scholarly journals Inhibition of Enterovirus 71 by Picochlorum sp. 122 via AKT and ATM/ATR Signaling Pathways

2021 ◽  
Author(s):  
Min Guo ◽  
Ruilin Zheng ◽  
Hua-lian Wu ◽  
Danyang Chen ◽  
Jingyao Su ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Signaling Pathways ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Vero Cells ◽  
Host Cells ◽  
Global Public Health ◽  
Protein Levels

Abstract Enterovirus 71 (EV71) pose a critical threat in global public health and may lead to severe and even lethal cases of hand-foot-and-mouth disease (HFMD). No effective antiviral agents are available to the masses for treatment of HFMD caused by EV71. Polysaccharide provides a good clinical application for antivirus. Polysaccharides extracted from Picochlorum sp. 122 (PPE) is a kind of seaweed Polysaccharides, the reports on its antiviral activity are limited. In this study, the antiviral activity was verified in Vero cells. Briefly, PPE has been demonstrated to restrain EV71 infection through MTT assay and cellular cytopathic effect. In addition, the decrease of the nucleic acid and protein levels of VP1 indicated PPE effectively inhibited the proliferation of EV71 in Vero cells. Furthermore, the annexinV-affinity assay suggested that PPE protected host cells from apoptosis. The mechanistic investigations revealed that PPE restrained EV71-induced host-cells apoptosis by AKT and ATM/ATR signaling pathways. In conclusion, these results demonstrate PPE is a hopeful antiviral drug for the infection of EV71.

scholarly journals Antidepressant Sertraline is a Broad-Spectrum Inhibitor of Enteroviruses Targeting Viral Entry Through Neutralization of Endolysosomal Acidification

2021 ◽  
Author(s):  
Kuan-Chi Tseng ◽  
Bang-Yan Hsu ◽  
Pin Ling ◽  
Wen-Wen Lu ◽  
Cheng-Wen Lin ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Entry ◽  
Broad Spectrum ◽  
Culture Media ◽  
Antiviral Drug ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Antiviral Effect ◽  
Neurological Complications ◽  
Low Ph

Enterovirus 71 (EV71) is an etiological agent of hand foot and mouth disease and can also cause neurological complications in young children. However, there are no approved drugs to treat EV71 infections. In this study, we conducted an antiviral drug screening by using a Food and Drug Administration (FDA)-approved drug library. We identified five drugs that showed dose-dependent inhibition of viral replication. Sertraline was further characterized because it exhibited the most potent antiviral activity with the highest selectivity index among the five hits. The antiviral activity of sertraline was noted for other EV serotypes. The drug’s antiviral effect is not likely associated with its approved indications as an antidepressant and its mode-of-action as a selective serotonin reuptake inhibitor. The time-of-addition assay revealed that sertraline inhibited an EV71 infection at the entry stage. We also showed that sertraline partitioned into acidic compartments, such as endolysosomes, to neutralize the low pH levels. In agreement with the findings, the antiviral effect of sertraline could be relieved greatly by exposing virus-infected cells to extracellular low-pH culture media. Together, we have identified an FDA-approved antidepressant with the new indication for the broad-spectrum EV inhibition by blocking viral entry through the alkalization of the endolysosomal route.

scholarly journals Peptidyl Aldehyde NK-1.8k Suppresses Enterovirus 71 and Enterovirus 68 Infection by Targeting Protease 3C

2015 ◽  
Vol 59 (5) ◽  
pp. 2636-2646 ◽  
Author(s):  
Yaxin Wang ◽  
Ben Yang ◽  
Yangyang Zhai ◽  
Zheng Yin ◽  
Yuna Sun ◽  
...  
Keyword(s):  
Antiviral Drug ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Binding Pocket ◽  
The United States ◽  
Single Amino Acid ◽  
Global Public Health ◽  
Causative Agents ◽  
Low Cytotoxicity ◽  
Neurological Infections

ABSTRACTEnterovirus (EV) is one of the major causative agents of hand, foot, and mouth disease in the Pacific-Asia region. In particular, EV71 causes severe central nervous system infections, and the fatality rates from EV71 infection are high. Moreover, an outbreak of respiratory illnesses caused by an emerging EV, EV68, recently occurred among over 1,000 young children in the United States and was also associated with neurological infections. Although enterovirus has emerged as a considerable global public health threat, no antiviral drug for clinical use is available. In the present work, we screened our compound library for agents targeting viral protease and identified a peptidyl aldehyde, NK-1.8k, that inhibits the proliferation of different EV71 strains and one EV68 strain and that had a 50% effective concentration of 90 nM. Low cytotoxicity (50% cytotoxic concentration, >200 μM) indicated a high selective index of over 2,000. We further characterized a single amino acid substitution inside protease 3C (3Cpro), N69S, which conferred EV71 resistance to NK-1.8k, possibly by increasing the flexibility of the substrate binding pocket of 3Cpro. The combination of NK-1.8k and an EV71 RNA-dependent RNA polymerase inhibitor or entry inhibitor exhibited a strong synergistic anti-EV71 effect. Our findings suggest that NK-1.8k could potentially be developed for anti-EV therapy.

scholarly journals Antidepressant Sertraline Is a Broad-Spectrum Inhibitor of Enteroviruses Targeting Viral Entry through Neutralization of Endolysosomal Acidification

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 109
Author(s):  
Kuan-Chi Tseng ◽  
Bang-Yan Hsu ◽  
Pin Ling ◽  
Wen-Wen Lu ◽  
Cheng-Wen Lin ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Entry ◽  
Broad Spectrum ◽  
Culture Media ◽  
Antiviral Drug ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Antiviral Effect ◽  
Neurological Complications ◽  
Low Ph

Enterovirus 71 (EV71) is an etiological agent of hand foot and mouth disease and can also cause neurological complications in young children. However, there are no approved drugs as of yet to treat EV71 infections. In this study, we conducted antiviral drug screening by using a Food and Drug Administration (FDA)-approved drug library. We identified five drugs that showed dose-dependent inhibition of viral replication. Sertraline was further characterized because it exhibited the most potent antiviral activity with the highest selectivity index among the five hits. The antiviral activity of sertraline was noted for other EV serotypes. The drug’s antiviral effect is not likely associated with its approved indications as an antidepressant and its mode-of-action as a selective serotonin reuptake inhibitor. The time-of-addition assay revealed that sertraline inhibited an EV71 infection at the entry stage. We also showed that sertraline partitioned into acidic compartments, such as endolysosomes, to neutralize the low pH levels. In agreement with the findings, the antiviral effect of sertraline could be greatly relieved by exposing virus-infected cells to extracellular low-pH culture media. Ultimately, we have identified a use for an FDA-approved antidepressant in broad-spectrum EV inhibition by blocking viral entry through the alkalization of the endolysosomal route.

scholarly journals Antiviral activity of silymarin and baicalein against dengue virus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhao Xuan Low ◽  
Brian Ming OuYong ◽  
Pouya Hassandarvish ◽  
Chit Laa Poh ◽  
Babu Ramanathan
Keyword(s):  
Antiviral Activity ◽  
Dengue Virus ◽  
Viral Entry ◽  
Dengue Infection ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Vero Cells ◽  
Viral Envelope ◽  
E Protein

AbstractDengue is an arthropod-borne viral disease that has become endemic and a global threat in many countries with no effective antiviral drug available currently. This study showed that flavonoids: silymarin and baicalein could inhibit the dengue virus in vitro and were well tolerated in Vero cells with a half-maximum cytotoxic concentration (CC50) of 749.70 µg/mL and 271.03 µg/mL, respectively. Silymarin and baicalein exerted virucidal effects against DENV-3, with a selective index (SI) of 10.87 and 21.34, respectively. Baicalein showed a better inhibition of intracellular DENV-3 progeny with a SI of 7.82 compared to silymarin. Baicalein effectively blocked DENV-3 attachment (95.59%) to the Vero cells, while silymarin prevented the viral entry (72.46%) into the cells, thus reducing viral infectivity. Both flavonoids showed promising antiviral activity against all four dengue serotypes. The in silico molecular docking showed that silymarin could bind to the viral envelope (E) protein with a binding affinity of − 8.5 kcal/mol and form hydrogen bonds with the amino acids GLN120, TRP229, ASN89, and THR223 of the E protein. Overall, this study showed that silymarin and baicalein exhibited potential anti-DENV activity and could serve as promising antiviral agents for further development against dengue infection.

scholarly journals In Vitro and in Vivo Antiviral Activity of Mizoribine Against Foot-And-Mouth Disease Virus

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1723 ◽  
Author(s):  
Shi-Fang Li ◽  
Mei-Jiao Gong ◽  
Yue-Feng Sun ◽  
Jun-Jun Shao ◽  
Yong-Guang Zhang ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Early Stage ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals, which has significant economic consequences in affected countries. As the currently available vaccines against FMD provide no protection until 4–7 days post-vaccination, the only alternative method to control the spread of FMD virus (FMDV) during outbreaks is the application of antiviral agents. Hence, it is important to identify effective antiviral agents against FMDV infection. In this study, we found that mizoribine has potent antiviral activity against FMDV replication in IBRS-2 cells. A time-of-drug-addition assay demonstrated that mizoribine functions at the early stage of replication. Moreover, mizoribine also showed antiviral effect on FMDV in vivo. In summary, these results revealed that mizoribine could be a potential antiviral drug against FMDV.

scholarly journals Nitrogen-Based Heterocyclic Compounds: A Promising Class of Antiviral Agents against Chikungunya Virus

Life ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 16
Author(s):  
Andreza C. Santana ◽  
Ronaldo C. Silva Filho ◽  
José C. J. M. D. S. Menezes ◽  
Diego Allonso ◽  
Vinícius R. Campos
Keyword(s):  
Antiviral Activity ◽  
Mechanism Of Action ◽  
Heterocyclic Compounds ◽  
Chikungunya Virus ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Important Class ◽  
Available Nitrogen ◽  
Global Threat ◽  
Present Understanding

Arboviruses, in general, are a global threat due to their morbidity and mortality, which results in an important social and economic impact. Chikungunya virus (CHIKV), one of the most relevant arbovirus currently known, is a re-emergent virus that causes a disease named chikungunya fever, characterized by a severe arthralgia (joint pains) that can persist for several months or years in some individuals. Until now, no vaccine or specific antiviral drug is commercially available. Nitrogen heterocyclic scaffolds are found in medications, such as aristeromycin, favipiravir, fluorouracil, 6-azauridine, thioguanine, pyrimethamine, among others. New families of natural and synthetic nitrogen analogous compounds are reported to have significant anti-CHIKV effects. In the present work, we focus on these nitrogen-based heterocyclic compounds as an important class with CHIKV antiviral activity. We summarize the present understanding on this class of compounds against CHIKV and also present their possible mechanism of action.

scholarly journals Flavonol 7-O-Glucoside Herbacitrin Inhibits HIV-1 Replication through Simultaneous Integrase and Reverse Transcriptase Inhibition

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Éva Áy ◽  
Attila Hunyadi ◽  
Mária Mezei ◽  
János Minárovits ◽  
Judit Hohmann
Keyword(s):  
Antiviral Activity ◽  
Reverse Transcriptase ◽  
Cell Cultures ◽  
Core Protein ◽  
Integrase Inhibitor ◽  
Host Cells ◽  
Cytotoxic Activities ◽  
Protein Levels ◽  
Hiv 1 ◽  
Antiretroviral Activity

Here we report the evaluation of the antiretroviral effect of two flavonoid 7-O-glucosides, herbacitrin (1) and gossypitrin (2), together with quercetin (3), a well-studied flavonol. Antiviral activity of the flavonoids was assessed by analyzing HIV-1 p24 core protein levels in the supernatants of HIV-1 infected MT-4 and MT-2 cell cultures. The compounds showed mild to weak cytotoxic activities on the host cells; herbacitrin was the strongest in this regard (CC50=27.8 and 63.64 μM on MT-4 and MT-2 cells, respectively). In nontoxic concentrations, herbacitrin and quercetin reduced HIV-1 replication, whereas gossypitrin was ineffective. Herbacitrin was found to inhibit reverse transcriptase at 21.5 μM, while it was a more potent integrase inhibitor already active at 2.15 μM. Therefore, our observations suggest that herbacitrin exerts antiretroviral activity through simultaneously acting on these two targets of HIV-1 and that integrase inhibition might play a major role in this activity.

scholarly journals Ability of Foot-and-Mouth Disease Virus To Form Plaques in Cell Culture Is Associated with Suppression of Alpha/Beta Interferon

1999 ◽  
Vol 73 (12) ◽  
pp. 9891-9898 ◽  
Author(s):  
Jarasvech Chinsangaram ◽  
Maria E. Piccone ◽  
Marvin J. Grubman
Keyword(s):  
Antiviral Activity ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Host Cells ◽  
Wild Type Virus ◽  
Beta Interferon ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Alpha Beta

ABSTRACT A genetic variant of foot-and-mouth disease virus lacking the leader proteinase coding region (A12-LLV2) is attenuated in both cattle and swine and, in contrast to wild-type virus (A12-IC), does not spread from the initial site of infection after aerosol exposure of bovines. We have identified secondary cells from susceptible animals, i.e., bovine, ovine, and porcine animals, in which infection with A12-LLV2, in contrast to A12-IC infection, does not produce plaques; this result indicates that this virus cannot spread from the site of initial infection to neighboring cells. Nevertheless, A12-LLV2 can infect these cells, but cytopathic effects and virus yields are significantly reduced compared to those seen with A12-IC infection. Reverse transcription-PCR analysis demonstrates that both A12-LLV2 and A12-IC induce the production of alpha/beta interferon (IFN-α/β) mRNA in host cells. However, only supernatants from A12-LLV2-infected cells have significant antiviral activity. The antiviral activity in supernatants from A12-LLV2-infected embryonic bovine kidney cells is IFN-α/β specific, as assayed with mouse embryonic fibroblast cells with or without IFN-α/β receptors. The results obtained with cell cultures demonstrate that the ability of A12-IC to form plaques is associated with the suppression of IFN-α/β expression and suggest a role for this host factor in the inability of A12-LLV2 to spread and cause disease in susceptible animals.

scholarly journals Infection of SCID mice with Montana Myotis leukoencephalitis virus as a model for flavivirus encephalitis

2002 ◽  
Vol 83 (8) ◽  
pp. 1887-1896 ◽  
Author(s):  
Nathalie Charlier ◽  
Pieter Leyssen ◽  
Jan Paeshuyse ◽  
Christian Drosten ◽  
Herbert Schmitz ◽  
...  
Keyword(s):  
Yellow Fever Virus ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Vero Cells ◽  
Scid Mice ◽  
Fever Virus ◽  
Viral Rna ◽  
Interferon Α ◽  
Immunocompetent Mice ◽  
Antiviral Targets

We have established a convenient animal model for flavivirus encephalitis using Montana Myotis leukoencephalitis virus (MMLV), a bat flavivirus. This virus has the same genomic organization, and contains the same conserved motifs in genes that encode potential antiviral targets, as flaviviruses that cause disease in man (N. Charlier et al., accompanying paper), and has a similar particle size (approximately 40 nm). MMLV replicates well in Vero cells and appears to be equally as sensitive as yellow fever virus and dengue fever virus to a selection of experimental antiviral agents. Cells infected with MMLV show dilation of the endoplasmic reticulum, a characteristic of flavivirus infection. Intraperitoneal, intranasal or direct intracerebral inoculation of SCID mice with MMLV resulted in encephalitis ultimately leading to death, whereas immunocompetent mice were refractory to either intranasal or intraperitoneal infection with MMLV. Viral RNA and/or antigens were detected in the brain and serum of MMLV-infected SCID mice, but not in any other organ examined: MMLV was detected in the olfactory lobes, the cerebral cortex, the limbic structures, the midbrain, cerebellum and medulla oblongata. Infection was confined to neurons. Treatment with the interferon-α/β inducer poly(I)·poly(C) protected SCID mice against MMLV-induced morbidity and mortality, and this protection correlated with a reduction in infectious virus titre and viral RNA load. This validates the MMLV model for use in antiviral drug studies. The MMLV SCID model may, therefore, be attractive for the study of chemoprophylactic or chemotherapeutic strategies against flavivirus infections causing encephalitis.

scholarly journals A silkworm–baculovirus model for assessing the therapeutic effects of antiviral compounds: characterization and application to the isolation of antivirals from traditional medicines

2008 ◽  
Vol 89 (1) ◽  
pp. 188-194 ◽  
Author(s):  
Yutaka Orihara ◽  
Hiroshi Hamamoto ◽  
Hiroshi Kasuga ◽  
Toru Shimada ◽  
Yasushi Kawaguchi ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Vero Cells ◽  
Infection Model ◽  
Nuclear Magnetic Resonance Analysis ◽  
Therapeutic Effects ◽  
Traditional Medicines ◽  
Baculovirus Infection ◽  
Simplex Virus

Ganciclovir, foscarnet, vidarabine and ribavirin, which are used to treat viral infections in humans, inhibited the proliferation of a baculovirus (Bombyx mori nucleopolyhedrovirus) in BmN4 cells, a cultured silkworm cell line. These antiviral agents inhibited the proliferation of baculovirus in silkworm body fluid and had therapeutic effects. Using the silkworm infection model, the antiviral activity of Kampo medicines was screened and it was found that cinnamon bark, a component of the traditional Japanese medicine Mao-to, had a therapeutic effect. Based on the therapeutic activity, the antiviral substance was purified. Nuclear magnetic resonance analysis of the purified fraction revealed that the antiviral activity was due to cinnzeylanine, which has previously been isolated from Cinnamomum zeylanicum. Cinnzeylanine inhibits the proliferation of herpes simplex virus type 1 in Vero cells. These results suggest that the silkworm–baculovirus infection model is useful for screening antiviral agents that are effective for treating humans infected with DNA viruses.

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