Table 1:

Functional characteristics of lead/potent CD4 mimics

Class	Compound	Description	Functional properties	Therapeutic potential	References
Immunoadhesins
	CD4Ig (PRO542)	D1D2 of CD4 fused to Fc portion of Ig	i, ii	Prevention Passive immunization	Jacobsen JM et al, 2000 Jacobsen JM et al, 2004
	eCD4Ig	CD4Ig fused with CoR mimic	i, ii, iii, iv, v	Treatment Antiviral	Davis-Gardner ME et al, 2017 Fellinger CH et al, 2019 Gardner MR et al, 2019
				Cure Kill part of ‘Shock and kill’
Miniproteins
	M48U1	Select CD4 β-hairpin residues transplanted on scyllatoxin scaffold	ii, iv, v	Prevention Topical microbicide	Acharya P et al, 2015
	gp120-S-S-M46U1	M46U1 fused with gp120	i, ii, iii, iv, vi	Treatment Antiviral	Martin G et al, 2011 Dey AK et al, 2012
	gp140-S-S-M46U1	M46U1 fused with gp140	i, ii, iii, iv, vi	Cure Kill part of ‘Shock and kill’
CD4mc
	NBD Series    NBD14110	Analog of NBD556 modified to contain bulky benzodioxole moiety in region I	ii, iv, v		Curelli F et al, 2018
	DMJ-II-121 Analogs    BNM-III-170	Analog of NBD556 modified in region III to an indane core with guanidinium moiety	ii, iv, v, vi	Prevention As part of vaccination	Melillo B et al, 2016; Madani N et al, 2018; Prevost J et al, 2020
				Treatment Antiviral
	YYA-021 Analogs    YIR-821	Analog of NBD556 structurally modified in region III to consist of a mono-cyclohexy with long guanidino extension attached to piperidine core	ii	Cure Kill part of ‘Shock and kill’	Ohashi N et al, 2016
	MCG Series    MCG-IV-210	Novel molecule containing a short amide linker between piperidine core and halogenated aromatic ring	ii, iv, v, vi		Ding S et al, 2019; Grenier MC et al, 2018 Prevost J et al, 2020

ⁱ⁾High avidity binding to gp120

ⁱⁱ⁾Inactivates viral particle

ⁱⁱⁱ⁾Mediates ADCC of infected cells

^iv)Sensitizes infected cells to ADCC

^v)Sensitizes viral particle to neutralisation by nnAbs

^vi)Protects against bystander killing