Table 2.

Summary of MERS-CoV S protein-targeting peptides and other therapeutic agents^a.

Therapeutic name	Target region	Mechanism of inhibition of virus infection	In vivo protection	Crystal structures available	Ref.
Anti-DPP4 agents targeting RBD
Anti-DPP4 mAbs  2F9, 1F7, YS110	RBD-binding region in DPP4	Blocks RBD binding to hDPP4, thus preventing virus entry into target cells and inhibiting MERS-CoV infection	Not reported	N/A	[82]
DPP4 antagonist	RBD-binding region in DPP4	Competes with RBD binding to hDPP4, inhibiting MERS-CoV infection	Not reported	N/A	[83]
Peptides targeting S2-HR1
HR2L  HR2P  HR2P-M1  HR2P-M2	S2-HR1	Blocks 6-HB formation; inhibits MERS-CoV S-mediated cell-cell fusion at lower micromolar; inhibits pseudotyped and live MERS-CoV infection	HR2P-M2 protects Ad5/hDPP4-transduced mice and hDPP4-Tg mice from challenge of MERS-CoV (EMC2012) with or without mutations	Yes, HR1/HR2-6-HB complex	[59,84,85]
P1	S2-HR1	Inhibits pseudotyped MERS-CoV infection	Not reported	Yes, HR1/HR2-6-HB complex	[50]
Others affecting the function of MERS-CoV S protein
Cathepsin inhibitors	Cathepsin	Blocks MERS-CoV S-mediated cell entry and virus-cell membrane fusion	Not reported	N/A	[66,86]
TMPRSS2 inhibitors	TMPRSS2	Blocks MERS-CoV S-mediated cell entry and virus-cell membrane fusion	Not reported	N/A	[65]
Furin inhibitors	Furin	Blocks MERS-CoV S-mediated cell entry and virus infection	Not reported	N/A	[68]
siRNA	Furin	Silences furin activity, thus decreasing MERS-CoV S-mediated cell entry	Not reported	N/A	[68]
IFITM proteins	S?	Blocks MERS-CoV S-mediated cell entry potentially through mechanisms other than endosomal cholesterol accumulation	Not reported	N/A	[87]

^aN/A: not applicable. DPP4: dipeptidyl peptidase 4; hDPP4-Tg mice: human DPP4-transgenic mice; 6-HB: 6-helix bundle; HR1 and HR2: heptad repeat region 1 and 2; MERS-CoV: Middle East respiratory syndrome coronavirus; RBD: receptor-binding domain; S: spike protein.