Publications by authors named "Brett A Duguay"
Article Synopsis
- - Coronavirus replication relies on the cleavage of polyproteins into non-structural proteins, facilitated by two human coronavirus proteases, M and PL.
- - A phenothiazine urea derivative was discovered that inhibits both SARS-CoV-2 proteases, showing potential to bind similar proteases from other coronaviruses (HCoV-229E and HCoV-OC43).
- - The compound demonstrated broad antiviral activity against these coronaviruses by blocking early viral replication stages and reducing the formation of replication structures and viral RNA synthesis.
Article Synopsis
- There is a pressing need for new antiviral drugs, and research shows that the drug 6-thioguanine (6-TG) can inhibit the replication of viruses like HCoV-OC43 and SARS-CoV-2.
- 6-TG disrupts early infection processes by causing issues with the Spike protein, preventing the viruses from effectively replicating and assembling.
- The antiviral activity of 6-TG requires it to be converted into a specific nucleotide form, and further studies indicate that it might target an unidentified small GTPase, presenting a potential avenue for developing host-targeted antiviral therapies.
Article Synopsis
- Photodynamic inactivation (PDI) is a technique that uses a photosensitizer, like the botanical extract PhytoQuin, along with light and oxygen to generate reactive oxygen species (ROS) that can inactivate microorganisms, including viruses.
- Research has shown that photoactivated PhytoQuin has antiviral effects against human coronaviruses, specifically HCoV-229E and HCoV-OC43, inhibiting their replication in cultured cells in a light-dependent manner.
- The study also found that PDI damages the viral integrity of coronaviruses, allowing for the breakdown of their RNA, and identified emodin, a component of PhytoQuin, as being critical to its antiviral activity.
Article Synopsis
- Influenza A viruses (IAVs) manipulate host cellular mechanisms to evade antiviral responses and enhance viral protein production, particularly affecting the translation process in infected cells.
- The study identified two thiopurines, 6-thioguanine (6-TG) and 6-thioguanosine (6-TGo), which can induce the formation of stress granules and inhibit IAV replication specifically by disrupting the synthesis of key glycoproteins, hemagglutinin (HA) and neuraminidase (NA), without affecting other viral proteins.
- The activation of the unfolded protein response (UPR) emerged as a significant factor in this process, with the study suggesting that manipulating UPR pathways could enhance
Article Synopsis
- * They play a crucial role in various health conditions, including asthma, allergies, heart disease, Alzheimer's, and cancer, making them significant targets for drug discovery and diagnostics.
- * Recent research is exploring nanotechnologies to modify mast cell functions, highlighting their potential as tools in understanding mast cell biology.
Article Synopsis
- Research into broadly-acting antivirals is necessary due to drug resistance developing from the long-term use of existing treatments for herpes simplex virus (HSV) infections like acyclovir and foscarnet.
- Orthoquin, a plant extract with photosensitizing properties, has shown promising antiviral effects against HSV-1 and HSV-2 when activated by light, effectively inhibiting viral infection in a dose-dependent manner.
- The inactivation mechanism of Orthoquin may involve damaging viral attachment proteins, as higher doses appear to affect certain HSV-1 proteins, and the treatment also shows efficacy against other viruses like adenovirus and vesicular stomatitis virus.
Article Synopsis
- Mast cells play a critical role in allergies and asthma, making it essential to understand the molecular mechanisms that regulate them.
- Traditional methods for delivering DNA to human mast cells have been ineffective, which prompted this study to explore lipid nanoparticles (LNPs) as an alternative.
- The research successfully demonstrated that LNPs significantly increased plasmid DNA delivery into mast cell lines, achieving up to 53.2% transfection efficiency while maintaining over 65% cell viability, surpassing previous methods like Lipofectamine 3000.
Unlabelled: The herpes simplex virus (HSV) virion host shutoff (vhs) RNase destabilizes cellular and viral mRNAs, suppresses host protein synthesis, dampens antiviral responses, and stimulates translation of viral mRNAs. vhs mutants display a host range phenotype: translation of viral true late mRNAs is severely impaired and stress granules accumulate in HeLa cells, while translation proceeds normally in Vero cells. We found that vhs-deficient virus activates the double-stranded RNA-activated protein kinase R (PKR) much more strongly than the wild-type virus does in HeLa cells, while PKR is not activated in Vero cells, raising the possibility that PKR might play roles in stress granule induction and/or inhibiting translation in restrictive cells.
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- Mitochondrial DNA (mtDNA) is crucial for cellular energy production and is maintained in specific structures called nucleoids, regulated by the protein TFAM.
- Moderate mtDNA stress, arising from TFAM deficiency, activates a cellular antiviral response that increases the expression of certain interferon-stimulated genes.
- The study highlights the role of mitochondria in innate immunity and suggests that monitoring mtDNA stability is key for effective antiviral responses, especially during herpesvirus infections.
Article Synopsis
- Infection with herpes simplex virus type 1 (HSV-1) leads to the quick loss of mitochondrial DNA (mtDNA) from host cells, primarily triggered by the viral enzyme UL12.5.
- Research revealed that although UL12.5 is crucial for mtDNA depletion, an HSV-1 variant using a different enzyme (UL98) could replicate effectively without depleting mtDNA, suggesting that mtDNA loss is not essential for viral replication.
- The findings indicate that while destroying mtDNA might benefit some herpesviruses, it is not necessary for the replication of HSV-1 in cell culture.
Article Synopsis
- Herpes simplex virus 1 (HSV-1) causes the rapid removal of mitochondrial DNA (mtDNA) in infected cells, which is influenced by a viral protein called UL12.5.
- While it was initially thought that UL12.5 itself degraded mtDNA through its own nuclease activity, new findings reveal that this activity is not necessary for mtDNA loss.
- Instead, cellular nucleases like endonuclease G (ENDOG) and endonuclease G-like 1 (EXOG) are essential in facilitating the mtDNA depletion triggered by UL12.5, emphasizing their significance in maintaining mtDNA stability.
Article Synopsis
- - The herpes simplex virus type 1 (HSV-1) gene UL12 produces two different mRNAs that code for related proteins: full-length UL12, which is found in the nucleus and is involved in producing mature viral genomes, and UL12.5, a truncated version that acts in mitochondria to degrade mitochondrial DNA.
- - The study identified specific regions responsible for the subcellular localization of these proteins, highlighting that the amino-terminal region of UL12 is crucial for its nuclear targeting, while a specific sequence in UL12.5 helps it localize to the mitochondria.
- - UL12.5 not only shows mitochondrial localization characteristics similar to matrix proteins but also requires its exonuclease activity to effectively eliminate mitochondrial