3-Hydroxyphthaloyl β-Lactoglobulin. IV. Antiviral Activity in the Mouse Model of Genital Herpesvirus Infection

1998 ◽  
Vol 9 (4) ◽  
pp. 69-79 ◽  
Author(s):  
H Kokuba ◽  
L Aurelian ◽  
AR Neurath
Keyword(s):  
Antiviral Activity ◽  
Mouse Model ◽  
Major Protein ◽  
Viral Glycoprotein ◽  
Lesion Development ◽  
Simultaneous Exposure ◽  
Virus Shedding ◽  
Prophylactic Measures ◽  
Β Lactoglobulin ◽  
Hsv 1

The spread of sexually transmitted infections caused by herpes simplex virus type 2 (HSV-2) has continued unabated despite educational efforts generated in response to the human immunodeficiency virus (HIV) epidemic. Given the absence of effective vaccines, this indicates the need to develop prophylactic measures such as topical antiviral agents. Chemical modification of bovine β-lactoglobulin (β-LG), the major protein of whey, by hydroxyphthalic anhydride (3HP) led to the generation of a potent HIV-1 inhibitor designated 3HP-β-LG. This agent was shown to also have antiviral activity against HSV-2 and HSV-1 in vitro. Recent studies indicate that 3HP-β-LG binds to HSV-1 virions, which, at least in part, involves the viral glycoprotein gE. Here we show that 3HP-β-LG inhibits HSV-2 infection in the mouse model of genital HSV-2 infection. Simultaneous exposure to HSV-2 and 3HP-β-LG caused a significant decrease in the proportion of infected animals (27% virus shedding, 5% lesion development and 0% fatality for 3HP-β-LG as compared to 80% shedding, 60% lesion development and 53% fatality in micetreated with PBS). The proportion of animals with HSV-2 infection after treatment with β-LG was similar to that in the PBS-treated group. Pretreatment with 3HP-β-LG formulated in a gel, which prolongs the presence of the agent in the vagina, also significantly reduced the proportion of HSV-2-infected mice (5% virus shedding, 5% lesion development and 0% fatality for 3HP-β-LG as compared to 70% shedding, 60% lesion development and 40% fatality in vehicle-treated mice). These differences were significant ( P≤0.0005, 0.002 and 0.008 for shedding, lesion development and fatality, respectively). Virus titres in the minority of mice that developed infection were similar to those in untreated mice. HSV-2 infection was not inhibited by treatment of an ongoing infection, indicating that 3HP-β-LG interferes with the initial infection. These data suggest that 3HP-β-LG may be an efficacious agent for preventing vaginal transmission of genital herpesvirus infections.

3-Hydroxyphthaloyl β-Lactoglobulin. III. Antiviral Activity against Herpesviruses

1998 ◽  
Vol 9 (2) ◽  
pp. 177-184 ◽  
Author(s):  
AR Neurath ◽  
N Strick ◽  
Y-Y Li
Keyword(s):  
Antiviral Agents ◽  
Antiviral Agent ◽  
Major Protein ◽  
Compound I ◽  
Sexually Transmitted ◽  
Prophylactic Measures ◽  
Simplex Virus ◽  
Β Lactoglobulin ◽  
Hiv 1 ◽  
Hsv 1

The spread of sexually transmitted diseases, including human immunodeficiency virus type 1 (HIV-1) and herpesvirus infections, has continued unabated despite educational efforts spearheaded as a response to the HIV-1 epidemic. This suggests the need for prophylactic measures, including the application of topical antiviral agents. Chemical modification of bovine β-lactoglobulin (β-LG), the major protein of whey, by hydroxyphthalic anhydride (3HP) led to the generation of a potent HIV-1 inhibitor (designated 3HP-β-LG) shown to also have activity against herpes simplex virus types 1 and 2 (HSV-1, HSV-2). This report provides more detailed results concerning the anti-herpesvirus activity of 3HP-β-LG, indicating that this compound: (i) inhibited infection by human cytomegalovirus (HCMV), which is known to besexually transmitted; (ii) inactivated the infectivity of both HSV-1 and HSV-2; (iii) inhibited cell-to-cell transmission of HSV-1 and HSV-2; and (iv) bound to HSV-1, HSV-2 and HCMV virus particles and partially inhibited the binding of anti-glycoprotein E (gE) and anti-gC monoclonal antibodies to HSV-1 and HSV-2. The binding of 3HP-β-LG to the herpesviruses under study was inhibited by aggregated human IgG, suggesting that the respective viral Fc receptor is one of the target sites for 3HP-β-LG. In agreement with results on inhibition of HIV-1 infection, 3HP-β-LG appears to be the acid anhydride-modified protein of choice as an antiviral agent against herpesviruses.

Antiviral Activity of a Cloned Peptide RC28 Isolated from the Higher Basidiomycetes Mushroom Rozites caperata in a Mouse Model of HSV-1 Keratitis

2015 ◽  
Vol 17 (9) ◽  
pp. 819-828 ◽  
Author(s):  
Naihong Yan ◽  
Fen He ◽  
Frank F. Piraino ◽  
Haotian Xiang ◽  
Jun Chen ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Mouse Model ◽  
Hsv 1

scholarly journals Phytochemical Characterization of Olea europea Leaf Extracts and Assessment of Their Anti-Microbial and Anti-HSV-1 Activity

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1085
Author(s):  
Ichrak Ben-Amor ◽  
Maria Musarra-Pizzo ◽  
Antonella Smeriglio ◽  
Manuela D’Arrigo ◽  
Rosamaria Pennisi ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Entry ◽  
Antiviral Effect ◽  
Vero Cells ◽  
Biological Properties ◽  
Leaf Extracts ◽  
Gram Positive Bacteria ◽  
Entry Assay ◽  
Olea Europea ◽  
Hsv 1

Owing to the richness of bioactive compounds, Olea europea leaf extracts exhibit a range of health effects. The present research evaluated the antibacterial and antiviral effect of leaf extracts obtained from Olea europea L. var. sativa (OESA) and Olea europea var. sylvestris (OESY) from Tunisia. LC-DAD-ESI-MS analysis allowed the identification of different compounds that contributed to the observed biological properties. Both OESA and OESY were active against Gram-positive bacteria (MIC values between 7.81 and 15.61 μg/mL and between 15.61 and 31.25 μg/mL against Staphylococcus aureus ATCC 6538 for OESY and OESA, respectively). The antiviral activity against the herpes simplex type 1 (HSV-1) was assessed on Vero cells. The results of cell viability indicated that Olea europea leaf extracts were not toxic to cultured Vero cells. The half maximal cytotoxic concentration (CC50) values for OESA and OESY were 0.2 mg/mL and 0.82 mg/mL, respectively. Furthermore, both a plaque reduction assay and viral entry assay were used to demonstrate the antiviral activity. In conclusion, Olea europea leaf extracts demonstrated a bacteriostatic effect, as well as remarkable antiviral activity, which could provide an alternative treatment against resistant strains.

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.

Evaluation of the antiviral potential of the soluble forms of glycoprotein D receptors on ocular herpes caused by HSV-1 and HSV-2 infections in a transgenic mouse model

2019 ◽  
Vol 91 (5) ◽  
pp. 820-828 ◽  
Author(s):  
Yoshikazu Fujimoto ◽  
Shin-ichi Hikita ◽  
Keiko Takeda ◽  
Kinuyo Ozaki ◽  
Hideya Inoue ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Glycoprotein D ◽  
Ocular Herpes ◽  
Hsv 1

scholarly journals The Durability of Vaccine Efficacy against Ocular HSV-1 Infection Using ICP0 Mutants 0∆NLS and 0∆RING Is Lost over Time

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1470
Author(s):  
Daniel J. J. Carr ◽  
Amanda Berube ◽  
Edward Gershburg
Keyword(s):  
Virus Replication ◽  
Vaccine Efficacy ◽  
Post Infection ◽  
Corneal Opacity ◽  
Short Term ◽  
Visual Axis ◽  
Virus Shedding ◽  
Virus Challenge ◽  
Hsv 1

Vaccines to viral pathogens in experimental animal models are often deemed successful if immunization enhances resistance of the host to virus challenge as measured by cumulative survival, reduction in virus replication and spread and/or lessen or eliminate overt tissue pathology. Furthermore, the duration of the protective response against challenge is another important consideration that drives a vaccination regimen. In the current study, we assessed the durability of two related vaccines, 0∆NLS and 0∆RING, against ocular herpes simplex virus type 1 (HSV-1) challenge in mice thirty days (short-term) and one year (long-term) following the vaccine boost. The short-term vaccine efficacy study found the 0∆RING vaccine to be nearly equivalent to the 0∆NLS vaccine in comparison to vehicle-vaccinated mice in terms of controlling virus replication and preserving the visual axis. By comparison, the long-term assessment of the two vaccines found notable differences and less efficacy overall as noted below. Specifically, the results show that in comparison to vehicle-vaccinated mice, the 0∆NLS and 0∆RING vaccinated groups were more resistant in terms of survival and virus shedding following ocular challenge. Moreover, 0∆NLS vaccinated mice also possessed significantly less infectious virus in the peripheral and central nervous systems but not the cornea compared to mice vaccinated with vehicle or 0∆RING which had similar levels. However, all vaccinated groups showed similar levels of blood and lymphatic vessel genesis into the central cornea 30 days post infection. Likewise, corneal opacity was also similar among all groups of vaccinated mice following infection. Functionally, the blink response and visual acuity were 25–50% lower in vaccinated mice 30 days post infection compared to measurements taken prior to infection. The results demonstrate a dichotomy between resistance to infection and functional performance of the visual axis that collectively show an overall loss in vaccine efficacy long-term in comparison to short-term studies in a conventional prime-boost protocol.

Antiviral activity of 1,4-disubstituted-1,2,3-triazoles against HSV-1 in vitro

2021 ◽  
Author(s):  
Daiane J Viegas ◽  
Verônica D da Silva ◽  
Camilla D Buarque ◽  
David C Bloom ◽  
Paula A Abreu
Keyword(s):  
Antiviral Activity ◽  
Hsv 1

scholarly journals Cellular uptake and biological effects of antisense oligodeoxynucleotide analogs targeted to herpes simplex virus.

1996 ◽  
Vol 40 (7) ◽  
pp. 1670-1675 ◽  
Author(s):  
Y Shoji ◽  
J Shimada ◽  
Y Mizushima ◽  
A Iwasawa ◽  
Y Nakamura ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Cellular Uptake ◽  
Biological Effects ◽  
Laser Scanning Microscopy ◽  
Antisense Oligodeoxynucleotide ◽  
Acceptor Site ◽  
Simplex Virus ◽  
Hsv 1

In this study, we synthesized antisense oligodeoxynucleotides (ODNs) with phosphodiester, phosphorothioate (S-ODNs), or methylphosphonate linkages complementary to the splicing acceptor site of immediate-early pre-mRNA 5 of herpes simplex virus type 1 (HSV-1). The antiviral activity of each analog on cytopathic effect in cells infected with HSV-1 or HSV-2 was assessed and compared with the cellular uptake of the analog. We found that antisense S-ODNs showed the most potent antiherpetic activity, with 50% inhibitory concentrations of 5 microM for HSV-1 and 0.25 microM for HSV-2. The antiviral effect of antisense S-ODNs was stronger and longer acting than that of acyclovir. Cell association of S-ODNs was the highest and paralleled antiviral activity. Furthermore, some fluorescein isothiocyanate (FITC)-labeled S-ODNs were recognized in the nuclei in HSV-1 infected cells by confocal laser scanning microscopy. S-ODNs located in the nucleus could access the targeted mRNA, which might be responsible for the antiviral activities. Although our study also showed non-sequence-specific activity, which implies that multiple mechanisms are involved, S-ODNs are a promising novel anti-herpetic agent.

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