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