Effectiveness of Antiviral Compounds at The Adeno-Herpetic Co-Infection (original) (raw)
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Study of Antiviral Compounds in the Conditions of Mixed Infections
2017
Mixed viral infection is one of the current and unexplored issues of human infectious diseases. A special place in the development of these pathologies is occupied by adeno- and herpes viruses that are able to persist for a long time in a latent condition in the body. There is a huge lack of knowledge about antiviral activities of specific drugs during the mixed infections. The study of know drugs and discovery of new compounds using not only standard mono-infections but also with created mixed infections is a topical and a new direction in antivirus screening. Previously in our department, the models of adeno-herpetic infections in cells of different origins were created and the features of the development of viral infections in these systems were studied. The model of simultaneous adeno-herpetic infection of MDBK cells was used for the analysis of the antiherpetic drug acyclovir (ACV) and for research of new fluorine-containing derivatives of L-phenylalanine (10S-23 and 10S-2...
Antimicrobial Agents and Chemotherapy, 1974
The in vitro susceptibility of type 1 and type 2 strains of Herpesvirus hominis to 9-/3-D-arabinofuranosyladenine (adenine arabinoside, ara-A) was measured in a system where deamination was inhibited. Under these conditions, it was possible to measure the activity of low concentrations of ara-A. It was determined that plaque inhibitory concentration for type 1 viruses was less than 3 ,g/ml for all strains tested. The plaque inhibitory concentration for 7 of 10 type 2 strains was also less than 3 ug/ml. The method used identified and controlled the interaction between antiviral agent (ara-A) and the indicator system, human skin fibroblastic cells. Otherwise, metabolism of ara-A resulted in rapid enzymatic degradation and loss of antiviral activity.
The Tohoku Journal of Experimental Medicine, 1992
9-(2-hydroxyethoxymethyl)guanine (acyclovir, ACV) and novel nucleosides, 9-(2-deoxy-2-hydroxymethyl-/3-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 TKmutants 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. oxetanocin-G ; carbocyclic oxetanocin-G ; ACV ; HSV-1; HSV-2 Herpes simplex virus (HSV) infections such as genital herpes and neonatal HSV infection appear to be increasing (Sullivan-Bolyai et al. 1983) and continue to cause considerable mortality and morbidity (Whitley et al. 1980; Nahmias et
Research in veterinary science, 2017
Caprine herpesvirus 1 (CpHV-1) infection in goats is responsible for genital lesions resembling the lesions induced by herpesvirus 2 in humans (HHV-2). The immunosuppressive drug Mizoribine (MIZ) is able to increase the antiviral activity of Acyclovir (ACV) against herpesvirus infections, raising interesting perspectives on new combined therapeutic strategies. In this study the anti-CpHV-1 activity in vitro of ACV alone or in combination with MIZ was evaluated. ACV (100μg/ml) displayed an antiviral effect on CpHV-1 replication. This inhibitory effect was higher when ACV (100μg/ml) was used in association with MIZ (20μg/ml). Other combinations of ACV and MIZ in various concentrations were not as effective as ACV 100μg/ml/MIZ 20μg/ml. These findings suggest that the association of ACV and MIZ is potentially useful for treatment of genital infection by herpesviruses.
Search of Inhibitors of Herpes Viral Replication: 30 Years After Acyclovir
Biotechnologia Acta, 2013
Analysis of study and using of different chemical compounds as inhibitors of herpes virus replication is given in the review. However, it does not apply for full details of all the studies on active antiherpetic drugs finding. It's been over 30 years since the discovery of the first antiherpetic drugs ? acyclovir. Meanwhile, lots of active chemical compounds appeared that have been brought to the antiviral drugs. An essential understanding of strategies for finding drugs came in, one of which was establishment of depot forms of antiherpetic drugs. On the basis of the vast published experimental material the authors concluded that the study of the herpes virus and search for inhibitors of its replication is still an important issue and requires the efforts of chemists, biologists, pharmacists.
Journal of Medical Virology, 1987
Selective uptake of nucleoside analogues by herpes simplex virus infected cells niay serve as the basis for a specific non-invasive diagnostic test for herpes simplex encephalitis. We have examined the effect of acyclovir on the selective uptake of [ l 3 '11 I-(2'-tluoro-2'-dec~xy-~-D-arabinofuranosyl)-5-i~ouracil in herpes simplex virus infected primary rabbit kidney cells. Infected cells treated with acyclovir continued t o concentrate [ 1 3 ' 11 1-(2'-fluoro-2'-deoxy-P-D-arabinofuranosy1)-Sitxiouracil for up t o 24 h after the addition of the antiviral agent. These results indicated that therapy with acyclovir for as long as 24 h would not prevent the sclcctive trapping of nucleoside analogues. This has important implications for the use of nucleoside analogues in diagnostic brain scans to detect herpes simplex encephalitis.
Biochemical Pharmacology, 1985
The antiherpes agent 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) is a much more potent inhibitor of herpes simplex viruses in vivo than acyclovir, yet both are equally active in vitro against these viruses. To explain this difference, studies were conducted to compare the intracellular metabolism and enzymatic phosphorylation of the two compounds. In herpes type 1 and type 2 infected cells, the levels of DHPG triphosphate were only about 2-fold greater than levels of acyclovir triphosphate at virus-inhibitory concentrations (~< 1/~M). At concentrations > 2.5/~M in herpes type 1 but not in type 2 infected cells, acyclovir phosphorylation was inhibited relative to that of DHPG. When drug was removed after 6 hr from infected cells, acyclovir triphosphate rapidly degraded to acyclovir and was excreted into the culture medium. In contrast, DHPG triphosphate persisted at 60-70% of the original level for 18 hr after drug removal, and DHPG excretion from cells was very slow. This finding could be a key factor to the superior potency of DHPG in animals, despite the fact that blood levels of both compounds fall rapidly after dosing. In uninfected cells, low levels of DHPG and acyclovir triphosphates were produced at 100/.tM concentrations. Phosphorylation of DHPG to mono-, di-and triphosphates by purified viral and cell enzymes was more rapid than that of acyclovir. However, acyclovir triphosphate was a much more potent inhibitor of herpes virus and cell DNA polymerases.