Table 3.

Molecular targets for inhibition of norovirus replication.

Target	Function	Inhibitors	Tools
HBGA/capsid Interaction	Receptor binding before cell entry	Dimethyl cyclopenta-α-phenanthren analogues	In silico struct. Biology[56] Crystallography/X-ray[54] Surface plasma resonance technology [56] Mass spectrometry [57] STD NMR [55]
Virus uptake (endocytosis) and uncoating	Cell entry and release of viral RNA	None	Pharmacological inhibitors, neutral red infectious center assay, dominant-negative constructs and siRNA [59], [60].
NS1/2	Intracellular membrane reorganization Determines viral persistence	None	Expression, sub cellular localization and organelle morphology studies[66] Generation of recombinant MNV[50]
NS3	Putative RNA helicase	None	Picornavirus 2C inhibitors [69], [70]
NS4	Intracellular membrane reorganization, antagonizes secretory pathways	None	Picornavirus PI4KIIIb inhibitors [74]
NS5—VPg	Priming for genome polymerization viral protein translation	None	NMR spectroscopy [77]
NS6—protease	Maturation of viral proteins	Substrate-based aldehyde inhibitors [82] Michael-acceptor polypeptide inhibitor [81]	Crystallography/X-ray Biochemical protease assay
NS7—RNA dependent RNA polymerase	Replication of virus genome	2′-C-methylcytidine [98], [99] Favipiravir[100] β-d-N(4)-hydroxycytidine, 2′-F-2′-C-methylcytidine, Ribavirin [99]	Cell culture models Animal models
		5-Nitrocytidine triphosphate [86] 2′-Amino-2′-deoxycytidine-5′-triphosphate (ACT) [87]	Crystallography/X-Ray of RDRP with primer–template
		Suramin, NF023 and NAF2 and PPNDS [88], [89]	In silico struct. Biology Crystallography/X-Ray of RDRP in absence of primer–template Biochemical polymerase assay