donor Goat Serum	Atlanta Biologicals	Cat# S13150
DPBS(++)	Cytiva	Cat# SH30264.02
Cellstripper	Corning	Cat# 25–056-CI
Goat Serum	R&D Systems	Cat# S13150
PVDF membrane	VWR	Cat# 28165–512
Precision plus Protein Dual Color Standards	BioRad	Cat# 61–0374