Phenylboronic-acid-based carbohydrate binders as antiviral therapeutics: monophenylboronic acids.
BACKGROUND
The development of carbohydrate-binding agents as novel therapeutics for the inhibition of highly glycosylated enveloped viruses has generated much attention in recent literature. Possessing a potential dual mode of action by inhibiting virus entry and exposing the virion to neutralization by the host immune system upon the deletion of envelope glycans under drug pressure, these substances might provide a new direction in antiviral treatment. Phenylboronic acids are widely known to bind the cis-diol functionality of carbohydrate structures, thereby identifying themselves as potential lead structures. To date, few details have been disclosed of the structure-activity relationship of these substances in correlation to their antiviral activity.


METHODS
In this study, a compound library of a diverse range of ortho-, meta- and para- ring-substituted monophenylboronic acids and glutamine phenylboronic acid analogues was prepared, characterized and evaluated to probe antiviral activity versus a broad range of (enveloped) viruses.


RESULTS
The compounds described herein lack antiviral activity. They also did not show measurable binding to HIV type-1 (HIV-1) gp120, using surface plasmon resonance technology. However, of note is the general lack of toxicity, which suggests that further investigation of the compounds as potential therapeutics is needed.


CONCLUSIONS
The monophenylboronic acids tested exhibited no antiviral activity as potential carbohydrate binders versus a broad range of enveloped and non-enveloped viruses. The compounds tested did not bind HIV-1 gp120, possibly because of their small size and lack of multivalency.
Trippier
Paul C
PC
Welsh School of Pharmacy, Cardiff University, Cardiff, UK.
McGuigan
Christopher
C
Balzarini
Jan
J
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001897:Boronic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D024882:Drug Resistance, Viral; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008826:Microbial Sensitivity Tests; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D053586:Virus Internalization / Q000187:drug effects; D014780:Viruses / Q000187:drug effects* / Q000378:metabolism
D000998:Antiviral Agents; D001897:Boronic Acids; D015699:HIV Envelope Protein gp120; D011134:Polysaccharides; C010686:benzeneboronic acid