Resistance of herpes simplex virus type 1 against different phosphonylmethoxyalkyl derivatives of purines and pyrimidines due to specific mutations in the viral DNA polymerase gene

Andrei, Gracíela; Snoeck, Robert; Clercq, Erik De; Esnouf, Robert; Fiten, Pierre; Opdenakker, Ghislain

doi:10.1099/0022-1317-81-3-639

Cited by 58 publications

(66 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Confluent monolayers were inoculated with 100 CCID50 of virus (50 % cell culture infectious dose, 1 CCID50 being the amount of virus that infects 50 % of the cell culture) in the presence of serial dilutions of the synthetic peptides [49][50][51]. The antiviral activity was determined by the ability to inhibit the virusinduced cytopathogenic effect in the different cell lines (HeLa cells for infection with RSV and HEL cells for infection with HSV-1, HSV-2, ADV-2 and VV).…”

Section: Antiviral and Cytotoxicity Assaysmentioning

confidence: 99%

Basic chemokine-derived glycosaminoglycan binding peptides exert antiviral properties against dengue virus serotype 2, herpes simplex virus-1 and respiratory syncytial virus

Vanheule

Vervaeke

Mortier

et al. 2016

Biochemical Pharmacology

Self Cite

View full text Add to dashboard Cite

Chemokines attract leukocytes to sites of infection in a G protein-coupled receptor (GPCR) and glycosaminoglycan (GAG) dependent manner. Therefore, chemokines are crucial molecules for proper functioning of our antimicrobial defense mechanisms. In addition, some chemokines have GPCRindependent defensin-like antimicrobial activities against bacteria and fungi. Recently, high affinity for GAGs has been reported for the positively charged COOH-terminal region of the chemokine CXCL9. In addition to CXCL9, also CXCL12γ has such a positively charged COOH-terminal region with about 50 % positively charged amino acids. In this report, we compared the affinity of COOH-terminal peptides of These short chemokine-derived peptides may be lead molecules for the development of novel antiviral agents.

show abstract

Section: Antiviral and Cytotoxicity Assaysmentioning

confidence: 99%

Basic chemokine-derived glycosaminoglycan binding peptides exert antiviral properties against dengue virus serotype 2, herpes simplex virus-1 and respiratory syncytial virus

Vanheule

Vervaeke

Mortier

et al. 2016

Biochemical Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Mutations located in conserved region II of the HSV DNA pol gene are frequently associated with resistance to ACV and pyrophosphate analogues (1,22,34,42). Two (A719T and S724N) of the four mutations located within this region conferred similar phenotypes and were also associated with ADV resistance.…”

Section: Susceptibility Of Hsv Recombinants To Antiviralsmentioning

confidence: 99%

“…Those mutations were selected on the basis of their presence within previously reported clinical HSV isolates (6,27,43) or within laboratory-derived HSV strains (1,22,28,29,32,34,36). Furthermore, a few HSV-1 DNA Pol mutants were generated based on the presence of similar mutations within the HCMV DNA pol gene (4,5,12,31,44).…”

Section: Susceptibility Of Hsv Recombinants To Antiviralsmentioning

confidence: 99%

“…When not lethal, some mutations within this region have been shown to confer resistance to pyrophosphate analogues (22,29,33,34). Only a few drugresistant mutations have been described within the other conserved regions or outside such regions (1,6,18,22,27,36,43). Because of the reported viral polymorphism (11,32), the role of any DNA Pol mutation must be carefully assessed.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Drug Resistance Patterns of Recombinant Herpes Simplex Virus DNA Polymerase Mutants Generated with a Set of Overlapping Cosmids and Plasmids

Bestman-Smith

Boivin

2003

J Virol

View full text Add to dashboard Cite

Herpes simplex virus (HSV) DNA polymerase (Pol) mutations can confer resistance to all currently available antiherpetic drugs. However, discrimination between mutations responsible for drug resistance and those that are part of viral polymorphism can be difficult with current methodologies. A new system is reported for rapid generation of recombinant HSV type 1 (HSV-1) DNA Pol mutants based on transfection of a set of overlapping viral cosmids and plasmids. With this approach, twenty HSV-1 recombinants with single or dual mutations within the DNA pol gene were successfully generated and subsequently evaluated for their susceptibilities to acyclovir (ACV), foscarnet (FOS), cidofovir (CDV), and adefovir (ADV). Mutations within DNA Pol conserved regions II (A719T and S724N), VI (L778M, D780N, and L782I), and I (F891C) were shown to induce cross-resistance to ACV, FOS, and ADV, with two of these mutations (S724N and L778M) also conferring significant reduction in CDV susceptibility. Mutant F891C was associated with the highest levels of resistance towards ACV and FOS and was strongly impaired in its replication capacity. One mutation (D907V) lying outside of the conserved regions was also associated with this ACV-, FOS-, and ADV-resistant phenotype. Some mutations (K522E and Y577H) within the ␦-region C were lethal, whereas others (P561S and V573M) induced no resistance to any of the drugs tested. Recombinants harboring mutations within conserved regions V (N961K) and VII (Y941H) were resistant to ACV but susceptible to FOS. Finally, mutations within conserved region III were associated with various susceptibility profiles. This new system allows a rapid and accurate evaluation of the functional role of various DNA Pol mutations, which should translate into improved management of drug-resistant HSV infections.Two categories of antivirals are available for the management of herpes simplex virus (HSV) infections. The first class of agents includes molecules that, following viral and/or cellular phosphorylation, compete with natural deoxynucleoside triphosphates for incorporation into the elongating viral DNA chain. Acyclovir (ACV) and penciclovir with their respective prodrugs, valacyclovir and famciclovir, are agents representative of this class and are considered the standard therapy for HSV infections. Although not indicated for the treatment of HSV infections, cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine; CDV] and adefovir [9-(2-phosphonylmethoxyethyl)adenine; ADV] are acyclic nucleoside phosphonate derivatives that, once activated, are also alternative substrates for the viral DNA polymerase (Pol). The other class of HSV inhibitors consists of pyrophosphate analogues such as foscarnet (FOS). These agents are direct noncompetitive inhibitors of the viral DNA Pol. A single DNA Pol mutation could thus confer resistance to more than one antiviral depending on the specific drug binding site on the enzyme.Resistance to ACV, the most widely used anti-HSV agent, is due mainly to mutations in the viral t...

show abstract

“…In vivo resistance to CDV has been described but appears uncommon (Wyles et al, 2005) although mutations in pol conferring resistance have been described (Andrei et al, 2000). However, in vitro sensitivity to CDV is not always accompanied by a clinical response (Chen et al, 2000), a discrepancy that can be accounted for in part by heterogeneity within the virus population found within a lesion, i.e.…”

Section: Management Of Resistant Virusmentioning

confidence: 93%

Management of multidrug‐resistant viruses in the immunocompromised host

Sellar

Peggs

2011

Br J Haematol

View full text Add to dashboard Cite

show abstract

Resistance of herpes simplex virus type 1 against different phosphonylmethoxyalkyl derivatives of purines and pyrimidines due to specific mutations in the viral DNA polymerase gene

Cited by 58 publications

References 44 publications

Basic chemokine-derived glycosaminoglycan binding peptides exert antiviral properties against dengue virus serotype 2, herpes simplex virus-1 and respiratory syncytial virus

Basic chemokine-derived glycosaminoglycan binding peptides exert antiviral properties against dengue virus serotype 2, herpes simplex virus-1 and respiratory syncytial virus

Drug Resistance Patterns of Recombinant Herpes Simplex Virus DNA Polymerase Mutants Generated with a Set of Overlapping Cosmids and Plasmids

Management of multidrug‐resistant viruses in the immunocompromised host

Contact Info

Product

Resources

About