Understanding human rhinovirus infections in terms of QSAR.
The human rhinoviruses (HRVs) are the single most important cause of common colds. The widespread nature of this affliction, the economic consequences, and the well-known impracticality of vaccine development due to the large number of HRV serotypes (>100) have justified the search for chemotherapeutic agents. The interest in the application of quantitative structure-activity relationships has steadily increased in recent decades and we hope it may be useful in the search for anti-HRV agents. In the present paper, we have discussed the inhibition of various six compound series against HRV-1A, -1B, -2, -9, -14, -21, -22, -25, -64, and -89 by the formulation of a total number of 14 QSAR. Hydrophobicity is found to be one of the most important determinants of activity. Parabolic correlation with the hydrophobic parameter (Eq. ) is an encouraging example, where the optimal hydrophobicity is well defined. We believe that this may be the predictive model to narrow the synthetic challenges in order to yield very specific HRV-2 inhibitors. On the basis of this model, we have predicted eleven compounds (I-1 to I-11) that may be the next synthetic target. The proposed molecules (I-1 to I-11) also fulfill the conditions of Lipinski's "rule of five".
Verma
Rajeshwar P
RP
Department of Chemistry, Pomona College, 645 North College Avenue, Claremont, CA 91711, USA. rverma@pomona.edu
Hansch
Corwin
C
D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D019295:Computational Biology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015394:Molecular Structure; D010850:Picornaviridae Infections / Q000821:virology*; D021281:Quantitative Structure-Activity Relationship; D012229:Rhinovirus / Q000187:drug effects*; D013223:Statistics as Topic
D000998:Antiviral Agents