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1.
Biomolecules ; 13(7)2023 07 08.
Article in English | MEDLINE | ID: mdl-37509131

ABSTRACT

The COVID-19 pandemic has highlighted an urgent need to discover and test new drugs to treat patients. Metal-based drugs are known to interact with DNA and/or a variety of proteins such as enzymes and transcription factors, some of which have been shown to exhibit anticancer and antimicrobial effects. BOLD-100 (sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)]dihydrate) is a novel ruthenium-based drug currently being evaluated in a Phase 1b/2a clinical trial for the treatment of advanced gastrointestinal cancer. Given that metal-based drugs are known to exhibit antimicrobial activities, we asked if BOLD-100 exhibits antiviral activity towards SARS-CoV-2. We demonstrated that BOLD-100 potently inhibits SARS-CoV-2 replication and cytopathic effects in vitro. An RNA sequencing analysis showed that BOLD-100 inhibits virus-induced transcriptional changes in infected cells. In addition, we showed that the antiviral activity of BOLD-100 is not specific for SARS-CoV-2, but also inhibits the replication of the evolutionarily divergent viruses Human Immunodeficiency Virus type 1 and Human Adenovirus type 5. This study identifies BOLD-100 as a potentially novel broad-acting antiviral drug.


Subject(s)
Antineoplastic Agents , COVID-19 , Humans , SARS-CoV-2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Pandemics , Antineoplastic Agents/pharmacology , Virus Replication
2.
Urol Case Rep ; 48: 102388, 2023 May.
Article in English | MEDLINE | ID: mdl-37009234

ABSTRACT

We report a unique case of botryoid-type embryonal RMS of the proximal and mid ureter in a pregnant 29-year-old woman. The ureteral polyp consisted of a malignant small blue round cell tumor with a myxoid background and contained evidence of foci of immature cartilage and aggregates of epithelial cells reminiscent of hair follicle. Immunohistochemical stains for myogenin and desmin confirmed skeletal muscle, or rhabdomyoblastic, differentiation. The compact epithelial cell fragments reminiscent of hair follicle differentiation were positive for p40. Treatment included 6 cycles of adjuvant chemotherapy (vincristine, actinomycin and cyclophosphamide (VAC). No recurrent or metastatic disease was identified post-surgery.

3.
Cells ; 10(9)2021 09 13.
Article in English | MEDLINE | ID: mdl-34572049

ABSTRACT

Survival following Ebola virus (EBOV) infection correlates with the ability to mount an early and robust interferon (IFN) response. The host IFN-induced proteins that contribute to controlling EBOV replication are not fully known. Among the top genes with the strongest early increases in expression after infection in vivo is IFN-induced HERC5. Using a transcription- and replication-competent VLP system, we showed that HERC5 inhibits EBOV virus-like particle (VLP) replication by depleting EBOV mRNAs. The HERC5 RCC1-like domain was necessary and sufficient for this inhibition and did not require zinc finger antiviral protein (ZAP). Moreover, we showed that EBOV (Zaire) glycoprotein (GP) but not Marburg virus GP antagonized HERC5 early during infection. Our data identify a novel 'protagonist-antagonistic' relationship between HERC5 and GP in the early stages of EBOV infection that could be exploited for the development of novel antiviral therapeutics.


Subject(s)
Ebolavirus/physiology , Glycoproteins/metabolism , Hemorrhagic Fever, Ebola/prevention & control , Interferons/pharmacology , Intracellular Signaling Peptides and Proteins/metabolism , Virion/drug effects , Virus Replication , Antiviral Agents/pharmacology , Glycoproteins/genetics , HeLa Cells , Hemorrhagic Fever, Ebola/metabolism , Hemorrhagic Fever, Ebola/virology , Humans , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Intracellular Signaling Peptides and Proteins/genetics , Virion/metabolism
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