Biodiversity as a Source of Potent and Selective Inhibitors of Chikungunya Virus Replication

Leyssen, Pieter; Smadja, Jacqueline; Rasoanaivo, Philippe; Gurib-Fakim, Ameenah; Mahomoodally, Mohamad Fawzi; Canard, Bruno; Guillemot, Jean‐Claude; Litaudon, Marc; Guéritte, Françoise

doi:10.1002/9781118460566.ch11

Cited by 7 publications

(9 citation statements)

References 41 publications

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“…In contrast, the discovery of antiviral properties of macrocyclic diterpenes against CHIKV is much more recent [20,21,22,23,24] as it followed the chikungunya African outbreak in the 2000s and its subsequent emergence in the Indian Ocean [24]. The main vectors are Aedes mosquitoes from the Culicidae family such as A. furcifer , A. africanus , A. luteocephalus , A. taylori and A. aegypti .…”

Section: Introductionmentioning

confidence: 99%

“…As CHIKV reached epidemic level, the quest for novel and selective antiviral compounds was launched on a large scale. A project entitled ‘Biodiversity and emerging viruses in the Indian Ocean: selection of drug candidates targeting the Chikungunya virus′, was selected by the Centre for Research and Monitoring of Emerging Diseases in the Indian Ocean (CRVOI) for financial support and was developed between 2009 and 2011 [24]. The main objective was to discover and characterize new selective antiviral compounds from the plant biodiversity of the Indian Ocean (Madagascar, Reunion and Mauritius), which was then extended to that of New Caledonian and Mediterranean flora.…”

Section: Introductionmentioning

confidence: 99%

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Macrocyclic Diterpenoids from Euphorbiaceae as A Source of Potent and Selective Inhibitors of Chikungunya Virus Replication

Rémy

Litaudon

2019

Molecules

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Macrocyclic diterpenoids produced by plants of the Euphorbiaceae family are of considerable interest due to their high structural diversity; and their therapeutically relevant biological properties. Over the last decade many studies have reported the ability of macrocyclic diterpenoids to inhibit in cellulo the cytopathic effect induced by the chikungunya virus. This review; which covers the years 2011 to 2019; lists all macrocyclic diterpenoids that have been evaluated for their ability to inhibit viral replication. The structure–activity relationships and the probable involvement of protein kinase C in their mechanism of action are also detailed.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Macrocyclic Diterpenoids from Euphorbiaceae as A Source of Potent and Selective Inhibitors of Chikungunya Virus Replication

Rémy

Litaudon

2019

Molecules

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“…Interestingly, several of these scaffolds have recently been shown to protect BGM (buffalo green monkey) cells from chikungunya virus (CHIKV)-induced cell death, with the most recent report specifically implicating a PKC-dependent pathway . CHIKV is a mosquito-borne arbovirus that is becoming an increasingly prominent public health threat . Since its first appearances in the Americas in late 2013, over one million confirmed or suspected cases have been reported .…”

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confidence: 99%

Simplified Bryostatin Analogues Protect Cells from Chikungunya Virus-Induced Cell Death

et al. 2016

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Chikungunya virus (CHIKV) is a mosquito-borne alphavirus showing a recent resurgence and rapid spread worldwide. While vaccines are under development, there are currently no therapies to treat this disease, except for over-the-counter (OTC) analgesics, which alleviate the devastating arthritic and arthralgic symptoms. To identify novel inhibitors of the virus, analogues of the natural product bryostatin 1, a clinical lead for the treatment of cancer, Alzheimer’s disease, and HIV eradication, were investigated for in vitro antiviral activity and were found to be among the most potent inhibitors of CHIKV replication reported to date. Bryostatin-based therapeutic efforts and even recent anti-CHIKV strategies have centered on modulation of protein kinase C (PKC). Intriguingly, while the C ring of bryostatin primarily drives interactions with PKC, A- and B-ring functionality in these analogues has a significant effect on the observed cell-protective activity. Significantly, bryostatin 1 itself, a potent pan-PKC modulator, is inactive in these assays. These new findings indicate that the observed anti-CHIKV activity is not solely mediated by PKC modulation, suggesting possible as yet unidentified targets for CHIKV therapeutic intervention. The high potency and low toxicity of these bryologs make them promising new leads for the development of a CHIKV treatment.

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“…After the massive CHIKV outbreak in the Indian Ocean region in 2005–2006, a large-scale quest for novel and selective antiviral compounds was initiated. A project called “Biodiversity and emerging viruses in the Indian Ocean: selection of drug candidates targeting the Chikungunya virus” was financially supported by the Center for Research and Monitoring of Emerging Diseases in the Indian Ocean (CRVOI) and carried out from March 2009 to December 2011 ( 195 ). Its goal was to find new selective antiviral compounds derived from plants from the Indian Ocean Region, an area with a vast botanical biodiversity.…”

Section: Antivirals Against Chikungunya Virusmentioning

confidence: 99%

Current and Promising Antivirals Against Chikungunya Virus

Hucke¹,

Bugert²

2020

Front. Public Health

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Chikungunya virus (CHIKV) is the causative agent of chikungunya fever (CHIKF) and is categorized as a(n) (re)emerging arbovirus. CHIKV has repeatedly been responsible for outbreaks that caused serious economic and public health problems in the affected countries. To date, no vaccine or specific antiviral therapies are available. This review gives a summary on current antivirals that have been investigated as potential therapeutics against CHIKF. The mode of action as well as possible compound targets (viral and host targets) are being addressed. This review hopes to provide critical information on the in vitro efficacies of various compounds and might help researchers in their considerations for future experiments.

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Biodiversity as a Source of Potent and Selective Inhibitors of Chikungunya Virus Replication

Cited by 7 publications

References 41 publications

Macrocyclic Diterpenoids from Euphorbiaceae as A Source of Potent and Selective Inhibitors of Chikungunya Virus Replication

Macrocyclic Diterpenoids from Euphorbiaceae as A Source of Potent and Selective Inhibitors of Chikungunya Virus Replication

Simplified Bryostatin Analogues Protect Cells from Chikungunya Virus-Induced Cell Death

Current and Promising Antivirals Against Chikungunya Virus

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