Acyclovir antiviral activity

In this context, it should be noted that the specific antiviral activity of ganciclovir against HSV (which is more potent than that of acyclovir) can be fully explained by the compound being specifically recognized as substrate by the HSV-encoded TK. For CMV, however, which does not encode a virus-specified TK, the activity of ganciclovir depends on the phosphorylation by a vims-encoded protein kinase, which... 

Golankiewicz B, Ostrowski T, Goslinski T, Januszczyk P, Zeidler J, Baranowski D, De Clercq E (2001) Fluorescent tricyclic analogues of acyclovir and ganciclovir. A structure-antiviral activity study, J Med Chem 44 4284 287... 

Catechins and proanthocyanidins have a documented antiviral activity. Catechins from an extract of Cocos nucifera husk fibre exhibited a strong inhibitory activity against acyclovir-resistant herpes simplex virus type 1 (HSV-l-ACVr) [62]. The use of 10 to 20ngml of ECG and EGCG has been reported to cause 50% inhibition of human immunodeficiency virus reverse transcriptase [89], while Kara and Nakayama [90] reported that a patented chewing gum containing tea catechins is claimed to prevent viral infections against influenza and to inhibit dissemination of this virus. 

As it is evident from the chemical strnctnre, acyclovir looks like a nucleoside analog of gnanosine in side chain of which, instead of the traditional cyclic sugar residue a 2-hydrox-yethoxymethyl acyclic side chain is present. Acyclovir possesses antiviral activity with respect to types 1 and 2 of herpes simplex, shingles vims, Epstein-Barr virus, and cytomegalovirns. 

Pharmacology Foscarnet exerts its antiviral activity by a selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases and reverse transcriptases at concentrations that do not affect cellular DNA polymerases. CMV strains resistant to ganciclovir may be sensitive to foscarnet. Acyclovir- or ganciclovir-resistant mutants may be resistant to foscarnet. 

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... 

Colla, L., E. DeClercq, R. Busson, and H. Vanderhaeghe. 1983. Synthesis and antiviral activity of water-soluble esters of acyclovir [9-[(2-hydroxyehtoxy)methyl]guanirvA]Med. Chem26 602-604. 

In the past, various serendipitous discoveries have capitalized on the differential expression of enzymes by host and viral infected cells. For example, the prodrug Acyclovir, used widely for the treatment of herpes simplex and herpes zoster infections, is selectively activated through phosphorylation by viral thymidine kinase to acyclovir monophosphate which is then converted to the triphosphate, which inhibits DNA polymerase, by host cellular enzymes. Similarly several 2, 3 -dideoxynucleoside analogs such as Zidovudine (azidothymidine, AZT) and 2, 3 -didehydro-3 -deoxythymidine (D4T) have potent antiviral activity against human immunodeficiency vims (HIV). These compounds are selectively phosphoiylated intracellularly to the 5 -triphosphate derivatives which inhibit the viral reverse transcriptase. 

Purines in which the sugar moiety is replaced by an abbreviated open-chain surrogate, for example, acyclovir, comprise an important group of antiviral drugs. Antiviral activity is retained when the pyrimidine ring in... 

In particular, acyclovir 1 has become important because of its potent antiherpes activity. Interest in this compound was further enhanced by the finding that, in HS V infected cells, its mechanism of action is due to its specific phosphorylation by the viral-encoded (but not cellular) thymidine kinase to acyclo GMP followed by further phosphorylation by cellular GMP and GDP kinases to the triphosphate, acyclo GTP, which is a selective and potent inhibitor of the HSV DNA polymerase.DHPA (3) and DHPG (2) "" also show significant antiviral activity. These findings have stimulated a widespread interest in. and led to the synthesis of. a large number of purine (and pyrimidine) acyclo nucleosides. " "... 

After oral administration and absorption, valacyclovir is converted to acyclovir, which is the active antiviral component of valacyclovir. The antiviral activity and mechanism of action of valacyclovir is identical to that of acyclovir (Perry and Faulds, 1996). The oral bioavailability of valacyclovir is significantly greater than that of acyclovir. Oral administration of valacyclovir results in plasma acyclovir concentrations comparable to those observed with intravenous acyclovir. 

Antiviral activity has been demonstrated mainly for A. membranaceus, that represents the most studied species, expecially against Coxsackie viruses [234] but also against different kinds of viral infections. "Astragali radix" extracts show protective effects against Japanese Encephalitis Vitus (JEV) infection in mice both by oral and infraperitoneal injection this effect is based on a non-specific mechanism during the early stage of injection, before it shifts to antibody production. A. membranaceus (AM) shows curative effects on the mice infected with Herpes Simplex Virus type-1 (HSV-1) when somministated with acyclovir (ACV) [329]. The anti-HSV activity of suppository and ointment forms of AM combined... 

Chemically stable analogues of acyclovir (26) have been synthesised in an attempt to attain appreciable activity against herpes virus type-1 while allowing their cellular internalisation and bypassing the intracellular activation of acyclovir to its triphosphate derivative required for activity. These compounds are bio-isosteres of acyclovir monophosphate and diphosphate, but are devoid of any appreciable antiviral activity on both HSV-1 and HIV-1. 

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