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Potent and Selective Inhibition of Human Cytomegalovirus Replication by 1263W94, a Benzimidazole l-Riboside with a Unique Mode of Action
The mechanism of the antiviral effect of l-riboside 1263W94 is thus distinct from those of GCV and of BDCRB, including those resistant to ganciclovir, foscarnet, andBDCRB. Expand
Resistance of Human Cytomegalovirus to Benzimidazole Ribonucleosides Maps to Two Open Reading Frames: UL89 and UL56
The independent isolation of virus that is 20- to 30-fold resistant to TCRB (isolate C4) and the characterization of the virus suggest that the gene products of UL89 and UL56 may be antiviral drug targets. Expand
Inhibition of Human Cytomegalovirus DNA Maturation by a Benzimidazole Ribonucleoside Is Mediated through the UL89 Gene Product
It is shown here that polygenomic concatemeric HCMV DNA does not mature to unit genome length in the presence of BDCRB and that the UL89 open reading frame may encode an endonucleolytic subunit of the putative H CMV terminase. Expand
In Vitro Activities of Benzimidazole d- and l-Ribonucleosides against Herpesviruses
Results demonstrate that the benzimidazole ribonucleosides are active against human CMV and EBV and suggest that they may be useful for the treatment of infections caused by these herpesviruses. Expand
Design, synthesis, and antiviral activity of certain 2,5,6-trihalo-1-(beta-D-ribofuranosyl)benzimidazoles.
It is established that for maximum activity against HCMV with separation from cytotoxicity, ribose is preferred at the 1-position and that Cl or Br is apparently preferred atThe 2-position. Expand
Preclinical and Toxicology Studies of 1263W94, a Potent and Selective Inhibitor of Human Cytomegalovirus Replication
The high level of binding by 1263W94 to human plasma proteins was readily reversible, with less protein binding seen in the monkey, rat, and mouse, and a favorable safety profile was demonstrated. Expand
Inhibition of purine nucleoside phosphorylase by 8-aminoguanosine: selective toxicity for T lymphoblasts.
The guanosine analog 8-aminoguanosine is an effective inhibitor of the purine degradative enzyme purine nucleoside phosphorylase, both in vitro and in intact lymphoid cells. In a human lymphoblastExpand
The synthesis and chemistry of certain anthelmintic benzimidazoles.
In this paper, Leroy Townsend and Dean Wise review the development of some of the synthetic methods that have been critical to the preparation of the benzimidazoles of anthelmintic importance. Expand
Interactions among antiviral drugs acting late in the replication cycle of human cytomegalovirus.
Examination of drug-drug interactions in cell culture assays measuring inhibition of HCMV replication revealed strong synergism for the combination of BDCRB with 1263W94, and for combinations of 12 63W94 with cidofovir (CDV) and foscarnet (PFA), but not with GCV, while antiviral synergy observed between GCV and PFA or CDV serves to validate clinical combination therapies for these drugs. Expand