ArticleAntimicrobial agents and chemotherapy2014
In vitro combination of anti-cytomegalovirus compounds acting through different targets: role of the slope parameter and insights into mechanisms of Action.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- A systematic review on use of aminoquinolines for the therapeutic management of COVID-19: Efficacy, safety and clinical trials.Life sciences · 2020Pooled it
- Repurposing Anticancer Drugs Targeting the MAPK/ERK Signaling Pathway for the Treatment of Respiratory Virus Infections.International journal of molecular sciences · 2024Review
- Human cytomegalovirus infection enhances 5‑lipoxygenase and cycloxygenase‑2 expression in colorectal cancer.International journal of oncology · 2023Article
- The Trimeric Artesunate Analog TF27, a Broadly Acting Anti-Infective Model Drug, Exerts Pronounced Anti-SARS-CoV-2 Activity Spanning Variants and Host Cell Types.Pharmaceutics · 2022Article
- Therapeutic Drug Monitoring of Ganciclovir: Where Are We?Therapeutic drug monitoring · 2022Review
- Article
- Research Progress in Pharmacological Activities and Applications of Cardiotonic Steroids.Frontiers in pharmacology · 2022Review
- NMPylation and de-NMPylation of SARS-CoV-2 nsp9 by the NiRAN domain.Nucleic acids research · 2021Article
- Outcomes of transplant recipients treated with cidofovir for resistant or refractory cytomegalovirus infection.Transplant infectious disease : an official journal of the Transplantation Society · 2021Article
- The antifungal drug isavuconazole inhibits the replication of human cytomegalovirus (HCMV) and acts synergistically with anti-HCMV drugs.Antiviral research · 2021Article
- Combinatorial Drug Treatments Reveal Promising Anticytomegaloviral Profiles for Clinically Relevant Pharmaceutical Kinase Inhibitors (PKIs).International journal of molecular sciences · 2021Article
- Review
- Artemisinins target the intermediate filament protein vimentin for human cytomegalovirus inhibition.The Journal of biological chemistry · 2020Article
- The Artemisinin-Derived Autofluorescent Compound BG95 Exerts Strong Anticytomegaloviral Activity Based on a Mitochondrial Targeting Mechanism.International journal of molecular sciences · 2020Article
- Highly synergistic drug combination prevents vaginal HIV infection in humanized mice.Scientific reports · 2020Article
- Elucidation of the mechanism of anti-herpes action of two novel semisynthetic cardenolide derivatives.Archives of virology · 2020Article
- Validation and Characterization of Five Distinct Novel Inhibitors of Human Cytomegalovirus.Journal of medicinal chemistry · 2020Article
- Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function.Viruses · 2020Review
- The Use of Antimalarial Drugs against Viral Infection.Microorganisms · 2020Review
- Alphavirus Replication: The Role of Cardiac Glycosides and Ion Concentration in Host Cells.BioMed research international · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Conventional therapy for human cytomegalovirus (CMV) relies on inhibition of the viral DNA polymerase. Ganciclovir (GCV) is the first-line therapy, but when GCV-resistant strains emerge, alternative therapies are extremely limited and are associated with significant toxicities. Combination of anti-CMV agents that act on different targets or stages of virus replication has not been well studied, mostly because of the limited number of anti-CMV agents. We report our investigation of combinations of agents that inhibit CMV by targeting the viral DNA polymerase, cellular kinases, or other cell/virus mechanisms yet to be discovered. The selected compounds differed by the slopes of their dose-response curve: compounds with a slope of 1 (GCV) representing one target or noncooperativity and compounds with high slopes indicating positive cooperativity. Analysis of anti-CMV drug combinations using the Bliss model (which accounts for the slope parameter) distinguished between combinations with synergistic, antagonistic, and additive activities. The combination of GCV and foscarnet was slightly synergistic; strong synergism was found when GCV was used with artemisinin-derived monomers or dimers or the MEK inhibitor U0126. The combination of GCV and cardiac glycosides (digoxin, digitoxin, and ouabain) was additive. The monomeric artemisinin artesunate was synergistic when combined with U0126 or the multikinase inhibitor sunitinib. However, the combination of artemisinin-derived dimers (molecular weights, 606 and 838) and U0126 or sunitinib was antagonistic. These results demonstrate that members of a specific drug class show similar patterns of combination with GCV and that the slope parameter plays an important role in the evaluation of drug combinations. Lastly, antagonism between different classes of CMV inhibitors may assist in target identification and improve the understanding of CMV inhibition by novel compounds.
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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.