Antiviral Activity of the Rhamnolipids Mixture from the Antarctic Bacterium Pseudomonas gessardii M15 against Herpes Simplex Viruses and Coronaviruses

Emerging and re-emerging viruses represent a serious threat to human health at a global level. In particular, enveloped viruses are one of the main causes of viral outbreaks, as recently demonstrated by SARS-CoV-2. An effective strategy to counteract these viruses could be to target the envelope by using surface-active compounds. Rhamnolipids (RLs) are microbial biosurfactants displaying a wide range of bioactivities, such as antibacterial, antifungal and antibiofilm, among others. Being of microbial origin, they are environmentally-friendly, biodegradable, and less toxic than synthetic surfactants. In this work, we explored the antiviral activity of the rhamnolipids mixture (M15RL) produced by the Antarctic bacteria Pseudomonas gessardii M15 against viruses belonging to Coronaviridae and Herpesviridae families. In addition, we investigated the rhamnolipids’ mode of action and the possibility of inactivating viruses on treated surfaces. Our results show complete inactivation of HSV-1 and HSV-2 by M15RLs at 6 µg/mL, and of HCoV-229E and SARS-CoV-2 at 25 and 50 µg/mL, respectively. Concerning activity against HCoV-OC43, 80% inhibition of cytopathic effect was recorded, while no activity against naked Poliovirus Type 1 (PV-1) was detectable, suggesting that the antiviral action is mainly directed towards the envelope. In conclusion, we report a significant activity of M15RL against enveloped viruses and demonstrated for the first time the antiviral effect of rhamnolipids against SARS-CoV-2.

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Na+/K+-ATPase as a Target of Cardiac Glycosides for the Treatment of SARS-CoV-2 Infection

Frontiers in Pharmacology ◽

10.3389/fphar.2021.624704 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kauê Francisco Corrêa Souza e Souza ◽

Bianca Portugal Tavares Moraes ◽

Izabel Christina Nunes de Palmer Paixão ◽

Patrícia Burth ◽

Adriana Ribeiro Silva ◽

...

Keyword(s):

Antiviral Activity ◽

Cell Signaling ◽

Signaling Pathways ◽

Influenza A ◽

Cardiac Glycosides ◽

Antiviral Effect ◽

Cardiac Insufficiency ◽

Α Subunit ◽

Enveloped Viruses ◽

Mortality And Morbidity

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), identified for the first time in Wuhan, China, causes coronavirus disease 2019 (COVID-19), which moved from epidemic status to becoming a pandemic. Since its discovery in December 2019, there have been countless cases of mortality and morbidity due to this virus. Several compounds such as chloroquine, hydroxychloroquine, lopinavir-ritonavir, and remdesivir have been tested as potential therapies; however, no effective treatment is currently recommended by regulatory agencies. Some studies on respiratory non-enveloped viruses such as adenoviruses and rhinovirus and some respiratory enveloped viruses including human respiratory syncytial viruses, influenza A, parainfluenza, SARS-CoV, and SARS-CoV-2 have shown the antiviral activity of cardiac glycosides, correlating their effect with Na+/K+-ATPase (NKA) modulation. Cardiac glycosides are secondary metabolites used to treat patients with cardiac insufficiency because they are the most potent inotropic agents. The effects of cardiac glycosides on NKA are dependent on cell type, exposure time, and drug concentration. They may also cause blockage of Na+ and K+ ionic transport or trigger signaling pathways. The antiviral activity of cardiac glycosides is related to cell signaling activation through NKA inhibition. Nuclear factor kappa B (NFκB) seems to be an essential transcription factor for SARS-CoV-2 infection. NFκB inhibition by cardiac glycosides interferes directly with SARS-CoV-2 yield and inflammatory cytokine production. Interestingly, the antiviral effect of cardiac glycosides is associated with tyrosine kinase (Src) activation, and NFκB appears to be regulated by Src. Src is one of the main signaling targets of the NKA α-subunit, modulating other signaling factors that may also impair viral infection. These data suggest that Src-NFκB signaling modulated by NKA plays a crucial role in the inhibition of SARS-CoV-2 infection. Herein, we discuss the antiviral effects of cardiac glycosides on different respiratory viruses, SARS-CoV-2 pathology, cell signaling pathways, and NKA as a possible molecular target for the treatment of COVID-19.

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In Vitro Antiviral Activity of a Series of Wild Berry Fruit Extracts against Representatives of Picorna-, Orthomyxo- and Paramyxoviridae

Natural Product Communications ◽

10.1177/1934578x1400900116 ◽

2014 ◽

Vol 9 (1) ◽

pp. 1934578X1400900 ◽

Cited By ~ 6

Author(s):

Lubomira Nikolaeva-Glomb ◽

Luchia Mukova ◽

Nadya Nikolova ◽

Ilian Badjakov ◽

Ivayla Dincheva ◽

...

Keyword(s):

Influenza Virus ◽

Antiviral Activity ◽

Influenza A ◽

Antiviral Effect ◽

Influenza Virus A ◽

Methanol Extracts ◽

Wide Range ◽

Berry Fruits ◽

Wild Berries

Wild berry species are known to exhibit a wide range of pharmacological activities. They have long been traditionally applied for their antiseptic, antimicrobial, cardioprotective and antioxidant properties. The aim of the present study is to reveal the potential for selective antiviral activity of total methanol extracts, as well as that of the anthocyanins and the non-anthocyanins from the following wild berries picked in Bulgaria: strawberry ( Fragaria vesca L.) and raspberry ( Rubus idaeus L.) of the Rosaceae plant family, and bilberry ( Vaccinium myrtillis L.) and lingonberry ( Vaccinium vitis-idaea L) of the Ericaceae. The antiviral effect has been tested against viruses that are important human pathogens and for which chemotherapy and/or chemoprophylaxis is indicated, namely poliovirus type 1 (PV-1) and coxsackievirus B1 (CV-B1) from the Picornaviridae virus family, human respiratory syncytial virus A2 (HRSV-A2) from the Paramyxoviridae and influenza virus A/H3N2 of Orthomyxoviridae. Wild berry fruits are freeze-dried and ground, then total methanol extracts are prepared. Further the extracts are fractioned by solid phase extraction and the non-anthocyanin and anthocyanin fractions are eluted. The in vitro antiviral effect is examined by the virus cytopathic effect (CPE) inhibition test. The results reveal that the total extracts of all tested berry fruits inhibit the replication of CV-B1 and influenza A virus. CV-B1 is inhibited to the highest degree by both bilberry and strawberry, as well as by lingonberry total extracts, and influenza A by bilberry and strawberry extracts. Anthocyanin fractions of all wild berries strongly inhibit the replication of influenza virus A/H3N2. Given the obtained results it is concluded that wild berry species are a valuable resource of antiviral substances and the present study should serve as a basis for further detailed research on the matter.

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The Sheep Tetherin Paralog oBST2B Blocks Envelope Glycoprotein Incorporation into Nascent Retroviral Virions

Journal of Virology ◽

10.1128/jvi.02751-14 ◽

2014 ◽

Vol 89 (1) ◽

pp. 535-544 ◽

Cited By ~ 4

Author(s):

Lita Murphy ◽

Mariana Varela ◽

Sophie Desloire ◽

Najate Ftaich ◽

Claudio Murgia ◽

...

Keyword(s):

Golgi Apparatus ◽

Antiviral Activity ◽

Vesicular Stomatitis Virus ◽

Envelope Glycoprotein ◽

Bone Marrow Stromal Cell ◽

Restriction Factor ◽

Enveloped Viruses ◽

Viral Particles ◽

Wide Range ◽

Vesicular Stomatitis

ABSTRACTBone marrow stromal cell antigen 2 (BST2) is a cellular restriction factor with a broad antiviral activity. In sheep, theBST2gene is duplicated into two paralogs termedoBST2AandoBST2B. oBST2A impedes viral exit of the Jaagsiekte sheep retroviruses (JSRV), most probably by retaining virions at the cell membrane, similar to the “tethering” mechanism exerted by human BST2. In this study, we provide evidence that unlike oBST2A, oBST2B is limited to the Golgi apparatus and disrupts JSRV envelope (Env) trafficking by sequestering it. In turn, oBST2B leads to a reduction in Env incorporation into viral particles, which ultimately results in the release of virions that are less infectious. Furthermore, the activity of oBST2B does not seem to be restricted to retroviruses, as it also acts on vesicular stomatitis virus glycoproteins. Therefore, we suggest that oBST2B exerts antiviral activity using a mechanism distinct from the classical tethering restriction observed for oBST2A.IMPORTANCEBST2 is a powerful cellular restriction factor against a wide range of enveloped viruses. Sheep possess two paralogs of theBST2gene calledoBST2AandoBST2B. JSRV, the causative agent of a transmissible lung cancer of sheep, is known to be restricted by oBST2A. In this study, we show that unlike oBST2A, oBST2B impairs the normal cellular trafficking of JSRV envelope glycoproteins by sequestering them within the Golgi apparatus. We also show that oBST2B decreases the incorporation of envelope glycoprotein into JSRV viral particles, which in turn reduces virion infectivity. In conclusion, oBST2B exerts a novel antiviral activity that is distinct from those of BST2 proteins of other species.

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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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Iminosugar antivirals: the therapeutic sweet spot

Biochemical Society Transactions ◽

10.1042/bst20160182 ◽

2017 ◽

Vol 45 (2) ◽

pp. 571-582 ◽

Cited By ~ 35

Author(s):

Dominic S. Alonzi ◽

Kathryn A. Scott ◽

Raymond A. Dwek ◽

Nicole Zitzmann

Keyword(s):

Endoplasmic Reticulum ◽

Protein Folding ◽

Antiviral Activity ◽

Broad Spectrum ◽

Antiviral Effect ◽

Sweet Spot ◽

Future Prospects ◽

Wide Range ◽

Viral Glycoproteins ◽

Endoplasmic Reticulum Protein

Many viruses require the host endoplasmic reticulum protein-folding machinery in order to correctly fold one or more of their glycoproteins. Iminosugars with glucose stereochemistry target the glucosidases which are key for entry into the glycoprotein folding cycle. Viral glycoproteins are thus prevented from interacting with the protein-folding machinery leading to misfolding and an antiviral effect against a wide range of different viral families. As iminosugars target host enzymes, they should be refractory to mutations in the virus. Iminosugars therefore have great potential for development as broad-spectrum antiviral therapeutics. We outline the mechanism giving rise to the antiviral activity of iminosugars, the current progress in the development of iminosugar antivirals and future prospects for this field.

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

Viruses ◽

10.3390/v13061085 ◽

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.

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Electron Cryotomography of Tula Hantavirus Suggests a Unique Assembly Paradigm for Enveloped Viruses

Journal of Virology ◽

10.1128/jvi.00057-10 ◽

2010 ◽

Vol 84 (10) ◽

pp. 4889-4897 ◽

Cited By ~ 95

Author(s):

Juha T. Huiskonen ◽

Jussi Hepojoki ◽

Pasi Laurinmäki ◽

Antti Vaheri ◽

Hilkka Lankinen ◽

...

Keyword(s):

Three Dimensional ◽

Hemorrhagic Fever ◽

Membrane Curvature ◽

Emerging Viruses ◽

Enveloped Viruses ◽

Viral Membrane ◽

Density Maps ◽

Virion Structure ◽

Electron Cryotomography ◽

Assembly Principles

ABSTRACT Hantaviruses (family Bunyaviridae) are rodent-borne emerging viruses that cause a serious, worldwide threat to human health. Hantavirus diseases include hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome. Virions are enveloped and contain a tripartite single-stranded negative-sense RNA genome. Two types of glycoproteins, GN and GC, are embedded in the viral membrane and form protrusions, or “spikes.” The membrane encloses a ribonucleoprotein core, which consists of the RNA segments, the nucleocapsid protein, and the RNA-dependent RNA polymerase. Detailed information on hantavirus virion structure and glycoprotein spike composition is scarce. Here, we have studied the structures of Tula hantavirus virions using electron cryomicroscopy and tomography. Three-dimensional density maps show how the hantavirus surface glycoproteins, membrane, and ribonucleoprotein are organized. The structure of the GN-GC spike complex was solved to 3.6-nm resolution by averaging tomographic subvolumes. Each spike complex is a square-shaped assembly with 4-fold symmetry. Spike complexes formed ordered patches on the viral membrane by means of specific lateral interactions. These interactions may be sufficient for creating membrane curvature during virus budding. In conclusion, the structure and assembly principles of Tula hantavirus exemplify a unique assembly paradigm for enveloped viruses.

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