In Vitro Activities of Benzimidazole d- and l-Ribonucleosides against Herpesviruses

DOI: 10.1128/AAC.47.7.2186-2192.2003

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FIG. 1.
Structures of benzimidazole ribonucleosides.

TABLE 1.

Effect of benzimidazole nucleosides on alphaherpesvirus replication

↵a Values are expressed as mean ± standard deviation from at least two plaque reduction assays.
↵b Concentration of drug cytotoxic to 50% of HFF cells by neutral red uptake.
↵c Concentrations of drug that inhibit HFF cell growth by 50%.

TABLE 2.

Activity of benzimidazole nucleosides against betaherpesviruses

Virus (cells)	Drug	50% inhibitory concn (μM)
Virus (cells)	Drug	Antiviral activity^a	Cytotoxicity stationary cells^b	Toxicity proliferating cells^b	SI^c
HCMV_AD169 (HFF)	GCV	4.3 ± 0.4	>361	144	>83
	BDCRB	0.4 ± 0.3	170	184 ± 20	425
	1263W94	19.4 ± 18.6	243	58.5 ± 22.1	13
	175X	2.2 ± 0.5	152	143 ± 28	69
HHV-6A_GS (HSB-2)	PFA	13.7 ± 8.3	>166	>166	>12
	BDCRB	>125	>104	>125	—
	1263W94	>125	>133	>133	—
	175X	>125	>125	>126	—
HHV-6A_GS (SupT-1)	CDV	11.7 ± 8	>159	90 ± 18.1	>13
	BDCRB	>125	69 ± 34	70 ± 12	—
	1263W94	>133	>108	>105	—
	175X	>125	>104	>102	—
HHV-6B_Z-29 (CBL)	CDV	1.6 ± 0.6	>159	>159	>100
	BDCRB	>125	>109	>87	—
	1263W94	>106	>98	70 ± 59	—
	175X	95 ± 12	>122	111.8 ± 14	>1.3

↵a Values are the mean ± standard deviation of at least two assays. See Materials and Methods for a description of the assays.
↵b See footnote to Table 1 for description of toxicity assays.
↵c SI, selective index, cytotoxicity in stationary cells/antiviral activity. —, ≤1.

TABLE 3.

Effect of benzimidazole ribonucleosides on laboratory and clinical isolates of HCMV

↵a Values are expressed as the mean ± standard deviation of at least two plaque reduction assays.
↵b NT, not tested.

TABLE 4.

Activity of benzimidazole ribonucleosides on drug-resistant isolates of HCMV

↵a Values are expressed as the mean ± standard deviation of at least two plaque reduction assays.
↵b Control drug for these strains is PFA.
↵c NT, not tested.

TABLE 5.

Effect of benzimidazole nucleosides against various animal CMV strains

↵a Values are expressed as the mean ± standard deviation of at least two plaque reduction assays.
↵b SI, selective index, cytotoxicity in stationary HFF cells/antiviral activity.

TABLE 6.

Effect of benzimidazole nucleosides against the gammaherpesviruses

↵a Values are expressed the mean ± standard deviation of at least two assays.
↵b IFA was performed in EBV assays and FACS was performed in HHV-8 assays.
↵c SI, selective index, cytotoxicity in Daudi or BCBL-1 cells/antiviral activity determined by IFA-FACS.
↵d NT, not tested. —, ≤1.