Natural antiviral compound silvestrol modulates human monocyte‐derived macrophages and dendritic cells

Blum, Leonard; Geißlinger, Gerd; Parnham, Michael J.; Grünweller, Arnold; Schiffmann, Susanne

doi:10.1111/jcmm.15360

Cited by 23 publications

(30 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The development of plant-derived substances used as nutraceuticals and capable of inhibiting the infection of emerging viruses represents an attractive and eco-friendly strategy [ 41 ]. Indeed, several studies have shown that plants represent a promising source of antivirals against emerging viruses [ 17 , 18 , 19 , 22 , 23 , 24 , 30 , 42 , 43 ]. In this study, we showed for the first time that papaya fruit pulp inhibited the infection of A549 cells by the epidemic ZIKV without reducing cell viability.…”

Section: Resultsmentioning

confidence: 99%

“…Neither an effective treatment nor a vaccine is available for ZIKV. Given that several countries around the world are at risk of ZIKV outbreaks, it is still of high importance to develop antiviral strategies that include the use of nutraceuticals that can be used to prevent ZIKV infection [17][18][19][20][21]. Several polyphenol-rich extracts from Reunion Island have been reported to prevent ZIKV infection in vitro [22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

show abstract

“…This mRNA selectivity also might explain the low toxicity of rocaglates in primary cells and animals [ 98 ]. The cytotoxic effects of rocaglates observed in primary cells might be correlated with cellular proliferative activity [ 99 ].…”

Section: Mechanism Of Action Of Rocaglatesmentioning

confidence: 99%

“…Such a framework would provide a solid mechanistic foundation to help predict whether a novel viral strain might be sensitive to rocaglates following an initial sequence-based determination of its putative translation mechanism [ 125 , 126 ]. The framework would ideally also include comprehensive pharmacological profiles of candidate rocaglates, and in particular of their immunomodulatory effects, to maximize treatment safety during a potential emergency rollout in the initial phases of an outbreak [ 99 , 127 ]. A consensus on what the minimum validation criteria of such foundational research need to be would provide the basis for proceeding to preclinical in vivo studies.…”

Section: A Pan-antiviral Translational Roadmap For Rocaglatesmentioning

confidence: 99%

Targeting the DEAD-Box RNA Helicase eIF4A with Rocaglates—A Pan-Antiviral Strategy for Minimizing the Impact of Future RNA Virus Pandemics

Taroncher-Oldenburg¹,

Müller

Obermann

et al. 2021

Microorganisms

Self Cite

View full text Add to dashboard Cite

The increase in pandemics caused by RNA viruses of zoonotic origin highlights the urgent need for broad-spectrum antivirals against novel and re-emerging RNA viruses. Broad-spectrum antivirals could be deployed as first-line interventions during an outbreak while virus-specific drugs and vaccines are developed and rolled out. Viruses depend on the host’s protein synthesis machinery for replication. Several natural compounds that target the cellular DEAD-box RNA helicase eIF4A, a key component of the eukaryotic translation initiation complex eIF4F, have emerged as potential broad-spectrum antivirals. Rocaglates, a group of flavaglines of plant origin that clamp mRNAs with highly structured 5′ untranslated regions (5′UTRs) onto the surface of eIF4A through specific stacking interactions, exhibit the largest selectivity and potential therapeutic indices among all known eIF4A inhibitors. Their unique mechanism of action limits the inhibitory effect of rocaglates to the translation of eIF4A-dependent viral mRNAs and a minor fraction of host mRNAs exhibiting stable RNA secondary structures and/or polypurine sequence stretches in their 5′UTRs, resulting in minimal potential toxic side effects. Maintaining a favorable safety profile while inducing efficient inhibition of a broad spectrum of RNA viruses makes rocaglates into primary candidates for further development as pan-antiviral therapeutics.

show abstract

“…In these settings, the ability of rocaglates to guide monocyte/macrophages towards M1-like phenotype and inhibit triggers of the alternative, M2-like, activation may be particularly useful. Silvestrol has been shown to display a broad spectrum of antiviral activities including Corona-, Ebola-, Zika-, Picorna-, Hepatis E and Chikungunya viruses (20,59). Recent analysis of a SARS-CoV-2 protein interaction map predicted that the rocaglate target eIF4A could be the antiviral drug target (60).…”

Section: Macrophage Activation By Rocaglates Improves Bacterial Controlmentioning

confidence: 99%

Channeling macrophage polarization via selective translation inhibition by rocaglates increases macrophage resistance to Mycobacterium tuberculosis

Chatterjee

Yabaji

Bhattacharya

et al. 2019

Preprint

View full text Add to dashboard Cite

24The increasing problem of infectious diseases caused by antibiotic-resistant bacteria has 25 intensified a search for novel host-directed therapies aimed at either boosting immune-mediated 26 bacterial control or reducing immunopathology. Macrophages play central roles in eliminating 27 pathogens as well as in tissue homeostasis and repair via alternative activation programs, M1-28 like and M2-like, respectively. Macrophages of both phenotypes are often present at the sites of 29 chronic unresolved inflammation, such infectious granulomas and solid tumors, where the M2-30 like macrophages generate microenvironment conducive for pathogen survival or tumor 31 progression. 32Interferon-gamma is a major cytokine that drives M1-like macrophage activation, which 33 is essential for control of intracellular bacterial pathogens. To evaluate M1-like macrophage 34 polarization as a broad therapeutic strategy, we searched for small molecules capable of 35 enhancing effects of low concentrations of IFNγ on M1 macrophage polarization. We 36 identified synthetic rocaglates that potentiated macrophages responses to low concentrations 37 of IFNγ. Although known as potent translation inhibitors in tumor cell lines, in primary 38 macrophages select rocaglates induced the upregulation of IRF1, a master regulator of IFNγ 39-activated pathways, stimulated autophagy and increased macrophage resilience to oxidative 40 stress. In contrast, rocaglates inhibited macrophage responsiveness to IL-4, a prototypical 41 activator of the M2-like phenotype. The M1-like macrophage programing by rocaglates was 42 mechanistically linked to selective translation inhibition and modulation of MAP kinase 43 network. 44Thus, rocaglates represent a novel class of immunomodulators that can enforce 45 macrophage polarization towards the M1-like phenotype in complex microenvironments 46 3 associated with hypofunction of type 1 and/or hyperactivation of type 2 immunity, e.g., 47chronic bacterial infections, allergies and, possibly, certain tumors. 48 49 50 51The increasing problem of infectious diseases caused by antibiotic-resistant bacteria has 52 intensified a search for novel therapeutic approaches. Among them are host-directed therapies 53 aimed at either boosting immune-mediated bacterial control or reducing immunopathology, 54 broadly referred to as mechanisms of host resistance or disease tolerance, respectively (1). 55Many intracellular bacterial pathogens reside in macrophages, the very cells of innate immune 56 system whose major function is to eliminate invading pathogens. This paradox is enabled by 57 macrophages' plasticity, which successful pathogens exploit to create cellular niches for 58 persistence and replication within inflamed tissue of susceptible hosts. 59To combat intracellular bacteria, macrophages activate cell autonomous defense 60 mechanisms, such as phagocytosis, production of highly toxic reactive oxygen and nitrogen 61 species, bactericidal peptides, as well as phagosome maturation and autophagy to deliver the 62 ingested pat...

show abstract

Natural antiviral compound silvestrol modulates human monocyte‐derived macrophages and dendritic cells

Cited by 23 publications

References 50 publications

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

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

Targeting the DEAD-Box RNA Helicase eIF4A with Rocaglates—A Pan-Antiviral Strategy for Minimizing the Impact of Future RNA Virus Pandemics

Channeling macrophage polarization via selective translation inhibition by rocaglates increases macrophage resistance to Mycobacterium tuberculosis

Contact Info

Product

Resources

About