Decreased rotavirus infection of MA104 cells via probiotic extract binding to Hsc70 and ß3 integrin receptors

Probiotic bacteria are microorganisms beneficial to human health, useful to improving biological conditions. Thanks to probiotic bacteria the symptoms of viral infections can be alleviated. Different mechanisms whereby probiotic bacteria exert they antiviral effect have been proposed. The aim of this study was to determine whether probiotic bacteria extracts bind to receptors of host cells susceptible of rotavirus (RV) infection. To accomplish this objective, four probiotic bacterial strains of Lactobacillus spp. and Bifidobacterium spp. were tested. Probiotic extracts were obtained after bacterial growth, cell lysis and centrifugation. Obtained probiotic extracts were used in assays to interfere with adhesion and penetration of a RV strain in the mammal cell line MA104. Furthermore, the interaction between probiotic extracts and MA104 cell receptors was evaluated by co-immunoprecipitation assays using anti-ß3-integrins and anti-Hsc70 antibodies. All four probiotic, protein-rich, extracts reduced RV infections in MA104 cells, suggesting a successful antiviral activity mediated by these probiotic extracts. All probiotic extracts significantly exerted thir antiviral activity by interfering with RV adhesion on MA104 cell receptors, with proteins in probiotic extracts competitively interacting with cell surface receptors necessary to RV infection. Co-immunoprecipitation assay results showed that proteins in probiotic extracts were able to bind to ß3-integrinsand Hsc70, which are two cellular receptors required to viral infection. The most significant contribution of this study is an insight into the mechanisms of probiotic antiviral activity, thus expanding current probiotics fundamental knowledge.

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The Interferon-Stimulated Gene IFITM3 Restricts Infection and Pathogenesis of Arthritogenic and Encephalitic Alphaviruses

Journal of Virology ◽

10.1128/jvi.00655-16 ◽

2016 ◽

Vol 90 (19) ◽

pp. 8780-8794 ◽

Cited By ~ 46

Author(s):

Subhajit Poddar ◽

Jennifer L. Hyde ◽

Matthew J. Gorman ◽

Michael Farzan ◽

Michael S. Diamond

Keyword(s):

Viral Infections ◽

Transmembrane Protein ◽

Flow Cytometric Analysis ◽

Antiviral Effect ◽

Host Cells ◽

Type I ◽

Targeted Gene Deletion ◽

Multiple Organs ◽

Viral Burden ◽

Alphavirus Infection

ABSTRACTHost cells respond to viral infections by producing type I interferon (IFN), which induces the expression of hundreds of interferon-stimulated genes (ISGs). Although ISGs mediate a protective state against many pathogens, the antiviral functions of the majority of these genes have not been identified. IFITM3 is a small transmembrane ISG that restricts a broad range of viruses, including orthomyxoviruses, flaviviruses, filoviruses, and coronaviruses. Here, we show that alphavirus infection is increased inIfitm3−/−andIfitmlocus deletion (Ifitm-del) fibroblasts and, reciprocally, reduced in fibroblasts transcomplemented with Ifitm3. Mechanistic studies showed that Ifitm3 did not affect viral binding or entry but inhibited pH-dependent fusion. In a murine model of chikungunya virus arthritis,Ifitm3−/−mice sustained greater joint swelling in the ipsilateral ankle at days 3 and 7 postinfection, and this correlated with higher levels of proinflammatory cytokines and viral burden. Flow cytometric analysis suggested thatIfitm3−/−macrophages from the spleen were infected at greater levels than observed in wild-type (WT) mice, results that were supported by experiments withIfitm3−/−bone marrow-derived macrophages.Ifitm3−/−mice also were more susceptible than WT mice to lethal alphavirus infection with Venezuelan equine encephalitis virus, and this was associated with greater viral burden in multiple organs. Collectively, our data define an antiviral role for Ifitm3 in restricting infection of multiple alphaviruses.IMPORTANCEThe interferon-induced transmembrane protein 3 (IFITM3) inhibits infection of multiple families of viruses in cell culture. Compared to other viruses, much less is known about the antiviral effect of IFITM3 on alphaviruses. In this study, we characterized the antiviral activity of mouse Ifitm3 against arthritogenic and encephalitic alphaviruses using cells and animals with a targeted gene deletion ofIfitm3as well as deficient cells transcomplemented with Ifitm3. Based on extensive virological analysis, we demonstrate greater levels of alphavirus infection and disease pathogenesis when Ifitm3 expression is absent. Our data establish an inhibitory role for Ifitm3 in controlling infection of alphaviruses.

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Antiviral Activity of a Turbot (Scophthalmus maximus) NK-Lysin Peptide by Inhibition of Low-pH Virus-Induced Membrane Fusion

Marine Drugs ◽

10.3390/md17020087 ◽

2019 ◽

Vol 17 (2) ◽

pp. 87 ◽

Cited By ~ 11

Author(s):

Alberto Falco ◽

Regla Medina-Gali ◽

José Poveda ◽

Melissa Bello-Perez ◽

Beatriz Novoa ◽

...

Keyword(s):

Antiviral Activity ◽

Viral Infections ◽

Scophthalmus Maximus ◽

Low Ph ◽

Host Cells ◽

Viral Origin ◽

Membrane Rupture ◽

Viral Particles ◽

Strong Antiviral Activity ◽

Turbot Scophthalmus Maximus

Global health is under attack by increasingly-frequent pandemics of viral origin. Antimicrobial peptides are a valuable tool to combat pathogenic microorganisms. Previous studies from our group have shown that the membrane-lytic region of turbot (Scophthalmus maximus) NK-lysine short peptide (Nkl71–100) exerts an anti-protozoal activity, probably due to membrane rupture. In addition, NK-lysine protein is highly expressed in zebrafish in response to viral infections. In this work several biophysical methods, such as vesicle aggregation, leakage and fluorescence anisotropy, are employed to investigate the interaction of Nkl71–100 with different glycerophospholipid vesicles. At acidic pH, Nkl71–100 preferably interacts with phosphatidylserine (PS), disrupts PS membranes, and allows the content leakage from vesicles. Furthermore, Nkl71–100 exerts strong antiviral activity against spring viremia of carp virus (SVCV) by inhibiting not only the binding of viral particles to host cells, but also the fusion of virus and cell membranes, which requires a low pH context. Such antiviral activity seems to be related to the important role that PS plays in these steps of the replication cycle of SVCV, a feature that is shared by other families of virus-comprising members with health and veterinary relevance. Consequently, Nkl71–100 is shown as a promising broad-spectrum antiviral candidate.

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Papaya Fruit Pulp and Resulting Lactic Fermented Pulp Exert Antiviral Activity against Zika Virus

Microorganisms ◽

10.3390/microorganisms8091257 ◽

2020 ◽

Vol 8 (9) ◽

pp. 1257

Author(s):

Juliano G. Haddad ◽

Victoria Carcauzon ◽

Omar El Kalamouni ◽

Philippe Desprès ◽

Cyrielle Garcia ◽

...

Keyword(s):

Antiviral Activity ◽

Zika Virus ◽

Human Cells ◽

Host Cells ◽

Dependent Manner ◽

Bacterial Strains ◽

Lactic Fermentation ◽

Papaya Pulp ◽

Leuconostoc Pseudomesenteroides

There are a several emerging and re-emerging RNA viruses that are prevalent around the world for which there are no licensed vaccines or antiviral drugs. Zika virus (ZIKV) is an example of an emerging virus that has become a significant concern worldwide because of its association with severe congenital malformations and neurological disorders in adults. Several polyphenol-rich extracts from plants were used as nutraceuticals which exhibit potent in vitro antiviral effects. Here, we demonstrated that the papaya pulp extracted from Carica papaya fruit inhibits the infection of ZIKV in human cells without loss of cell viability. At the non-cytotoxic concentrations, papaya pulp extract has the ability to reduce the virus progeny production in ZIKV-infected human cells by at least 4-log, regardless of viral strains tested. Time-of-drug-addition assays revealed that papaya pulp extract interfered with the attachment of viral particles to the host cells. With a view of preserving the properties of papaya pulp over time, lactic fermentation based on the use of bacterial strains Weissella cibaria 64, Lactobacillus plantarum 75 and Leuconostoc pseudomesenteroides 56 was performed and the resulting fermented papaya pulp samples were tested on ZIKV. We found that lactic fermentation of papaya pulp causes a moderate loss of antiviral activity against ZIKV in a bacterial strain-dependent manner. Whereas IC50 of the papaya pulp extract was 0.3 mg/mL, we found that fermentation resulted in IC50 up to 4 mg/mL. We can conclude that papaya pulp possesses antiviral activity against ZIKV and the fermentation process has a moderate effect on the antiviral effect.

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In Vitro Antiviral Activity of Clove and Ginger Aqueous Extracts against Feline Calicivirus, a Surrogate for Human Norovirus

Journal of Food Protection ◽

10.4315/0362-028x.jfp-15-593 ◽

2016 ◽

Vol 79 (6) ◽

pp. 1001-1012 ◽

Cited By ~ 20

Author(s):

HAMADA A. ABOUBAKR ◽

ANDREW NAUERTZ ◽

NHUNGOC T. LUONG ◽

SHIVANI AGRAWAL ◽

SOBHY A. A. EL-SOHAIMY ◽

...

Keyword(s):

Antiviral Activity ◽

Antiviral Effect ◽

Host Cells ◽

Mass Spectrometry Analysis ◽

Feline Calicivirus ◽

Aqueous Extracts ◽

Human Norovirus ◽

Viral Contamination ◽

Fresh Vegetables ◽

Clove Extract

ABSTRACT Foodborne viruses, particularly human norovirus, are a concern for public health, especially in fresh vegetables and other minimally processed foods that may not undergo sufficient decontamination. It is necessary to explore novel nonthermal techniques for preventing foodborne viral contamination. In this study, aqueous extracts of six raw food materials (flower buds of clove, fenugreek seeds, garlic and onion bulbs, ginger rhizomes, and jalapeño peppers) were tested for antiviral activity against feline calicivirus (FCV) as a surrogate for human norovirus. The antiviral assay was performed using dilutions of the extracts below the maximum nontoxic concentrations of the extracts to the host cells of FCV, Crandell-Reese feline kidney (CRFK) cells. No antiviral effect was seen when the host cells were pretreated with any of the extracts. However, pretreatment of FCV with nondiluted clove and ginger extracts inactivated 6.0 and 2.7 log of the initial titer of the virus, respectively. Also, significant dose-dependent inactivation of FCV was seen when host cells were treated with clove and ginger extracts at the time of infection or postinfection at concentrations equal to or lower than the maximum nontoxic concentrations. By comprehensive two-dimensional gas chromatography–mass spectrometry analysis, eugenol (29.5%) and R-(-)-1,2-propanediol (10.7%) were identified as the major components of clove and ginger extracts, respectively. The antiviral effect of the pure eugenol itself was tested; it showed antiviral activity similar to that of clove extract, albeit at a lower level, which indicates that some other clove extract constituents, along with eugenol, are responsible for inactivation of FCV. These results showed that the aqueous extracts of clove and ginger hold promise for prevention of foodborne viral contamination.

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Inactivation of Herpes Simplex Virus by Photosensitizing Anthraquinones Isolated from Heterophyllaea pustulata

Planta Medica ◽

10.1055/a-1345-6831 ◽

2021 ◽

Author(s):

M. Laura Mugas ◽

Juliana Marioni ◽

Florencia Martinez ◽

Juan J. Aguilar ◽

José L. Cabrera ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Antiviral Activity ◽

Antiviral Effect ◽

Neutral Red ◽

Host Cells ◽

Type I ◽

Antiherpetic Activity ◽

Simplex Virus

Abstract Heterophyllaea pustulata is a phototoxic plant from Argentina. Aerial parts extracts, high in photosensitizing anthraquinones, have shown in vitro antiviral activity. The purpose of this study was to study the antiherpetic activity of the main purified anthraquinones, even evaluating their competence as photodynamic sensitizers to photo-stimulate the antiviral effect. In vitro antiviral activity against Herpes Simplex virus type I and the photo-inactivation of viral particle were studied by the Neutral Red uptake test and observation of the cytopathic effect. Rubiadin 1-methyl ether and 5,5′-bisoranjidiol produced a significant effect (≥ 80% inhibition) with minimal damage to host cells (subtoxic concentration). Anthraquinones with poor antiherpetic activity at its maximum noncytotoxic concentration showed an important photo-stimulated effect, such is the case of soranjidiol and 5,5′-bisoranjidiol (28.0 ± 6.3 vs. 81.8 ± 2.1% and 15.5 ± 0.3 vs. 89.8 ± 1.7%, respectively). The study also proved the decrease of viral particles, necessary to reduce infection. Therefore, photosensitizing anthraquinones from natural resources could be proposed to develop new treatments for localized viral lesions with antimicrobial photodynamic therapy.

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THERAPEUTIC APPLICATIONS OF Spirulina AGAINST HUMAN PATHOGENIC VIRUSES

Journal of Experimental Biology and Agricultural Sciences ◽

10.18006/2021.9(spl-1-gcsgd_2020).s38.s42 ◽

2021 ◽

Vol 9 (Spl-1- GCSGD_2020) ◽

pp. S38-S42

Author(s):

Sharolynne Xiao Tong Liang ◽

◽

Ling Shing Wong ◽

Anto Cordelia Tanislaus Antony Dhanapal ◽

Prakash Balu ◽

...

Keyword(s):

Measles Virus ◽

Therapeutic Agent ◽

Viral Infections ◽

Emerging Infectious Diseases ◽

Antiviral Effect ◽

Food Supplement ◽

Host Cells ◽

Swine Flu ◽

Virus Infections ◽

Enveloped Viruses

Viruses can spread worldwide and the early detection of emerging infectious diseases and outbreaks in humans and animals is important for effective surveillance and prevention. Viruses such as human immunodeficiency virus (HIV), swine flu, and influenza virus are some of the viruses that spread diseases worldwide. However, the non-availability of effective antiviral drugs and the drug-resistance among the virus and host have become the major problems in controlling viral infections. The natural products from microalgae can be an alternative therapeutic agent to control viral infections in humans. Spirulina is a well-known cyanobacterium that has been consumed by humans as a food supplement for more than centuries without side-effects. Spirulina possesses high nutritional values and provides numerous health benefits to the consumers. Spirulina can be an alternative natural therapeutic agent for numerous virus infections as it contains several bioactive compounds with proven antiviral effect on enveloped viruses (Herpes simplex virus, measles virus, mumps virus) and non-enveloped viruses (astrovirus, rotavirus) by preventing the spread of the virus in the host cells. Spirulina also serves as a natural supplement that strengthens the immune system. This review focuses on the antiviral properties and immunostimulant effects of Spirulina as a potential therapeutic supplement on human health.

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Microbiota-independent antiviral protection conferred by aminoglycoside antibiotics

10.1101/248617 ◽

2018 ◽

Cited By ~ 1

Author(s):

Smita Gopinath ◽

Myoungjoo V. Kim ◽

Tasfia Rakib ◽

Patrick W. Wong ◽

Michael van Zandt ◽

...

Keyword(s):

Influenza A ◽

Viral Infections ◽

Antibiotic Use ◽

Antiviral Effect ◽

Aminoglycoside Antibiotics ◽

Host Cells ◽

Vaginal Mucosa ◽

Herpes Simplex Viruses ◽

The Impact

AbstractAntibiotics are widely used to treat infections in humans. However, the impact of antibiotic use on host cells is understudied. We have identified a novel antiviral effect of commonly used aminoglycoside antibiotics. We show that mucosal application of aminoglycosides increased host resistance to a broad range of viral infections including herpes simplex viruses, influenza A virus and Zika virus. Aminoglycoside treatment also reduced viral replication in primary human cells. This antiviral activity was independent of the microbiota as aminoglycoside treatment protected germ-free mice. Microarray analysis uncovered a marked upregulation of transcripts for interferon-stimulated genes (ISGs) following aminoglycoside application. ISG induction was mediated by TLR3, and required TIR-domain-containing adapter-inducing interferon-β (TRIF), signaling adaptor, and interferon regulatory factors 3 (IRF3) and IRF7, transcription factors that promote ISG expression. XCR1+ dendritic cells, which uniquely express TLR3, were recruited to the vaginal mucosa upon aminoglycoside treatment and were required for ISG induction. These results highlight an unexpected ability of aminoglycoside antibiotics to confer broad antiviral resistancein vivo.

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Genome Features and In Vitro Activity against Influenza A and SARS-CoV-2 Viruses of Six Probiotic Strains

BioMed Research International ◽

10.1155/2021/6662027 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Irina V. Soloveva ◽

Tatyana N. Ilyicheva ◽

Vasiliy Yu. Marchenko ◽

Oleg V. Pyankov ◽

Anna G. Tochilina ◽

...

Keyword(s):

Antiviral Activity ◽

Influenza A ◽

Mdck Cells ◽

Bifidobacterium Longum ◽

Bifidobacterium Bifidum ◽

Influenza Viruses ◽

Lactobacillus Fermentum ◽

Probiotic Bacteria ◽

Bacterial Strains

Purpose. The aim of this work was to analyze the complete genome of probiotic bacteria Lactobacillus plantarum 8 RA 3, Lactobacillus fermentum 90 TC-4, Lactobacillus fermentum 39, Bifidobacterium bifidum 791, Bifidobacterium bifidum 1, and Bifidobacterium longum 379 and to test their activity against influenza A and SARS-CoV-2 viruses. Methods. To confirm the taxonomic affiliation of the bacterial strains, MALDI TOF mass spectrometry and biochemical test systems were used. Whole genome sequencing was performed on the Illumina Inc. MiSeq platform. To determine the antiviral activity, A/Lipetsk/1V/2018 (H1N1 pdm09) (EPI_ISL_332798) and A/common gull/Saratov/1676/2018 (H5N6) (EPI_ISL_336925) influenza viruses and SARS-CoV-2 virus strain Australia/VIC01/2020 (GenBank: MT007544.1) were used. Results. All studied probiotic bacteria are nonpathogenic for humans and do not contain the determinants of transmission-type antibiotic resistance and integrated plasmids. Resistance to antibiotics of different classes is explained by the presence of molecular efflux pumps of the MatE and MFS families. Cultures of L. fermentum 90 TC 4, L. plantarum 8 RA 3, and B. bifidum 791 showed a pronounced activity against influenza A viruses in MDCK cells. Activity against the SARS-CoV-2 virus was demonstrated only by the L. fermentum 90 TC 4 strain in VERO cells. Conclusions. The studied probiotic bacteria are safe, have antiviral activity, and are of great importance for the prevention of diseases caused by respiratory viruses that can also infect the human intestine.

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High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication

Viruses ◽

10.3390/v12040442 ◽

2020 ◽

Vol 12 (4) ◽

pp. 442 ◽

Cited By ~ 1

Author(s):

Anna Glanz ◽

Karan Chawla ◽

Stephanie Fabry ◽

Gayatri Subramanian ◽

Julie Garcia ◽

...

Keyword(s):

Antiviral Activity ◽

High Throughput ◽

High Throughput Screening ◽

Transcriptional Activity ◽

Viral Infections ◽

Antiviral Effect ◽

Apoptotic Pathway ◽

Antiviral Genes ◽

Wide Range ◽

Infected Cells

Interferon (IFN) regulatory factor 3 (IRF3) is the key transcription factor for the induction of IFN and antiviral genes. The absence of antiviral genes in IRF3 deficiency leads to susceptibility to a wide range of viral infections. Previously, we uncovered a function for nontranscriptional IRF3 (nt-IRF3), RLR (RIG-I-like receptor)-induced IRF3-mediated pathway of apoptosis (RIPA), which triggers apoptotic killing of virus-infected cells. Using knock-in mice expressing a transcriptionally inactive, but RIPA-active, IRF3 mutant, we demonstrated the relative contribution of RIPA to host antiviral defense. Given that RIPA is a cellular antiviral pathway, we hypothesized that small molecules that promote RIPA in virus-infected cells would act as antiviral agents. To test this, we conducted a high throughput screen of a library of FDA-approved drugs to identify novel RIPA activators. Our screen identified doxorubicin as a potent RIPA-activating agent. In support of our hypothesis, doxorubicin inhibited the replication of vesicular stomatitis virus, a model rhabdovirus, and its antiviral activity depended on its ability to activate IRF3 in RIPA. Surprisingly, doxorubicin inhibited the transcriptional activity of IRF3. The antiviral activity of doxorubicin was expanded to flavivirus and herpesvirus that also activate IRF3. Mechanistically, doxorubicin promoted RIPA by activating the extracellular signal-regulated kinase (ERK) signaling pathway. Finally, we validated these results using another RIPA-activating compound, pyrvinium pamoate, which showed a similar antiviral effect without affecting the transcriptional activity of IRF3. Therefore, we demonstrate that the RIPA branch of IRF3 can be targeted therapeutically to prevent virus infection.

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Antiviral Strategies Using Natural Source-Derived Sulfated Polysaccharides in the Light of the COVID-19 Pandemic and Major Human Pathogenic Viruses

Viruses ◽

10.3390/v14010035 ◽

2021 ◽

Vol 14 (1) ◽

pp. 35

Author(s):

Bimalendu Ray ◽

Imran Ali ◽

Subrata Jana ◽

Shuvam Mukherjee ◽

Saikat Pal ◽

...

Keyword(s):

Antiviral Activity ◽

Viral Infection ◽

Molecular Mechanisms ◽

Viral Infections ◽

Structural Characteristics ◽

Antiviral Agents ◽

Host Cells ◽

Sulfated Polysaccharides ◽

Susceptible Host ◽

Pathogenic Viruses

Only a mere fraction of the huge variety of human pathogenic viruses can be targeted by the currently available spectrum of antiviral drugs. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has highlighted the urgent need for molecules that can be deployed quickly to treat novel, developing or re-emerging viral infections. Sulfated polysaccharides are found on the surfaces of both the susceptible host cells and the majority of human viruses, and thus can play an important role during viral infection. Such polysaccharides widely occurring in natural sources, specifically those converted into sulfated varieties, have already proved to possess a high level and sometimes also broad-spectrum antiviral activity. This antiviral potency can be determined through multifold molecular pathways, which in many cases have low profiles of cytotoxicity. Consequently, several new polysaccharide-derived drugs are currently being investigated in clinical settings. We reviewed the present status of research on sulfated polysaccharide-based antiviral agents, their structural characteristics, structure–activity relationships, and the potential of clinical application. Furthermore, the molecular mechanisms of sulfated polysaccharides involved in viral infection or in antiviral activity, respectively, are discussed, together with a focus on the emerging methodology contributing to polysaccharide-based drug development.

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