Picornavirinae, Picornaviridae, Enterovirus Order Family Genus
SpeciesHRV-A (75 types)
HRV-B (25 types)
HRV-C (48 types)
Genotypes share>87% VP1 proteinidentity (136x)
Species share>70% VP1 proteinidentity
HRV-C RNA in infected sinus mucosa
Bochkov Y et al Nature Medicine (Apr10, 2011)
The HRV-A and HRV-B use ICAM-1 (88x) or LDLR (11x)
receptors
HRV-14 x ICAM-1
High resolution structures and footprint maps exist for both types of receptor interactions
A16
1ay
mB
14 4
rhv
C15
mod
el5x
5x
5x For all HRV-C every VP1 lacks
35 aa relative to HRV-B21 aa relative to HRV-AAll mass loss is at 5x
C15 model predicts the new "5x well" would be perfect fit for (e.g.) sialic acid
HRV-B14 (4hrv) HRV-C15 (model)
Chimera renderings: Shorter 5-fold vp1 loops make 5-fold well
HRV-A16 (1ncr) HRV-C15 (Model #3)
5-fold close-up (radial depth-cue)
HRV-A16 (1ncr) HRV-C15 (Model #3)
Slice at 5-fold5-fold 5-fold
vp1 vp1 vp1 vp1
HRV-A16 (1ncr) HRV-C15 (Model #3)
Antiviral drugs like pleconaril bind within a VP1 pocket
and prevent protein rearrangements during uncoating
3-{3,5-dimethyl-4-[3-(3-methylisoxazol-5-yl)propoxy]phenyl}-5-(trifluoromethyl)-1,2,4-oxadiazole
CHEMBL 29069
C15 model
C15 drug binding pocket fits A16 almost
perfectly
A16 1ncr
C15 model
B14 1ncq
A16B14C15
AreHRV-CType 2
drug group?
pleconaril