scholarly journals Antiviral Activity of the Marine Alga Symphyocladia latiuscula against Herpes Simplex Virus (HSV-1) in Vitro and Its Therapeutic Efficacy against HSV-1 Infection in Mice

2005 ◽  
Vol 28 (12) ◽  
pp. 2258-2262 ◽  
Author(s):  
Hye-Jin Park ◽  
Masahiko Kurokawa ◽  
Kimiyasu Shiraki ◽  
Norio Nakamura ◽  
Jae-Sue Choi ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Therapeutic Efficacy ◽  
Marine Alga ◽  
Simplex Virus ◽  
Hsv 1

scholarly journals Antiviral Activity of the G-Quadruplex Ligand TMPyP4 against Herpes Simplex Virus-1

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 196
Author(s):  
Sara Artusi ◽  
Emanuela Ruggiero ◽  
Matteo Nadai ◽  
Beatrice Tosoni ◽  
Rosalba Perrone ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Dna Replication ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Herpes Simplex Virus 1 ◽  
Tem Analysis ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

The herpes simplex virus 1 (HSV-1) genome is extremely rich in guanine tracts that fold into G-quadruplexes (G4s), nucleic acid secondary structures implicated in key biological functions. Viral G4s were visualized in HSV-1 infected cells, with massive virus cycle-dependent G4-formation peaking during viral DNA replication. Small molecules that specifically interact with G4s have been shown to inhibit HSV-1 DNA replication. We here investigated the antiviral activity of TMPyP4, a porphyrin known to interact with G4s. The analogue TMPyP2, with lower G4 affinity, was used as control. We showed by biophysical analysis that TMPyP4 interacts with HSV-1 G4s, and inhibits polymerase progression in vitro; in infected cells, it displayed good antiviral activity which, however, was independent of inhibition of virus DNA replication or entry. At low TMPyP4 concentration, the virus released by the cells was almost null, while inside the cell virus amounts were at control levels. TEM analysis showed that virus particles were trapped inside cytoplasmatic vesicles, which could not be ascribed to autophagy, as proven by RT-qPCR, western blot, and immunofluorescence analysis. Our data indicate a unique mechanism of action of TMPyP4 against HSV-1, and suggest the unprecedented involvement of currently unknown G4s in viral or antiviral cellular defense pathways.

scholarly journals Cordia americana: Evaluation of in vitro anti-herpes simplex virus activity and in vivo toxicity of leaf extracts

2021 ◽  
pp. 362-368
Author(s):  
Gislaine Franco de Moura- Costa ◽  
Gean Pier Panizzon ◽  
Thalita Zago Oliveira ◽  
Marco Antonio Costa ◽  
João Carlos Palazzo de Mello ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Biological Activities ◽  
Leaf Extracts ◽  
In Vivo Toxicity ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus (HSV) type 1 and type 2 are responsible for causing infections whose symptoms can vary from subclinical to severe manifestations. Cordia americana is a plant used by traditional communities for the treatment of wounds and diarrhoea, as well as infections like flu and syphilis. Scientific evidence has shown that, among other biological activities, the plant possesses antiviral properties; however, the evaluation of the in vivo toxicity of preparations of this plant is still lacking. This study assessed the in vitro anti-HSV-1 and anti-HSV-2 activity of a crude extract (CE) obtained from the leaves of C. americana, as well as its aqueous (FAq) and ethyl-acetate fractions (FAc). In addition, the in vivo toxicity of the FAq was assessed. The sulforhodamine B method was performed to determine the antiviral activity and the in vivo toxicity was evaluated according to Brazilian federal regulations. The CE, FAq, and FAc demonstrated antiviral activity against HSV-1 in vitro, presenting EC50 values of 7.0±1.4, 1.5±0.35, and 7.5±3.8, respectively. The FAq also had activity against HSV-2 with an EC50 of 11.8±1.02. The toxicological study of FAq in animals showed that it had very low toxicity. No death occurred during acute or subchronic experiments, where up to 5000 mg/kg and 150 mg/kg FAq were tested respectively; and there were no signs of toxicity in the subchronic test. The results of this study, in conjunction with further studies, pave the way for a potential topical treatment for skin and mucosal diseases, such as HSV-1 and HSV-2 infections

Inhibition of Herpes Simplex Virus by Polyamines

2009 ◽  
Vol 20 (2) ◽  
pp. 87-98 ◽  
Author(s):  
Ira Yudovin-Farber ◽  
Irina Gurt ◽  
Ronen Hope ◽  
Abraham J Domb ◽  
Ehud Katz
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Clinical Investigation ◽  
Host Cells ◽  
Direct Exposure ◽  
Simplex Virus ◽  
Hsv 1

Background: Herpes simplex virus (HSV) establishes latent infection in humans with periodic reactivation. Acyclovir, valacyclovir and foscarnet are in medical use today against HSV type-1 (HSV-1) and type-2 (HSV-2), inhibiting the DNA synthesis of the viruses. Additional drugs that will affect the growth of these viruses by other mechanisms and also decrease the frequency of appearance of drug-resistant mutants are required. Methods: Cationic polysaccharides were synthesized by conjugation of various oligoamines to oxidized polysaccharides by reductive amination. Polycations of dextran, pullulan and arabinogalactan were grafted with oligoamines of 2–4 amino groups forming Schiff-base imine-based conjugates followed by reduction with borohydride to obtain the stable amine-based conjugate. Evaluation of toxicity to BS-C-1 cells and antiviral activity against HSV-1 and HSV-2 of the different compounds was performed in vitro by a semiquantitative assay. A quantitative study with a selected compound followed. Results: Structure–activity relationship studies showed that the nature of the grafted oligoamine of the polycation plays an essential role in the antiviral activity against HSV-1 and HSV-2. Dextran-propan-1,3-diamine (DPD) was found to be the most potent of all the compounds examined. DPD did not decrease the infectivity of HSV upon direct exposure to the virions. The growth of HSV was significantly inhibited when DPD was added to the host cells 1 h prior to infection, thus preventing the adsorption and penetration of the virus into the cells. Conclusions: Our in vitro data warrant clinical investigation. DPD could have an advantage as a topical application in combination therapy of HSV lesions.

scholarly journals Antiherpesvirus Activities of Two Novel 4′-Thiothymidine Derivatives, KAY-2-41 and KAH-39-149, Are Dependent on Viral and Cellular Thymidine Kinases

2014 ◽  
Vol 58 (8) ◽  
pp. 4328-4340 ◽  
Author(s):  
Natacha Coen ◽  
Sophie Duraffour ◽  
Kazuhiro Haraguchi ◽  
Jan Balzarini ◽  
Joost J. van den Oord ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Epstein Barr Virus ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTThe emergence of drug-resistant herpesviruses represents a significant problem in clinical practice, primarily in immunocompromised patients. Furthermore, effective antiviral therapies against gammaherpesvirus-associated diseases are lacking. Here, we present two thiothymidine derivatives, KAY-2-41 and KAH-39-149, with different spectra of antiviral activity from those of the reference antiherpetic drugs, showing inhibitory activities against herpes simplex virus, varicella-zoster virus (VZV), and particularly against Epstein-Barr virus, with high selectivityin vitro. While KAY-2-41- and KAH-39-149-resistant herpesviruses were found to harbor mutations in the viral thymidine kinase (TK), these mutations conferred only low levels of resistance to these drugs but high levels to other TK-dependent drugs. Also, antiviral assays in HeLa TK-deficient cells showed a lack of KAY-2-41 and KAH-39-149 activities against herpes simplex virus 1 (HSV-1) and HSV-2 TK-deficient mutants. Furthermore, enzymatic TK assays showed the ability of HSV-1 TK, VZV TK, and cellular TK1 and TK2 to recognize and phosphorylate KAY-2-41 and KAH-39-149. These results demonstrate that the compounds depend on both viral and host TKs to exert antiviral activity. Additionally, the antiviral efficacy of KAH-39-149 proved to be superior to that of KAY-2-41 in a mouse model of gammaherpesvirus infection, highlighting the potential of this class of antiviral agents for further development as selective therapeutics against Epstein-Barr virus.

scholarly journals Structural Variability of the Herpes Simplex Virus 1 GenomeIn VitroandIn Vivo

2012 ◽  
Vol 86 (16) ◽  
pp. 8592-8601 ◽  
Author(s):  
Charlotte Mahiet ◽  
Ayla Ergani ◽  
Nicolas Huot ◽  
Nicolas Alende ◽  
Ahmed Azough ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Considerable Proportion ◽  
Inverted Repeats ◽  
Herpes Simplex Virus 1 ◽  
Cell Extracts ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus 1 (HSV-1) is a human pathogen that leads to recurrent facial-oral lesions. Its 152-kb genome is organized in two covalently linked segments, each composed of a unique sequence flanked by inverted repeats. Replication of the HSV-1 genome produces concatemeric molecules in which homologous recombination events occur between the inverted repeats. This mechanism leads to four genome isomers (termed P, IS, IL, and ILS) that differ in the relative orientations of their unique fragments. Molecular combing analysis was performed on DNA extracted from viral particles and BSR, Vero, COS-7, and Neuro-2a cells infected with either strain SC16 or KOS of HSV-1, as well as from tissues of experimentally infected mice. Using fluorescence hybridization, isomers were repeatedly detected and distinguished and were accompanied by a large proportion of noncanonical forms (40%). In both cell and viral-particle extracts, the distributions of the four isomers were statistically equivalent, except for strain KOS grown in Vero and Neuro-2a cells, in which P and IS isomers were significantly overrepresented. In infected cell extracts, concatemeric molecules as long as 10 genome equivalents were detected, among which, strikingly, the isomer distributions were equivalent, suggesting that any such imbalance may occur during encapsidation.In vivo, for strain KOS-infected trigeminal ganglia, an unbalanced distribution distinct from the onein vitrowas observed, along with a considerable proportion of noncanonical assortment.

scholarly journals Entry of Herpes Simplex Virus Type 1 into Primary Sensory Neurons In Vitro Is Mediated by Nectin-1/HveC

2003 ◽  
Vol 77 (5) ◽  
pp. 3307-3311 ◽  
Author(s):  
Sarah M. Richart ◽  
Scott A. Simpson ◽  
Claude Krummenacher ◽  
J. Charles Whitbeck ◽  
Lewis I. Pizer ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Sensory Neurons ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Primary Cultures ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Primary cultures of rat and mouse sensory neurons were used to study the entry of herpes simplex virus type 1 (HSV-1). Soluble, truncated nectin-1 but not HveA prevented viral entry. Antibodies against nectin-1 also blocked infection of rat neurons. These results indicate that nectin-1 is the primary receptor for HSV-1 infection of sensory neurons.

scholarly journals In vitro antiviral activity of antimicrobial peptides against herpes simplex virus 1, adenovirus, and rotavirus

2007 ◽  
Vol 102 (4) ◽  
pp. 469-472 ◽  
Author(s):  
Márcia Cristina Carriel-Gomes ◽  
Jadel Müller Kratz ◽  
Margherita Anna Barracco ◽  
Evelyne Bachére ◽  
Célia Regina Monte Barardi ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Antimicrobial Peptides ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus

Construction and optimization of herpes simplex virus vectors for central nervous system gene delivery based on CRISPR/Cas9-mediated genome editing

2021 ◽  
Vol 21 ◽  
Author(s):  
Xinwei Huang ◽  
Xiuqing Li ◽  
Lijuan Yang ◽  
Pengfei Wang ◽  
Jingyuan Yan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Transgene Expression ◽  
Mouse Hippocampus ◽  
Simplex Virus ◽  
Hsv 1

Aims: We aim to define parameters affecting the safety and long-term transgene expression of attenuated HSV-1 vectors and optimize the expression cassettes to achieve robust and sustained expression in CNS. Background: Engineered, attenuated Herpes simplex virus (HSV) vectors are promising vehicles for gene delivery to the peripheral and central nervous systems. The virus latent promoter (LAP) is commonly used to drive exogenous gene expression; however, parameters affecting the safety and long-term transgene expression of attenuated HSV-1 vectors have not been fully understood. Objective: This study aimed to construct attenuated HSV-1 vectors using the CRISPR-Cas9 system and examine the influence of transgene cassette construction and insertion site on transgene expression and vector safety. Method: In this study, we used a CRISPR-Cas9 system to accurately and efficiently edit attenuated HSV-1 strain 1716, and constructed two series of recombinant virus LMR and LMRx with different sets of gene cassettes insertion in Exon1(LAP2) and 2.0 kb intron downstream of LAP, respectively. The transgene expression and viral gene transcriptional kinetics were compared in in-vitro cell lines. The reporter gene expression and safety profiles of each vector were further evaluated in the mouse hippocampus gene transduction model. Result: The in-vitro cell line analysis indicated that the insertion of a gene expression cassette would disrupt virus gene transcription. Mouse hippocampus transducing analysis suggested that complete expression cassette insertion at 2.0 kb intron could achieve robust and longtime gene expression than the other constructs. Recombinants with gene expression cassettes lacked Poly (A), which induced significant neuronal inflammation due to persistent viral antigen expression and microglia activation. Conclusion: Our results indicated that the integrity of LAT transcripts was not necessary for the establishment of long-term latent expression. Exogenous strong promoters (like cBh promoter) could remain active during latency when placed in Exon1 or 2.0 Kb Intron of LAT locus, although their transcriptional activity declined with time. Consistent with previous research, the foreign gene expression would last much longer when the gene cassette was located downstream of Exon1, which suggested a role of LAP2 in maintaining promoter activity during latency. Besides, over-transcription of the downstream part of LAT may induce continuous activation of the attenuated vectors, suggesting an important role of LAT in maintaining viral reactivation potential.

scholarly journals Antiviral effect of oryzacystatin, a proteinase inhibitor in rice, against herpes simplex virus type 1 in vitro and in vivo.

1995 ◽  
Vol 39 (4) ◽  
pp. 846-849 ◽  
Author(s):  
H Aoki ◽  
T Akaike ◽  
K Abe ◽  
M Kuroda ◽  
S Arai ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Rice Seed ◽  
Simplex Virus ◽  
Hsv 1

Oryzacystatin (OC) is the first-described cystatin originating from rice seed; it consists of two molecular species, OC-I and OC-II, which have antiviral action against poliovirus in vitro (H. Kondo, S. Ijiri, K. Abe, H. Maeda, and S. Arai, FEBS Lett. 299:48-50, 1992). In the experiments reported here, we investigated the effects of OC-I and OC-II on the replication of herpes simplex virus type 1 (HSV-1) in vitro and in vivo. HSV-1 was inoculated onto monolayers of monkey kidney epithelial cells (CV-1 cells) at a multiplicity of infection of 0.1 PFU per cell. After adsorption of the virus onto cells, the cultures were incubated in the presence of either OC-I or OC-II in the concentration range of 1.0 to 300 microM, and the supernatant virus yield was quantitated at 24 h. The effective concentration for 90% inhibition of HSV-1 was 14.8 microM, while a cytotoxic effect on CV-1 cells without infection of HSV-1 was not observed below 500 microM OC-I. Therefore, the apparent in vitro chemotherapeutic index was estimated to be more than 33. In the mouse model of HSV-1-induced keratitis and encephalopathy, topical administration of OC-I to the mouse cornea produced a significant decrease in virus production in the cornea (mean virus yields: 3.11 log10 PFU in the treated group and 4.37 log10 PFU in the control group) and significant improvement in survival rates (P = 0.01). The in vivo antiherpetic effect of OC-I was comparable to that of acyclovir, indicating that topical treatment of HSV-1 infection in humans with OC-I might be possible. Our data also suggest the importance of some thiol proteinases, which may be derived from either the host's cells or HSV-1, during the replication process of HSV-1.

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