Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

9-(2-hydroxyethoxymethyl)guanine (acyclovir, ACV) and novel nucleosides, 9-(2-deoxy-2-hydroxymethyl-beta-D-erythro-oxetanocyl)guanine (oxetanocin-G, OXT-G) and (+)-9-[(1R, 2R, 3S)-2, 3-bis(hydroxymethyl)cyclobutyl]guanine (carbocyclic oxetanocin-G, carbocyclic OXT-G) possessed substantial antiviral activities against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). ACV inhibited only viral thymidine kinase positive (TK+) herpes viruses, although the latter two compounds inhibited the replications of the TK deficient (TK-) mutants of HSV-1 and HSV-2 as well as the TK+ parent strains in vitro. The TK- mutants of HSV-1 and HSV-2 (HSV-1 TK- and HSV-2 TK-) were as susceptible to OXT-G as the TK parent strains. However, the TK- mutants were less susceptible to carbocyclic OXT-G than the TK+ parent strains. We demonstrated synergistic inhibition of the replications of HSV-1 and HSV-2 by ACV and OXT-G in combination, additive inhibition of HSV-1 and HSV-2 by ACV and carbocyclic OXT-G in combination, synergistic inhibition of HSV-1 by OXT-G and carbocyclic OXT-G in combination, and additive inhibition of HSV-2 by these two compounds. We investigated the metabolism of ACV and OXT-G in HSV-1 TK(+)-, HSV-1 TK(-)- and mock-infected Vero cells by thin layer chromatography. ACV-triphosphate increased more in HSV-1 TK(+)-infected Vero cells than in HSV-1 TK(-)- and mock-infected Vero cells. The metabolism of OXT-G had almost the same pattern in HSV-1 TK(+)-, HSV-1 TK(-)- and mock-infected Vero cells. These results suggest that ACV is phosphorylated by virus-induced TK, and OXT-G is phosphorylated by cellular nucleoside and nucleotide kinases.
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PMID:Effects of acyclovir, oxetanocin-G, and carbocyclic oxetanocin-G in combinations on the replications of herpes simplex virus type 1 and type 2 in Vero cells. 133 51

Several new nucleosides with an oxetanosyl-N-glycoside group, named oxetanocins, were evaluated for their antiviral activities against varicella-zoster virus (VZV) in human embryo lung cells. 9-(2-deoxy-2-hydroxy-methyl-beta-D-erythro-oxetanosyl)guanine (OXT-G) and 9-(2-deoxy-2-hydroxymethyl-beta-D-erythro-oxetanosyl)-2- aminoadenine were effective against not only thymidine kinase-positive (TK+) VZV (YS strain) but also thymidine kinase-negative (TK-) VZV (YSR strain), whereas carbocyclic OXT-G was effective against TK+ VZV but not against TK- VZV. [3H]OXT-G was incorporated into TK+ VZV-infected cells and TK- VZV-infected cells more than into mock-infected cells and was converted into the triphosphate form.
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PMID:Antiviral activity of oxetanocins against varicella-zoster virus. 165 65

Sixteen freshly isolated varicella-zoster virus (VZV) strains were evaluated in vitro, in parallel with two reference strains expressing a functional thymidine kinase (TK+) (Oka and YS) and two thymidine kinase-deficient mutants (TK-) (07-1 and YS-R), for their susceptibility to a broad range of antiviral compounds. The following compounds were included: acyclovir (ACV), brivudine (BVDU), sorivudine (BVaraU), other BVDU congeners such as BTDU, CTDU, CVDC and CVDU, ganciclovir (GCV), FIAC, araT, araA, araC, foscarnet (PFA), phosphonoacetic acid (PAA), the acyclic nucleoside phosphonates HPMPC, cHPMPC, HPMPA, cHPMPA, HPMPc3A, PMEA and PMEDAP, the N7-isomeric acyclic nucleoside analogue N7AP, penciclovir (PCV), compounds 882C87 and H2G and two oxetanocin derivatives OXT-A and OXT-G. Fourteen of the 16 clinical isolates displayed the following order of decreasing selectivity against VZV: BVaraU > BVDU > CVDU approximately CVDC > H2G > N7AP approximately CTDU approximately BTDU approximately OXT-G approximately 882C87 > ACV > FIAC approximately araT > HPMPC approximately cHPMPC approximately HPMPA approximately HPMPc3A approximately cHPMPA > PCV approximately GCV approximately OXT-A > PMEDAP approximately PMEA > PFA approximately PAA approximately araA > araC. Two VZV strains (isolated from the cerebrospinal fluid of an AIDS patient) that were shown to have a truncated TK were clearly resistant to all the compounds that need the viral TK for their phosphorylation, while sensitivity to the acyclic nucleoside phosphonates, PFA, PAA, OXT-A and araA, remained unchanged. A slight (5- and 10-fold) increase was noted in the 50% inhibitory concentration of N7AP and OXT-G, respectively, for the TK- VZV strains as compared to the TK+ VZV strains. Ganciclovir and FIAC also showed a marked decrease in their activity against these two strains, but this was not as pronounced as for the other viral TK-dependent drugs. From our results, it appears that although acyclic nucleoside phosphonates may not have as favourable a therapeutic index as drugs requiring the viral TK, they should be considered for the treatment of TK- VZV life-threatening infections that are resistant to the viral TK-dependent drugs.
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PMID:Comparative activity of selected antiviral compounds against clinical isolates of varicella-zoster virus. 764 95

The inhibitory activities of acyclovir (ACV), 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU), ganciclovir (GCV), 9-(2-deoxy-2-hydroxymethyl-beta-D-erythro-oxetanosyl)guanine (OXT-G), and (+)-9-[(1R,2R,3S)-2,3-bis(hydroxymethyl)Cyclobutyl]guanine (cOXT-G) on the replication of wild-type and thymidine kinase (TK)-negative strains of herpes simplex virus types 1 and 2 and varicella-zoster virus (VZV) and the wild-type strain of human cytomegalovirus were tested to clarity whether the phosphorylation of these compounds is catalyzed by viral TK or other enzymes. ACV and BV-araU had little effect on the replication of TK-negative virus strains. On the other hand, GCV, OXT-G, and cOXT-G inhibited the replication of TK-negative VZV at concentrations 10 times higher than those at which they inhibited wild-type VZV, indicating that a kinase other than TK phosphorylates GCV and OXT-G in VZV-infected cells. GCV phosphorylation activity was not detected in VZV-infected cell lysates; therefore, this activity was evaluated in COS 1 cells expressing viral TK and viral protein kinase (PK). The COS 1 cells expressing VZV TK were shown to be susceptible to all compounds tested. In contrast, VZV Pk-expressing COS 1 cells were susceptible to only GCV, OXT-G, and cOXT-G. These results suggest that VZV PK phosphorylates some nucleoside analogs, for example, GCV, OXT-G, and cOXT-G. This phosphorylation pathway may be important in the anti-VZV activities of some nucleoside analogs.
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PMID:Analysis of phosphorylation pathways of antiherpesvirus nucleosides by varicella-zoster virus-specific enzymes. 884 52