ArticleThe Journal of antimicrobial chemotherapy2016
Inhibition of herpes simplex virus type 1 by the CDK6 inhibitor PD-0332991 (palbociclib) through the control of SAMHD1.
Article in The Journal of antimicrobial chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Targeting eEF1A reprograms translation and uncovers broad-spectrum antivirals against cap or mNature communications · 2025Article
- Repurposing of CDK Inhibitors as Host Targeting Antivirals: A Mini- Review.Mini reviews in medicinal chemistry · 2025Review
- Review
- BMS-265246, a Cyclin-Dependent Kinase Inhibitor, Inhibits the Infection of Herpes Simplex Virus Type 1.Viruses · 2023Article
- Cetylpyridinium Chloride-Containing Mouthwashes Show Virucidal Activity against Herpes Simplex Virus Type 1.Viruses · 2023Article
- Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS-CoV-2.MedComm · 2023Review
- Targeting Human Proteins for Antiviral Drug Discovery and Repurposing Efforts: A Focus on Protein Kinases.Viruses · 2023Review
- Human cytomegalovirus UL24 and UL43 products participate in SAMHD1 subcellular localization.Virusdisease · 2022Article
- Kinase Inhibitors as Underexplored Antiviral Agents.Journal of medicinal chemistry · 2022Review
- Dasatinib: effects on the macrophage phospho proteome with a focus on SAMHD1 and HIV-1 infection.Clinical research in HIV/AIDS · 2022Article
- Bioinformatics and System Biology Approach to Reveal the Interaction Network and the Therapeutic Implications for Non-Small Cell Lung Cancer Patients With COVID-19.Frontiers in pharmacology · 2022Article
- Cellular enlargement - A new hallmark of aging?Frontiers in cell and developmental biology · 2022Review
- Targeting Aryl Hydrocarbon Receptor Signaling Enhances Type I Interferon-Independent Resistance to Herpes Simplex Virus.Microbiology spectrum · 2021Article
- Potential drug development and therapeutic approaches for clinical intervention in COVID-19.Bioorganic chemistry · 2021Review
- PIAS1 potentiates the anti-EBV activity of SAMHD1 through SUMOylation.Cell & bioscience · 2021Article
- Dual roles of SAMHD1 in tumor development and chemoresistance to anticancer drugs.Oncology letters · 2021Review
- Repurposing anticancer drugs for the management of COVID-19.European journal of cancer (Oxford, England : 1990) · 2020Review
- SAMHD1 phosphorylation and cytoplasmic relocalization after human cytomegalovirus infection limits its antiviral activity.PLoS pathogens · 2020Article
- Repurposing of Kinase Inhibitors for Treatment of COVID-19.Pharmaceutical research · 2020Review
- Host-Directed Antiviral Therapy.Clinical microbiology reviews · 2020Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesSterile α motif and histidine-aspartate domain-containing protein 1 (SAMHD1) has been shown to restrict retroviruses and DNA viruses by decreasing the pool of intracellular deoxynucleotides. In turn, SAMHD1 is controlled by cyclin-dependent kinases (CDK) that regulate the cell cycle and cell proliferation. Here, we explore the effect of CDK6 inhibitors on the replication of herpes simplex virus type 1 (HSV-1) in primary monocyte-derived macrophages (MDM).
methodsMDM were treated with palbociclib, a selective CDK4/6 inhibitor, and then infected with a GFP-expressing HSV-1. Intracellular deoxynucleotide triphosphate (dNTP) content was determined using a polymerase-based method.
resultsCDK6 inhibitor palbociclib blocked SAMHD1 phosphorylation, intracellular dNTP levels and HSV-1 replication in MDM at subtoxic concentrations. Treatment of MDM with palbociclib reduced CDK2 activation, measured as the phosphorylation of the T-loop at Thr160. The antiviral activity of palbociclib was lost when SAMHD1 was degraded by viral protein X. Similarly, palbociclib did not block HSV-1 replication in SAMHD1-negative Vero cells at subtoxic concentrations, providing further evidence for a role of SAMHD1 in mediating the antiviral effect.
conclusionsSAMHD1-mediated HSV-1 restriction is controlled by CDK and points to a preferential role for CDK6 and CDK2 as mediators of SAMHD1 activation. Similarly, the restricting activity of SAMHD1 against DNA viruses suggests that control of dNTP availability is the major determinant of its antiviral activity. This is the first study describing the anti-HSV-1 activity of palbociclib.
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