Anti-HCMV

Nguyen-Ba, P, Lee, N., Mitchell, H., Chan, L., and Qnimpere, M., Design and synthesis of a novel class of nucleotide analogs with anti-HCMV activity, Bioorg. Med. Chem. Lett., 8, 3555, 1998. 

The D-erythrofuranosyl benzimidazole 4, various related 2-substituted analogues and some compounds additionally halogenated at C-4 have been prepared by base-sugar coupling. The enantiomer of 4 was also made, since the analogous L-ribofuranosyl compound has anti-HCMV activity. Some of the novel compounds also proved effective against HCMV. ... 

The naturally occurring oxetanocin A (18) and synthetic oxetanocin G (19) represent a novel class of nucleosides possessing antiviral propmies. Modification of die unique oxetanosyl-lV-glycoside structural feature of 18 and 19 into the carbocyclic nucleoside framework led to the synthesis of 20 and 21 as racemates and enantiomers, which have shown activity against herpesviruses and HIV.22b,c,24,25 in view of the potent and selective anti-HCMV properties of the l -enantiomer of 21, the synthesis of the R sto eoisomer 22 was undertaken and accomplished. 

Azetidine 25 has shown promising anti-human cytomegalovirus (HCMV) activity. Human cytomegalovirus is a ubiquitous member of the herpes virus family. The EGso value obtained for this compound has been found to be similar to that of the standard reference compound ganciclovir and slightly better than that of cidofovir... 

The activities of soyasaponin I (26) and II (26b) were studied in vitro against HSV-1 [153]. Soyasaponin II was more potent than soyasaponin I as shown by the reduction of HSV-1 production. Soyasaponin II also inhibited the replication of HCMV, HIV-1 and influenza virus. The action was not due to inhibition of virus penetration and protein synthesis, but might involve a virucidal effect. Additive antiviral effects were observed when soyasaponin II (200 pM and lOOOpM) was evaluated in combination with acyclovir (1,5, and 25 pM) for anti-HSV-1 activity... 

Lewis A. F, Revankar G. R, Fermanwald S. M, Huffman J. H, Rando R. F. Thiazo-lo[4,5-d]pyrimidines. Part I. synthesis and anti-human cytomegalovirus (HCMV) activity in vitro of certain alkyl derivatives, J. Heterocyclic Chem. 1995. p. 547 - 556. DOI 10.1002/jhet.5570320230... 

Besides the role of retinoids in host immune defenses to viral infections (see [6] for review), retinoids may also affect virus replication. Angulo et al. [44] characterized three RA response elements in the promoter region of human cytomegalovirus (hCMV) and demonstrated the necessity for RAR and RXR in the viral promoter s positive response to RA. In contrast, the replication of herpes simplex virus-1 (HSV-1) in cultured Vero cells was inhibited by isomers of RA, but not retinol inhibition occurred without evident induction of IFN-a or IFN-p gene expression [45]. RA also protected HL-60 and WISH cells from infection with vesicular stomatitis virus (VSV) [46] however, in this case RA significantly increased the ability of IFN-a to decrease virus replication. These apparently contrasting effects of RA on hCMV as compared to HSV-1 or VSV replication further illustrate the potential for retinoids to act either positively or negatively in host resistance to viral infection and anti-viral immunity. Retinoid-IFN interactions are further discussed later in this chapter. 

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