Antiviral activity against HSV

However, the nucleoside analogue 164 was found to be devoid of activity against HSV-1, HSV-2, VZV and the cytomegalovirus (CMV) in human fibroblast (MRC-5) cells. In this case the decreased conformational flexibility resulting from the introduction of the cyclopropyl group into 164 appeared to be unfavourable for interaction with the enzymes involved (vide supra. Sect. 2.9) [222]. Likewise, the cyclopropylpyrimidine 166c-f and 167, the cyclopropyl-purine nucleosides 168 showed no antiviral activity against HSV-1, HSV-2, HCMV and HIV-1 in cell culture, Eq. (66) [223]. 

Pharmacology Valacyclovir is the hydrochloride salt of L-valyl ester of the antiviral drug acyclovir. Valacyclovir is rapidly converted to acyclovir, which has in vitro and in vivo inhibitory activity against herpes simplex virus types I (HSV-1) and II (HSV-2), and varicella-zoster virus (VZV). In cell culture, acyclovir has the highest antiviral activity against HSV-1, followed by (in decreasing order of potency) HSV-2 and VZV. In vitro, acyclovir triphosphate stops replication of herpes viral DMA in 3 ways 1) Competitive inhibition of viral DMA polymerase 2) incorporation and termination of... 

Dictyota dichotoma and Dictyota linearis [94], The diterpenes isopachydictyolal from Dictyota dichotoma, and 4a-acetyldictyodial, Fig. (8) from Dictyota linearis are new natural products which showed potent antiviral activity against HSV-1 using Vero cells as hosts. 

Certonardosides A-E (23-27), Fig. (9) are sulfated at C-3 of the xylopyranose unit attached to C-26 of the steroidal side chain, while certonardosides F-I (28a, 28b, 29a, 29b), Fig. (10) contain a sulfate group at C-6 (a) of the steroidal aglycone. The isolated compounds were evaluated for their antiviral activity against HIV, HSV, CoxB, EMCV and VSV viruses. Certonardosides A-J were inactive within the range of non cytotoxic concentrations. Only weak antiviral activity against HSV was observed in compounds 29a and 29b and the desulfated analog of 28b. 

Other genera from the Anthemideae tribe also showed a broad spectrum of antiviral activity. Extracts of eight taxa from the genus Echinacea were found to have antiviral activity against HSV-1 in vitro [54], The most potent inhibitors of HSV-1 were Echinacea pallida Bins, Baum Arnason var. sanguinea (Nutt.) Gandhi Thomas 70% ethanol inflorescence extract and Echinacea purpurea (L.) Moench hexane root extract. 

As a result of the intensive search for antiviral substances from medicinal plants, antiviral activity against HSV was found in extracts from Cedrela tubiflora Bertoni, leaves [79], from Prunella vulgaris L., a perennial plant commonly found in China, the British Isles and Europe [80] and from Trichilia glabra L. leaves [81]. Phytochemical studies indicate that these plants contain anionic PS as active constituents which may inhibit HSV by competing for cell receptors as well as by some unknown mechanisms after the virus has penetrated the cells. Furthermore, the in vitro antiviral activity demonstrated by extracts of the medicinal plant Achyrocline flaccida (Weinm.) D.C. on HSV-1 is exerted early during viral replication, essentially during viral adsorption to host... 

Pectic arabinogalactans with unusual P-(l—> 6)-linked D-Galp residues were isolated from leaves of Stevia rebaudiana (Asteraceae family). Their snti-Herpes simplex virus type-1 (HSV-1) activity was evaluated on infected Vero cells treated with different concentrations of polysaccharides and incubated for 72 h. Results showed that the crude polysaccharides exhibited antiviral activity against HSV-1 in-vitro [97]. 

Sulfated galactans Exhibited antiviral activity against HSV-1 and HSV-2 Bostrychia montagnei Duarte et al. (2001)... 

Flavonoid luteoforol isolated from Hypericum connatum (Guttiferae), which is used in southern Brazil in the treatment of lesions in the mouth and often related to acute herpetic gingivo-stomatitis, displayed antiviral activity against HSV-1 DNA viral strains KOS and VR733 (ATCC) (Fritz et al. 2007). Moreover, flavones are inhibitors of HlV-1 proteinase (Brinkworlh et al. 1992). 

The wood essential oil from Cedrus libani widely used as traditional medicine in Lebanon for treatment of different infection diseases are mainly consist of himachalol (22.50%), )3-himachalene (21.90%), and a-himachalene (10.50%) was identified for their in vitro antiviral activities against HSV-1 (Fig. 3.5 Loizzo et al. 2008). 

In addition, the antiviral activity of several other kinds of natural products was also reported. Terpenoids caesahnin B and bonducellpin D from the seeds of traditional Chinese medicinal plant Caesalpinia minax exhibited inhibitory activities on the PI-3 virus in vitro by cytopathogenic effects (CPE) reduction assay (Jiang et al. 2002). Hippomanin A from Phyllanthus urinaria Linnea (Euphorbiaceae), which is a commonly used traditional medicinal plant in oriental countries, exhibited antiviral activity against HSV-2 but not HSV-1 infection (Fig. 3.7 Yang et al. 2007). 

Table 2. C)dotoxicity on MDBK and Vero Cells as well as antiviral activity against HSV-1 and Pl-3 results of the compounds 1-18.

---