Drugs online research references
J Biol Chem. 1995 Mar 31;270(13):7055-60.
Purification and photoaffinity labeling of herpes simplex virus type-1 thymidine kinase.
Rechtin TM, Black ME, Mao F, Lewis ML, Drake RR.
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
The molecular basis for the treatment of human herpesviruses with nucleoside drugs is the phosphorylation of these drugs by the viral-encoded thymidine kinases. In order to better understand the structural and enzymatic mechanisms by which herpesviral thymidine kinases recognize their substrates, photoaffinity labeling with [alpha-32P]5-azido-2'-deoxyuridine-5'-monophosphate and [ gamma-32P]8-azidoadenosine-5'-triphosphate was used to characterize the thymidine, thymidylate, and ATP active sites of the herpes simplex virus-1 (HSV-1) thymidine kinase. For this study, HSV-1 thymidine kinase and a site-specific mutant enzyme (C336Y, known to confer acyclovir resistance) were expressed in bacteria and purified by a rapid, two-step protocol. The specificity of photoaffinity labeling of these HSV-1 thymidine kinases was demonstrated by the ability of site-directed substrates such as thymidine, thymidylate, acyclovir, 5-bromovinyl-2'-deoxyuridine, and ATP to inhibit photoinsertion. Differences in inhibition patterns of photoaffinity labeling correlated with kinetic differences between the wild-type and C336Y HSV-1 thymidine kinases. Cumulative results suggest that the acyclovir-resistant cysteine 336 mutation primarily affects the ATP binding site; yet it also leads to alteration in the binding affinity of nucleoside drugs in the thymidine site. In this study, azidonucleotide photoaffinity analogs are shown to be effective tools for studying the active-site environment of HSV-1 thymidine kinase and related site-specific mutants.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7706243&dopt=Abstract
Biochem Biophys Res Commun. 1996 Feb 27;219(3):923-9.
The activity of plant-derived antiretroviral proteins MAP30 and GAP31 against herpes simplex virus in vitro.
Bourinbaiar AS, Lee-Huang S.
Department of Biochemistry, New York University School of Medicine, New York 10016, USA.
We examined the effect on anti-HIV proteins MAP30 and GAP31, from Momordica charantia and Gelonium multiflorum, on the infection and replication of Herpes Simplex Viruses (HSV). Human lung WI-38 fibroblasts cultured in the presence of tenfold dilutions of MAP30 or GAP31 were exposed to HSV and viral yield was measured at 24-48 hours by ELISA. The effective concentrations for 50% inhibitions (EC50) were 0.1-0.2 microM for HSV-2, and 0.3-0.5 microM for HSV-1 for MAP30 and GAP31, respectively. In comparison, the EC(50) for acyclovir (ACV), a commonly used anti-HSV drug, was 0.2 and 1.7 microM for HSV-2 and HSV-1, respectively. The cytotoxicity of all three antivirals was negligible and comparable. However, the antiherpetic activity of the plant proteins against acyclovir-resistant strains was two to three logs more potent than ACV. These results suggest that MAP30 and GAP31, previously shown to be active against HIV, may be useful for the therapy of herpesvirus infections.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8645280&dopt=Abstract
Ann Otol Rhinol Laryngol. 1999 May;108(5):423-8.
Therapy of idiopathic sudden sensorineural hearing loss: antiviral treatment of experimental herpes simplex virus infection of the inner ear.
Stokroos RJ, Albers FW, Schirm J.
Department of Otorhinolaryngology, University Hospital Groningen, The Netherlands.
Experimental herpes simplex virus type 1 (HSV-1) labyrinthitis provides a model of idiopathic sudden sensorineural hearing loss (ISSHL). Corticosteroids improve the prognosis for hearing recovery in ISSHL, but the effects of acyclovir are unknown. To establish the therapeutic efficacy of acyclovir (Zovirax) and prednisolone in experimental HSV-1 viral labyrinthitis, we induced HSV-1 labyrinthitis in 12 guinea pigs. Three animals received no treatment, 3 received prednisolone, 3 received acyclovir, and 3 received both. Four other animals served as controls, receiving culture medium only. Hearing, HSV-1 antibody titers, and cochlear damage were evaluated. The HSV-1 labyrinthitis caused hearing loss within 24 hours. Combination treatment consisting of prednisolone and acyclovir resulted in earlier hearing recovery and less extensive cochlear destruction compared to prednisolone or acyclovir as a monotherapy. The beneficial effect of this treatment modality remains to be demonstrated in ISSHL.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10335700&dopt=Abstract
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