Phosphonoacid prodrugs with greatly increased antiviral activity in HCMV-infected cells, in vitro

1995 ◽  
Vol 26 (3) ◽  
pp. A294 ◽  
Keyword(s):  
Antiviral Activity ◽  
Infected Cells

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.

Lipid prodrugs of phosphonoacids: greatly enhanced antiviral activity of 1-O-octadecyl-sn-glycero-3-phosphonoformate in HIV-1, HSV-1 and HCMV-infected cells, in vitro

1996 ◽  
Vol 31 (1-2) ◽  
pp. 59-67 ◽  
Author(s):  
Karl Y. Hostetler ◽  
Ganesh D. Kini ◽  
James R. Beadle ◽  
Kathy A. Aldern ◽  
Michael F. Gardner ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Infected Cells ◽  
Hiv 1 ◽  
Hsv 1

scholarly journals In vitro evaluation of antiviral efficacy of a Siddha Formulation against SARS-CoV-2

2021 ◽  
Author(s):  
Divya Kanchibhotla ◽  
Jeetu Pathak ◽  
Hari Venkatesh K.R. ◽  
Ravi reddy ◽  
Monika Pathania
Keyword(s):  
Antiviral Activity ◽  
Healthcare Systems ◽  
Positive Control ◽  
Epithelial Cell Line ◽  
Viral Isolate ◽  
Antiviral Efficacy ◽  
Kidney Epithelial Cell ◽  
Kidney Epithelial Cell Line ◽  
Infected Cells

Abstract Introduction: SARS-CoV-2 virus caused COVID-19 pandemic with 218 million cases and 45 million deaths world over. It has challenged the already overburdened healthcare systems and created an urgent need to investigate solutions present in other healthcare systems. In this study Kabasura Kudineer is investigated as an intervention to influence the immune response which is beneficial for the host and stop the viral replication. Methods: Kabasura Kudineer is a polyherbal formulation containing 15 herbal drugs mixed in equal quantity. It is an official Siddha formulation, used for phlegmatic fevers and flu-like symptoms. To conduct this study Vero E6 (CL1008), the African monkey kidney epithelial cell line was taken and infected with SARS-CoV-2 viral isolate. The Kabasura Kudineer was added in different concentrations; 0.5 mg/mL, 0.25 mg/mL, 0.12 mg/mL, 0.06 mg/mL and 0.03 mg/mL to the infected cells respectively. These cell plates were incubated for 3 days in 5% CO2 incubator. Remdesivir was used as a positive control. The cells were fixed with formaldehyde, stained with crystal violet and plaques were visualised. Plaques were counted as PFU/ml. Result: Kabasura Kudineer was found to exhibit good antiviral activity against SARS-CoV-2. The highest antiviral activity was 81.5% at a concentration of 0.5 mg/ml. The IC-50 value was found to be 0.2 mg/mL. Conclusion: The antiviral efficacy of Kabasura Kudineer in our study showed reduction in the viral load which supports the results of clinical studies. Kabasura Kudineer can be used widely in a clinical setting as a treatment for COVID-19.

scholarly journals Heme Oxygenase-1 Exerts Antiviral Activity against Hepatitis A Virus In Vitro

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1229
Author(s):  
Dong-Hwi Kim ◽  
Hee-Seop Ahn ◽  
Hyeon-Jeong Go ◽  
Da-Yoon Kim ◽  
Jae-Hyeong Kim ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Protein Expression ◽  
Heme Oxygenase ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Health Concern ◽  
Heme Oxygenase 1 ◽  
Infected Cells ◽  
In Cells

Hepatitis A virus (HAV), the causative pathogen of hepatitis A, induces severe acute liver injuries in humans and is a serious public health concern worldwide. However, appropriate therapeutics have not yet been developed. The enzyme heme oxygenase-1 (HO-1) exerts antiviral activities in cells infected with several viruses including hepatitis B and C viruses. In this study, we demonstrated for the first time the suppression of virus replication by HO-1 in cells infected with HAV. Hemin (HO-1 inducer) induced HO-1 mRNA and protein expression, as expected, and below 50 mM, dose-dependently reduced the viral RNA and proteins in the HAV-infected cells without cytotoxicity. Additionally, HO-1 protein overexpression using a protein expression vector suppressed HAV replication. Although ZnPP-9, an HO-1 inhibitor, did not affect HAV replication, it significantly inhibited hemin-induced antiviral activity in HAV-infected cells. Additionally, FeCl3, CORM-3, biliverdin, and the HO-1 inducers andrographolide and CoPP inhibited HAV replication in the HAV-infected cells; andrographolide and CoPP exhibited a dose-dependent effect. In conclusion, these results suggest that HO-1 effectively suppresses HAV infection in vitro, and its enzymatic products appear to exert antiviral activity. We expect that these results could contribute to the development of a new antiviral drug for HAV.

scholarly journals Strigolactone Analogs Are Promising Antiviral Agents for the Treatment of Human Cytomegalovirus Infection

2020 ◽  
Vol 8 (5) ◽  
pp. 703
Author(s):  
Matteo Biolatti ◽  
Marco Blangetti ◽  
Giulia D’Arrigo ◽  
Francesca Spyrakis ◽  
Paola Cappello ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Human Cytomegalovirus ◽  
Antiviral Agents ◽  
Nucleoside Analogs ◽  
Developed Countries ◽  
Promising Alternative ◽  
Late Protein ◽  
Potential Applications ◽  
Infected Cells

The human cytomegalovirus (HCMV) is a widespread pathogen and is associated with severe diseases in immunocompromised individuals. Moreover, HCMV infection is the most frequent cause of congenital malformation in developed countries. Although nucleoside analogs have been successfully employed against HCMV, their use is hampered by the occurrence of serious side effects. There is thus an urgent clinical need for less toxic, but highly effective, antiviral drugs. Strigolactones (SLs) are a novel class of plant hormones with a multifaceted activity. While their role in plant-related fields has been extensively explored, their effects on human cells and their potential applications in medicine are far from being fully exploited. In particular, their antiviral activity has never been investigated. In the present study, a panel of SL analogs has been assessed for antiviral activity against HCMV. We demonstrate that TH-EGO and EDOT-EGO significantly inhibit HCMV replication in vitro, impairing late protein expression. Moreover, we show that the SL-dependent induction of apoptosis in HCMV-infected cells is a contributing mechanism to SL antiviral properties. Overall, our results indicate that SLs may be a promising alternative to nucleoside analogs for the treatment of HCMV infections.

scholarly journals Extracellular 2′-5′ Oligoadenylate Synthetase Stimulates RNase L-Independent Antiviral Activity: a Novel Mechanism of Virus-Induced Innate Immunity

2010 ◽  
Vol 84 (22) ◽  
pp. 11898-11904 ◽  
Author(s):  
Helle Kristiansen ◽  
Christina A. Scherer ◽  
Maralee McVean ◽  
Shawn P. Iadonato ◽  
Susanne Vends ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Antiviral Agent ◽  
Rnase L ◽  
Oligoadenylate Synthetase ◽  
Antiviral Compound ◽  
Clinical Prognosis ◽  
Strong Antiviral Activity ◽  
Infected Cells

ABSTRACT The 2′-5′ oligoadenylate synthetase (OAS) proteins are traditionally considered intracellular antiviral proteins. However, several studies demonstrate a correlation between the concentration of freely circulating OAS protein in sera from hepatitis C patients and their clinical prognosis. Here we demonstrate that extracellular OAS1 enters into cells and possesses a strong antiviral activity, both in vitro and in vivo, which is independent of RNase L. The OAS protein directly inhibits viral proliferation and does not require the activation of known antiviral signaling pathways. We propose that OAS produced by cells infected with viruses is released to the extracellular space, where it acts as a paracrine antiviral agent. Thus, the OAS protein represents the first direct antiviral compound released by virus-infected cells.

scholarly journals Synthesis and Screening of Anti-HSV-1 Activity of Thioglucoside Derivatives of Natural Polyhydroxy-1,4-Naphthoquinones

2019 ◽  
Vol 14 (6) ◽  
pp. 1934578X1986067 ◽  
Author(s):  
Sergey G. Polonik ◽  
Natalia V. Krylova ◽  
Galina G. Kompanets ◽  
Olga V. Iunikhina ◽  
Yuri E. Sabutski
Keyword(s):  
Antiviral Activity ◽  
Radical Scavenging ◽  
Effective Inhibition ◽  
Infected Cells ◽  
Virucidal Effect ◽  
Simplex Virus ◽  
Derivatives Of ◽  
Hsv 1

Four 1,4-naphthoquinone dithioglucoside derivatives based on natural polyhydroxy-1,4-naphthoquinones were synthesized. These thioglucosides were screened for their antiradical and antiviral activity in vitro. Antiradical activity of tested compounds was determined by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. The anti-herpes simplex virus type 1 (anti-HSV-1) activity of thioglucosides was analyzed by the cytopathic effect inhibition assay and mode of antiviral action was determined by the addition of the tested compounds to uninfected cells, to the virus prior to infection, or to herpes-infected cells. Most effective inhibition of HSV-1 replication was observed at pretreatment of virus by the compounds (direct virucidal effect). The dithioglucoside conjugate with the single β-OH group and lipophilic ethyl substituent in naphthoquinone core showed the greatest antiviral activity.

scholarly journals ANTIVIRAL ACTIVITY OF PHOSPRENYL AND GAMAPREN AGAINST INFECTION CAUSED BY INFLUENZA A (H5N1) VIRUS IN CELL CULTURE

2017 ◽  
Vol 62 (4) ◽  
pp. 168-173
Author(s):  
A. V. Sanin ◽  
P. G. Deryabin ◽  
A. N. Narovlyansky ◽  
A. V. Pronin ◽  
T. N. Kozhevnikova
Keyword(s):  
Cell Culture ◽  
Antiviral Activity ◽  
Influenza A ◽  
H5n1 Virus ◽  
Antiviral Effect ◽  
Significant Inhibition ◽  
Infected Cells ◽  
Cytopathogenic Effect ◽  
Higher Doses

The antiviral activity of Phosprenyl and Gamapren in vitro against highly pathogenic strain of avian influenza H5N1 virus was studied. Inoculation of the virus to the susceptible cell culture led to development of the cytopathogenic effect. Preliminary introduction of Phosprenyl and Gamapren an hour prior to infecting the cells with virus 10.0 TCID50 dose completely inhibited the cytopathogenic activity of the virus. At higher doses of virus (100.0 TCID50) significant inhibition of the infectious activity of the virus was observed: 70% of infected cells survived under the action of Phosprenyl, and 90% under the action of Gamapren. With the introduction of the preparations simultaneously with the infection of cells with virus at a dose of 10.0 TCID50 virtually 100% of infected cells survived, while in control cultures death of 100% of the cells occurred. After infection with the virus at a dose of 100.0 TCID50 Phosprenyl and Gamapren caused 50% protection of the cells. The antiviral effect of the drugs Phosprenyl and Gamapren may be associated not only with their virulicidal, but with anti-viral activity as well.

scholarly journals Chloroquine inhibits Zika Virus infection in different cellular models

2016 ◽  
Author(s):  
Rodrigo Delvecchio ◽  
Luiza M Higa ◽  
Paula Pezzuto ◽  
Ana Luiza Valadão ◽  
Patrícia P Garcez ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Zika Virus ◽  
Antiviral Agents ◽  
Virus Production ◽  
Congenital Defects ◽  
Zikv Infection ◽  
Cytotoxic Effects ◽  
Cellular Models ◽  
Infected Cells

SummaryZika virus (ZIKV) infectionin uteromight lead to microcephaly and other congenital defects. In adults, cases of Guillain-Barré syndrome and meningoencephalitis associated with ZIKV infection have been reported, and no specific therapy is available so far. There is urgency for the discovery of antiviral agents capable of inhibiting viral replication and its deleterious effects. Chloroquine is widely administered as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in VERO, human brain microvascular endothelial, and neural stem cells. We demonstratedin vitrothat chloroquine reduces the number of ZIKV-infected cells, virus production and cell death promoted by ZIKV infection without cytotoxic effects. Our results suggest that chloroquine is a promising candidate for ZIKV clinical trials, since it is already approved for clinical use and can be safely administered to pregnant woman.

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