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Adenovirus-mediated RNA interference against herpes simplex virus infection in vitro
CONCLUSIONS: Adenovirus-mediated siRNA-targeting gD and gE genes effectively inhibit the replication of the HSV in Vero cells. In addition, these findings indicate that the prophylactic use of siRNA is far more effective at inhibiting HSV replication than the therapeutic use.PMID:34905214 | DOI:10.5603/FHC.a2021.0031
Source: Folia Histochemica et Cytobiologica - December 14, 2021 Category: Cytology Authors: Lin Chen Zhi-Qiang Pan Chang-Bin Zhai Source Type: research

4-Thiofuranoid Glycal: Versatile Glycosyl Donor for the Selective Synthesis of -anomer of 4'-thionucleoside and its biological activities
Curr Med Chem. 2021 Nov 15. doi: 10.2174/0929867328666211115121434. Online ahead of print.ABSTRACTThe first highly diastereoselective synthesis of -anomers of 4'-thionucleosides has been carried out by means of electrophilic glycosidation utilizing 3,5-O-(di-t-butylsilylene) (DTBS)-4-thiofuranoid glycal as a glycosyl donor. The resulting glycosides were transformed into ribo-, 2'-deoxy- and arabinofuranosyl nucleosides through a chemical transformation of the 2'-substituent. The additive Pummerer reaction of the glycal S-oxide gave 1,2-di-O-acetyl-3,5-O-DTBS-4-thioribofuranose. The utility of the DTBS-protected 4-thiori...
Source: Current Medicinal Chemistry - November 16, 2021 Category: Chemistry Authors: Kazuhiro Haraguchi Hiroki Kumamoto Hiromichi Tanaka Source Type: research

Viruses, Vol. 12, Pages 1434: Herpes Simplex Virus Type 1 Clinical Isolates Respond to UL29-Targeted siRNA Swarm Treatment Independent of Their Acyclovir Sensitivity
Poranen Veijo Hukkanen Acyclovir is the drug of choice for the treatment of herpes simplex virus (HSV) infections. Acyclovir-resistant HSV strains may emerge, especially during long-term drug use, and subsequently cause difficult-to-treat exacerbations. Previously, we set up a novel treatment approach, based on enzymatically synthesized pools of siRNAs, or siRNA swarms. These swarms can cover kilobases-long target sequences, reducing the likelihood of resistance to treatment. Swarms targeting the UL29 essential gene of HSV-1 have demonstrated high efficacy against HSV-1 in vitro and in vivo. Here, we assessed the an...
Source: Viruses - December 13, 2020 Category: Virology Authors: Kiira Kalke Jenni Lehtinen Jelena Gnjatovic Liisa M. Lund Marie C. Nyman Henrik Paavilainen Julius Orpana Tuomas Lasanen Fanny Frejborg Alesia A. Levanova Tytti Vuorinen Minna M. Poranen Veijo Hukkanen Tags: Article Source Type: research

Enzymatically synthesized 2′-fluoro-modified Dicer-substrate siRNA swarms against herpes simplex virus demonstrate enhanced antiviral efficacy and low cytotoxicity
Publication date: October 2020Source: Antiviral Research, Volume 182Author(s): Alesia A. Levanova, Kiira M. Kalke, Liisa M. Lund, Nina Sipari, Mohammadreza Sadeghi, Marie C. Nyman, Henrik Paavilainen, Veijo Hukkanen, Minna M. Poranen
Source: Antiviral Therapy - August 27, 2020 Category: Virology Source Type: research

Enzymatically synthesized 2'-fluoro-modified Dicer-substrate siRNA swarms against herpes simplex virus demonstrate enhanced antiviral efficacy and low cytotoxicity
Publication date: Available online 13 August 2020Source: Antiviral ResearchAuthor(s): Alesia A. Levanova, Kiira M. Kalke, Liisa M. Lund, Nina Sipari, Mohammadreza Sadeghi, Marie C. Nyman, Henrik Paavilainen, Veijo Hukkanen, Minna M. Poranen
Source: Antiviral Therapy - August 14, 2020 Category: Virology Source Type: research

Enzymatically synthesized 2'-fluoro-modified Dicer-substrate siRNA swarms against herpes simplex virus demonstrate enhanced antiviral efficacy and low cytotoxicity.
Abstract Chemical modifications of small interfering (si)RNAs are used to enhance their stability and potency, and to reduce possible off-target effects, including immunogenicity. We have earlier introduced highly effective antiviral siRNA swarms against herpes simplex virus (HSV), targeting 653 bp of the essential UL29 viral gene. Here, we report a method for enzymatic production and antiviral use of 2'-fluoro-modified siRNA swarms. Utilizing the RNA-dependent RNA polymerase from bacteriophage phi6, we produced 2'-F-siRNA swarms containing either all or a fraction of modified adenosine, cytidine or uridine residu...
Source: Antiviral Research - August 12, 2020 Category: Virology Authors: Levanova AA, Kalke KM, Lund LM, Sipari N, Sadeghi M, Nyman MC, Paavilainen H, Hukkanen V, Poranen MM Tags: Antiviral Res Source Type: research

Interferon Kappa Is Important for Keratinocyte Host Defense against Herpes Simplex Virus-1.
In this study, we found that IFNκ mRNA expression was induced by addition of recombinant IFNκ and poly (I:C); and its expression level was significantly greater than IFNa2, IFNb1, and IFNL1 in both undifferentiated and differentiated normal human epidermal keratinocytes (NHEKs) under resting and stimulation conditions. Although IFNe was expressed at a relatively higher level than other IFNs in resting undifferentiated NHEK, its expression level did not change after stimulation with recombinant IFNκ and poly (I:C). HSV-1 infection inhibited gene expression of IFNκ and IFNe in NHEK. Silencing IFNκ in NHEK led to signifi...
Source: Journal of Immunology Research - May 2, 2020 Category: Allergy & Immunology Tags: J Immunol Res Source Type: research

TRIM21 Aggravates Herpes Simplex Virus Epithelial Keratitis by Attenuating STING-IRF3-Mediated Type I Interferon Signaling
In conclusion, our results have identified that TRIM21 is abnormally high expressed in HSV epithelial keratitis. TRIM21 enhances the replication of HSV-1 in corneal epithelial cells via suppressing the production of type I IFN by inhibiting STING/IRF3 signaling. It also promotes the secretion of IL-6 and TNF-a, thereby aggravating the severity of HSV epithelial keratitis.
Source: Frontiers in Microbiology - April 15, 2020 Category: Microbiology Source Type: research

APX-115A, a pan-NADPH oxidase inhibitor, induces caspase-dependent cell death by suppressing NOX4-ROS signaling in EBV-infected retinal epithelial cells.
Conclusion Taken together, these our results suggest that APX-115A could be a therapeutic agent for treating EBV-infected retinal cells or diseases by inhibiting LMP1-NOX4-ROS signaling. PMID: 31951764 [PubMed - as supplied by publisher]
Source: Current Eye Research - January 16, 2020 Category: Opthalmology Authors: Hong SW, Noh MH, Kim YS, Jin DH, Moon SH, Yang JW, Hur DY Tags: Curr Eye Res Source Type: research

The role of sphingosine-1-phosphate signaling in HSV-1-infected human umbilical vein endothelial cells.
Abstract Infections with the herpes simplex virus type 1 (HSV-1) are common and widespread. Most infections remain undetected but severe forms may develop in newborns and in immunocompromised patients. Moreover, HSV-1 might be involved in the pathogenesis of atherosclerosis, which may include viral infection of the endothelium. Antiviral therapy is efficient to treat symptomatic patients. However, an increasing accumulation of resistance-associated mutations has been observed in the viral genome. Thus, new antiviral strategies are focused on host factors. Among others, signaling of bioactive sphingolipids seems to...
Source: Virus Research - December 6, 2019 Category: Virology Authors: Graber K, Khan F, Glück B, Weigel C, Marzo S, Doshi H, Ehrhardt C, Heller R, Gräler M, Henke A Tags: Virus Res Source Type: research

Current Development of siRNA Bioconjugates: From Research to the Clinic
In this study, it was shown that the main factor determining the nature of the biodistribution of conjugates is their lipophilicity. Conjugates of siRNA with lower lipophilicity; i.e., derivatives of retinoic acid, lithocholic acid, and docosahexanoic acid with greater efficiency than cholesterol conjugates accumulated in the kidneys, bladder, and lungs of the mouse after subcutaneous injection (Biscans et al., 2018). This fact is consistent with previous data that showed that more lipophilic conjugates bind more efficiently to serum components, and thus are not excreted by the kidneys (Wolfrum et al., 2007; Osborn et al.,...
Source: Frontiers in Pharmacology - April 25, 2019 Category: Drugs & Pharmacology Source Type: research

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