"The end of innocence" revisited: resistance of herpesviruses to antiviral drugs

a b s t r a c tQuinoxaline derivatives are an important class of heterocycle compounds, where N replaces some carbon atoms in the ring of naphthalene. Its molecular formula is C 8 H 6 N 2 , formed by the fusion of two aromatic rings, benzene and pyrazine. It is rare in natural state, but their synthesis is easy to perform.In this review the State of the Art will be presented, which includes a summary of the progress made over the past years in the knowledge of the structure and mechanism of the quinoxaline and quinoxaline derivatives, associated medical and biomedical value as well as industrial value.Modifying quinoxaline structure it is possible to obtain a wide variety of biomedical applications, namely antimicrobial activities and chronic and metabolic diseases treatment.

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“…However, there are drug-resistant strains of HSV emerging and increasing [33,36], leading to the search of new antiviral drugs.…”

Section: Antiviral Activitymentioning

confidence: 99%

Quinoxaline, its derivatives and applications: A State of the Art review

Pereira

Moura

Cordeiro

et al. 2015

European Journal of Medicinal Chemistry

385

124

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“…These drugs are direct inhibitors of the viral DNA polymerase by binding to the site involved in releasing the pyrophosphate product of DNA synthesis (Eriksson et al, 1980). Compounds representative of the second category are the nucleoside analogues such as ACY, ganciclovir (GCV), brivudin (BVDU) and penciclovir (PCV), which depend on the virus-induced thymidine kinase (TK) for their antiviral action (Collins & Darby, 1991;Field & Biron, 1994). Conversion to the monophosphate forms of these nucleoside analogues (and for BVDU also to the diphosphate) is catalysed by the viral TK; further phosphorylation to their di-and triphosphate forms is catalysed by cellular enzymes, the triphosphate being capable of inhibiting the DNA polymerase.…”

mentioning

confidence: 99%

Differential Susceptibility of Several Drug-Resistant Strains of Herpes Simplex Virus Type 2 to Various Antiviral Compounds

Andrei

Snoeck

Clercq

1997

Antivir Chem Chemother

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SummaryDrug-resistant herpes simplex virus type 2 (HSY-2) strains were obtained under the selective pressure of acyclovir, ganciclovir, brivudin,foscarnet, 2-phosphonylmethoxyethyl (PME) derivatives of adenine (PMEA) and 2,6-diaminopurine (PMEDAPl, and 3-hydroxy-2-phosphonylmethoxypropyl (HPMP) derivatives of adenine (HPMPA) and cytosine (HPMPC; cidofovir). A significant degree of cross-resistance between HPMPC and HPMPA on the one hand, and between PMEA, PMEDAP and foscarnet on the other, was noted, suggesting a different modeof interaction of the PME and HPMP derivativesat the DNA polymerase level. The results described here with HSY-2 agree with the published results for HSY-1 and human cytomegalovirus., Keywords: herpes simplex virus; resistance; acyclic nucleoside phosphonates; acyclovir; cidofovir.Herpes simplex virus (HSV) resistance to antiviral drugs is nowadays recognized as an important problem. In vitro selection of HSV strains resistant to antiviral compounds was described in the early 1980s. Drug-resistant HSV strains were also recovered from patients, but these viruses did not cause progressive disease in the immunocompetent host. However, in the immunosuppressed patient the emergence of drug-resistant HSV strains may lead to devastating or fatal disease. Acyclovir (ACV) has been shown to be effective in the prophylaxis and treatment of mucocutaneous HSV infections, and it has become the drug of choice in the treatment of HSV infections in the immunocompromised patient. ACV-resistant (Acvr) HSV strains have been recovered from bone marrow transplant recipients, solid organ transplant recipients and AIDS patients (Crumpacker et al., 1982; Vinckier etal., 1987; Erlich etal., 1989;Safrin et al., 1990). ACV resistance in immunocompromised patients most often occurs after prolonged courses of intermittent or continuous ACV administration for the treatment of recurrent episodes of HSV in the setting of a high degree of immunosuppression. Alternative antiviral agents for the treatment of Acvr HSV infections are foscarnet (phosphonoformic acid; PFA) and vidarabine (araA), PFA being the drug of choice for the treatment of such infections due to its better efficacy and lower toxicity when compared to araA (Vinckier et al., 1987;Safrin et al., 1991). However, PFAr HSV strains have also been recovered from immunocompromised patients . An alternative for the treatment ofACvr and/or PFAr HSV infections are the acyclic nucleoside phosphonates. The lead compound of this series, (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC; cidofovir), has proved effective in the treatment of persistent mucocutaneous infections caused by either ACvr or ACVrlPFN HSV (Snoeck etal., 1993(Snoeck etal., ,1994(Snoeck etal., ,1996Lalezari et al., 1994;Andrei et al., 1995). Cidofovir has recently been approved for the treatment of cytomegalovirus retinitis in AIDS patients (Lalezari et al., 1997).We have already reported the susceptibilities of several drug-resistant HSV-1 and human cytomegalovirus (HCMV) strains to v...

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“…16 There is an increasing need for search of new compounds which show antiviral activity because as the treatment of viral infections with the marketed available antiviral drugs is often not good enough due to the development of viral resistance & in recurrent infection in immunocompromised patients. 17,18 Ethnopharmacology provides an alternative approach for the new discovery of antiviral agents, namely it includes the study of medicinal plants with a history of traditional use of plant as a potential source of substances which show significant pharmacological and biological activities. 19 HIV protease belongs to the family of aspartic proteases and has similar structural composition and mechanism resembles to aspartic protease enzymes.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Rumex Vesicarius Linn and Symplocos Racemosa Roxb as Probable Hiv-Protease Inhibitors

Manure¹,

Naikwade²

2017

Int. Res. J. Pharm.

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The objective of the present study to evaluate in-vitro antiviral activity of different extracts of leaves of Rumex vesicarius Linn and Symplocos racemosa Roxb. In this study in-vitro antiviral activity was assayed by pepsin. Pepsin was used as a substitute for HIV-protease to evaluate inhibitory activity of these plants, as pepsin has close resemblance with HIV-protease in proteolytic activity. We have evaluated antiviral activity of different extracts of leaves of Rumex vesicarius Linn and Symplocos racemosa Roxb. But neither different extract of leaves of Rumex vesicarius Linn shows antiviral activity or protease inhibitory activity nor different extract of leaves of Symplocos racemosa Roxb. We have used pepstatin A as a standard (Positive control) which is a natural inhibitor of pepsin enzyme. The study demonstrated that the different extracts of Rumex vesicarius Linn and Symplocos racemosa Roxb did not show antiviral activity or protease inhibitory activity.

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"The end of innocence" revisited: resistance of herpesviruses to antiviral drugs

Cited by 171 publications

References 131 publications

Quinoxaline, its derivatives and applications: A State of the Art review

Quinoxaline, its derivatives and applications: A State of the Art review

Differential Susceptibility of Several Drug-Resistant Strains of Herpes Simplex Virus Type 2 to Various Antiviral Compounds

Evaluation of Rumex Vesicarius Linn and Symplocos Racemosa Roxb as Probable Hiv-Protease Inhibitors

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