Two groups of rhinoviruses revealed by a panel of antiviral compounds present sequence divergence and differential pathogenicity.
A variety of chemically different compounds inhibit the replication of several serotypes of rhinoviruses (common-cold viruses). We noticed that one of these antiviral compounds, WIN 51711, had an antiviral spectrum clearly distinctive from a consensus spectrum or other capsid-binding compounds, although all of them were shown to share the same binding site. A systematic evaluation of all known rhinovirus capsid-binding compounds against all serotyped rhinoviruses was therefore initiated. Multivariate analysis of the results revealed the existence of two groups of rhinoviruses, which we will call antiviral groups A and B. The differential sensitivity of members of these groups to antiviral compounds suggests the existence of a dimorphic binding site. The antiviral groups turned out to be a reflection of a divergence of rhinovirus serotypes on a much broader level. Similarities in antiviral spectra were highly correlated with sequence similarities, not only of amino acids lining the antiviral compound-binding-site, but also of amino acids of the whole VP1 protein. Furthermore, analysis of epidemiological data indicated that group B rhinoviruses produced more than twice as many clinical infections per serotype than group A rhinoviruses did. Rhinoviruses belonging to the minor receptor group were without exception all computed to lie in the same region of antiviral group B.
Andries
K
K
Janssen Research Foundation, Beerse, Belgium.
Dewindt
B
B
Snoeks
J
J
Wouters
L
L
Moereels
H
H
Lewi
P J
PJ
Janssen
P A
PA
D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000494:pharmacology*; D001665:Binding Sites; D002213:Capsid / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D017955:Poliovirus / Q000235:genetics; D012229:Rhinovirus / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D012689:Sequence Homology, Nucleic Acid; D014774:Virulence
D000998:Antiviral Agents