Fabrication of acyclovir-loaded flexible membrane vesicles (FMVs): evidence of preclinical efficacy of antiviral activity in murine model of cutaneous HSV-1 infection

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.

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

Viruses ◽

10.3390/v13020196 ◽

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.

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

Antiviral Therapy ◽

10.3851/imp3387 ◽

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

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Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma

Cells ◽

10.3390/cells9030614 ◽

2020 ◽

Vol 9 (3) ◽

pp. 614 ◽

Cited By ~ 3

Author(s):

Hector Perez-Montoyo

Keyword(s):

Cell Death ◽

Clinical Evidence ◽

Therapeutic Potential ◽

Membrane Vesicles ◽

Therapeutic Strategies ◽

Adaptive Mechanism ◽

Aggressive Cancer ◽

Preclinical Efficacy ◽

Catabolic Process ◽

Novel Therapeutic

Autophagy is a multistep catabolic process through which misfolded, aggregated or mutated proteins and damaged organelles are internalized in membrane vesicles called autophagosomes and ultimately fused to lysosomes for degradation of sequestered components. The multistep nature of the process offers multiple regulation points prone to be deregulated and cause different human diseases but also offers multiple targetable points for designing therapeutic strategies. Cancer cells have evolved to use autophagy as an adaptive mechanism to survive under extremely stressful conditions within the tumor microenvironment, but also to increase invasiveness and resistance to anticancer drugs such as chemotherapy. This review collects clinical evidence of autophagy deregulation during cholangiocarcinogenesis together with preclinical reports evaluating compounds that modulate autophagy to induce cholangiocarcinoma (CCA) cell death. Altogether, experimental data suggest an impairment of autophagy during initial steps of CCA development and increased expression of autophagy markers on established tumors and in invasive phenotypes. Preclinical efficacy of autophagy modulators promoting CCA cell death, reducing invasiveness capacity and resensitizing CCA cells to chemotherapy open novel therapeutic avenues to design more specific and efficient strategies to treat this aggressive cancer.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.7.1670 ◽

1996 ◽

Vol 40 (7) ◽

pp. 1670-1675 ◽

Cited By ~ 14

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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Antiherpesvirus Activity of the Combination of 5-iodo-2′-deoxycytidine with methotrexate: An in vitro and in vivo Study

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632029400500501 ◽

1994 ◽

Vol 5 (5) ◽

pp. 283-289

Author(s):

C. Cremonesi ◽

C. Scarpini ◽

R. Bianchi ◽

A. Radaelli ◽

M. Gimelli ◽

...

Keyword(s):

Antiviral Activity ◽

Dihydrofolate Reductase ◽

Reductase Inhibitor ◽

Cellular Viability ◽

Cutaneous Lesions ◽

Guinea Pig Model ◽

Simplex Virus ◽

Hsv 1

We evaluated the in vitro and in vivo antiviral activity of the deoxyribonucleoside analogue 5-iodo-2′-deoxycytidine (IDC) combined with the dihydrofolate reductase inhibitor methotrexate (MTX) on herpes simplex virus types 1 and 2 (HSV-1, HSV-2). The IDC-MTX combination synergistically inhibited HSV-1 and HSV-2 replication in vitro at concentrations that did not reduce cellular viability and was very effective in reducing the severity of cutaneous lesions in the experimental guinea pig model in vivo. The antiviral activity of the IDC-MTX combination in guinea pigs was also compared with that of acyclovir and was demonstrated to be higher.

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Ultrastructure of the Effects of Pyrrolidine-fused Chlorins on the Replication of HSV-1

Microscopy and Microanalysis ◽

10.1017/s1431927608089666 ◽

2008 ◽

Vol 14 (S3) ◽

pp. 137-138

Author(s):

António P.A. Matos ◽

Ana R.N. Santos ◽

Maria F. Caeiro ◽

Maria A.F. Faustino ◽

M.G.P.M.S. Neves ◽

...

Keyword(s):

Antiviral Activity ◽

Antiviral Drugs ◽

Cell Complex ◽

New Drugs ◽

Viral Resistance ◽

Porphyrin Derivatives ◽

Cellular Target ◽

Immunocompromised Hosts ◽

Hsv 1

Currently, only few antiviral drugs of proven effectiveness exist against virus of the Herpesviridae family and viral resistance to these drugs, especially in the immunocompromised hosts, has encouraged research for new drugs. Some porphyrin derivatives revealed a significant antiviral activity against HSV-1 virus. However the cellular target of the porphyrin derivatives in the virus-cell complex remains unknown.

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