ArticleThe Journal of infectious diseases2010
A new class of dual-targeted antivirals: monophosphorylated acyclovir prodrug derivatives suppress both human immunodeficiency virus type 1 and herpes simplex virus type 2.
Article in The Journal of infectious diseases, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Short communication: T cell activation in HIV-1/herpes simplex virus-2-coinfected Kenyan women receiving valacyclovir.AIDS research and human retroviruses · 2013Trial
- Dual-targeted anti-CMV/anti-HIV-1 heterodimers.Biochimie · 2021Article
- The ProTide Prodrug Technology: From the Concept to the Clinic.Journal of medicinal chemistry · 2018Review
- Virtual Screening of Acyclovir Derivatives as Potential Antiviral Agents: Design, Synthesis, and Biological Evaluation of New Acyclic Nucleoside ProTides.Journal of medicinal chemistry · 2017Article
- Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity.Bioorganic & medicinal chemistry letters · 2015Article
- Prodrugs of phosphonates and phosphates: crossing the membrane barrier.Topics in current chemistry · 2015Review
- Animal and human mucosal tissue models to study HIV biomedical interventions: can we predict success?Journal of the International AIDS Society · 2015Review
- Conformational analysis, molecular structure and solid state simulation of the antiviral drug acyclovir (zovirax) using density functional theory methods.Pharmaceuticals (Basel, Switzerland) · 2014Article
- Update on emerging antivirals for the management of herpes simplex virus infections: a patenting perspective.Recent patents on anti-infective drug discovery · 2013Review
- Use of human mucosal tissue to study HIV-1 pathogenesis and evaluate HIV-1 prevention modalities.Current HIV/AIDS reports · 2013Review
- Microbicides: still a long road to success.Trends in microbiology · 2012Review
- Exploiting the anti-HIV-1 activity of acyclovir: suppression of primary and drug-resistant HIV isolates and potentiation of the activity by ribavirin.Antimicrobial agents and chemotherapy · 2012Article
- Topical tenofovir, a microbicide effective against HIV, inhibits herpes simplex virus-2 replication.Cell host & microbe · 2011Article
- HSV neutralization by the microbicidal candidate C5A.PloS one · 2011Article
- Article
- Phosphoramidates and phosphonamidates (ProTides) with antiviral activity.Antiviral chemistry & chemotherapyReview
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundHuman immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 2 (HSV-2) are responsible for 2 intersecting epidemics in which the disease caused by 1 virus facilitates the transmission of and pathogenesis by the other. Therefore, suppression of one virus infection will affect the other. Acyclovir, a common antiherpetic drug, was shown to directly suppress both viruses in coinfected tissues. However, both antiviral activities of acyclovir are dependent on phosphorylation by the nucleoside kinase activity of coinfecting human herpesviruses.
methodsWe developed acyclovir ProTides, monophosphorylated acyclovir with the phosphate group masked by lipophilic groups to allow efficient cellular uptake, and investigated their antiviral potential in cell lines and in human tissues ex vivo.
resultsAcyclovir ProTides suppressed both HIV-1 and HSV-2 at median effective concentrations in the submicromolar range in ex vivo lymphoid and cervicovaginal human tissues and at 3-12 micromol/L in CD4(+) T cells. Acyclovir ProTides retained activity against acyclovir-resistant HSV-2.
conclusionsAcyclovir ProTides represent a new class of antivirals that suppress both HIV-1 and HSV-2 by directly and independently blocking the key replicative enzymes of both viruses. Further optimization of such compounds may lead to double-targeted antivirals that can prevent viral transmission and treat the 2 synergistic diseases caused by HIV-1 and HSV-2. To our knowledge, the acyclovir ProTides described here represent the first example of acyclic nucleoside monophosphate prodrugs being active against HIV-1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.