ArticleAntimicrobial agents and chemotherapy2014
Antiviral activity of (+)-rutamarin against Kaposi's sarcoma-associated herpesvirus by inhibition of the catalytic activity of human topoisomerase II.
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 17 papers.
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17 citing papers in PubMed, 40 citations in OpenAlex.
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- Coumarins as Fungal Metabolites with Potential Medicinal Properties.Antibiotics (Basel, Switzerland) · 2022Review
- In silico analysis and identification of antiviral coumarin derivatives against 3-chymotrypsin-like main protease of the novel coronavirus SARS-CoV-2.Molecular diversity · 2022Article
- Natural Products and Their Derivatives against Human Herpesvirus Infection.Molecules (Basel, Switzerland) · 2021Review
- Recent Advances in Developing Treatments of Kaposi's Sarcoma Herpesvirus-Related Diseases.Viruses · 2021Review
- Furanocoumarins fromMolecules (Basel, Switzerland) · 2021Article
- Combination of coumarin and doxorubicin induces drug-resistant acute myeloid leukemia cell death.Heliyon · 2021Article
- Synthesis of novel coumarin analogues: Investigation of molecular docking interaction of SARS-CoV-2 proteins with natural and synthetic coumarin analogues and their pharmacokinetics studies.Saudi journal of biological sciences · 2021Article
- Discovering new PI3Kα inhibitors with a strategy of combining ligand-based and structure-based virtual screening.Journal of computer-aided molecular design · 2018Article
- Rutamarin, an Active Constituent fromPharmacognosy magazine · 2017Article
- Therapeutic potential of coumarins as antiviral agents.European journal of medicinal chemistry · 2016Review
- Discovering new mTOR inhibitors for cancer treatment through virtual screening methods and in vitro assays.Scientific reports · 2016Article
- Phosphoproteomic Profiling Reveals Epstein-Barr Virus Protein Kinase Integration of DNA Damage Response and Mitotic Signaling.PLoS pathogens · 2015Article
- Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
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Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) is an etiological agent of several AIDS-associated malignancies, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). Its lytic replication cycle has been proven to be critical for the pathogenesis of KSHV-associated diseases. In KS lesions, lytic viral replication, production of virion particles, and reinfection of endothelial cells are essential to sustain the population of infected cells that otherwise would be quickly lost as spindle cells divide. Thus, antivirals that block KSHV replication could be a strategy in the treatment of KSHV-associated diseases. However, there is no effective anti-KSHV drug currently available. Our previous work showed that human topoisomerase II (Topo II) is indispensable for KSHV lytic replication and is suggested to be an effective target for antiviral drugs. Here, we report the discovery and characterization of a novel catalytic inhibitor of human Topo IIα, namely, (+)-rutamarin. The binding mode of (+)-rutamarin to the ATPase domain of human Topo IIα was established by docking and validated by molecular dynamics (MD) simulations. More importantly, (+)-rutamarin efficiently inhibits KSHV lytic DNA replication in BCBL-1 cells with a half-maximal inhibitory concentration (IC50) of 1.12 μM and blocks virion production with a half-maximal antiviral effective concentration (EC50) of 1.62 μM. It possesses low cytotoxicity, as indicated by the selectivity index (SI) of 84.14. This study demonstrated great potential for (+)-rutamarin to become an effective drug for treatment of human diseases associated with KSHV infection.
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