ArticleCell chemical biology2016
Drug Repurposing Approach Identifies Inhibitors of the Prototypic Viral Transcription Factor IE2 that Block Human Cytomegalovirus Replication.
Article in Cell chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
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- Transcriptional Differential Analysis of Nitazoxanide-Mediated Anticanine Parvovirus Effect in F81 Cells.Viruses · 2024Article
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- Discovery of novel SARS-CoV-2 inhibitors targeting the main protease MAntiviral research · 2022Article
- Identification and characterization of bisbenzimide compounds that inhibit human cytomegalovirus replication.The Journal of general virology · 2021Article
- Natural Products and Their Derivatives against Human Herpesvirus Infection.Molecules (Basel, Switzerland) · 2021Review
- Valspodar limits human cytomegalovirus infection and dissemination.Antiviral research · 2021Article
- Main protease inhibitors and drug surface hotspots for the treatment of COVID-19: A drug repurposing and molecular docking approach.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Article
- The antifungal drug isavuconazole inhibits the replication of human cytomegalovirus (HCMV) and acts synergistically with anti-HCMV drugs.Antiviral research · 2021Article
- The Clinically Approved Antifungal Drug Posaconazole Inhibits Human Cytomegalovirus Replication.Antimicrobial agents and chemotherapy · 2020Article
- Review
- Drug repurposing of nitazoxanide: can it be an effective therapy for COVID-19?Journal, genetic engineering & biotechnology · 2020Review
- 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
- Article
- Article
- Drug Repurposing for Viral Infectious Diseases: How Far Are We?Trends in microbiology · 2018Review
- Inhibition of vaccinia virus replication by nitazoxanide.Virology · 2018Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
New targets for antiviral strategies are needed against human cytomegalovirus (HCMV), a major human pathogen. A cell-based screen aimed at finding inhibitors of the viral transcription factor Immediate-Early 2 (IE2) was performed in HCMV-infected cells expressing EGFP under the control of an IE2-inducible viral promoter. Screening of a library of bioactive small molecules led to the identification of several compounds able to inhibit EGFP expression and also HCMV replication with potency in the low-micromolar range. Follow-up studies with four selected hits indicated that they all block viral DNA synthesis as well as viral Early and Late gene expression. Furthermore, mechanistic studies confirmed that the compounds specifically act via inhibition of IE2 transactivating activity, thus blocking viral Early gene expression and the progression of virus replication. These results provide proof of concept for identifying small molecules that modulate the activity of a microbial transcription factor to control pathogen replication.
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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.