The antiparasitic drug niclosamide inhibits dengue virus infection by interfering with endosomal acidification independent of mTOR

@article{Kao2018TheAD,
  title={The antiparasitic drug niclosamide inhibits dengue virus infection by interfering with endosomal acidification independent of mTOR},
  author={Jo-Chi Kao and Wei-Chun HuangFu and Tsung‐Ting Tsai and Min-Ru Ho and Ming-Kai Jhan and Ting-Jing Shen and Po‐Chun Tseng and Yung-Ting Wang and Chiou-Feng Lin},
  journal={PLoS Neglected Tropical Diseases},
  year={2018},
  volume={12}
}
Background The antiparasitic agent niclosamide has been demonstrated to inhibit the arthropod-borne Zika virus. Here, we investigated the antiviral capacity of niclosamide against dengue virus (DENV) serotype 2 infection in vitro and in vivo. Principle finding Niclosamide effectively retarded DENV-induced infection in vitro in human adenocarcinoma cells (A549), mouse neuroblastoma cells (Neuro-2a), and baby hamster kidney fibroblasts (BHK-21). Treatment with niclosamide did not retard the… 

Figures from this paper

JMX0207, a niclosamide derivative with improved pharmacokinetics, suppresses Zika virus infection both in vitro and in vivo.

TLDR
A niclosamide derivative JMX0207 was identified which shows improved pharmacokinetics and efficacy against Zika virus both in vitro and in vivo and significantly reduced viremia in a ZIKV animal model.

Neutralization of Acidic Intracellular Vesicles by Niclosamide Inhibits Multiple Steps of the Dengue Virus Life Cycle In Vitro

TLDR
It is revealed that neutralization of low-pH intracellular compartments by niclosamide affects multiple steps of the DENV infectious cycle, and a previously uncharacterized mechanism of action of the drug is highlighted.

Niclosamide for Covid-19: bridging the gap

TLDR
NCL has anti-inflammatory and immune regulatory effects by modulating the release of pro-inflammatory cytokines, inhibition of NF-κB /NLRP3 inflammasome and mTOR signaling pathway, and has an anti-SARS-CoV-2 effect via interruption of viral life-cycle and/or induction of cytopathic effect.

Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine

TLDR
Novel activities of obatoclax and emetine are identified against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures and reinforce the arsenal of available antiviral therapeutics pending the results of further in vitro and in vivo tests.

Niclosamide reverses SARS-CoV-2 control of lipophagy

TLDR
Data support the consideration of niclosamide as a potential COVID-19 therapeutic given its modulation of lipophagy leading to the reduction of virus egress and the subsequent regulation of key lipid mediators of pathological inflammation.

Developing Cytokine Storm-Sensitive Therapeutic Strategy in COVID-19 Using 8P9R Chimeric Peptide and Soluble ACE2

TLDR
A two-step treatment strategy can be considered as a personalized clinical therapy for COVID-19, that can prevent morbidity and mortality in the future.

Obatoclax inhibits SARS-CoV-2 entry by altered endosomal acidification and impaired cathepsin and furin activity in vitro

TLDR
Obatoclax is identified as a novel effective antiviral compound that keeps SARS-CoV-2 at bay by blocking both endocytosis and membrane fusion and should be further explored as a clinical drug for the treatment of COVID-19.

References

SHOWING 1-10 OF 36 REFERENCES

Niclosamide Is a Proton Carrier and Targets Acidic Endosomes with Broad Antiviral Effects

TLDR
It is demonstrated that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.

Suppressing Dengue-2 Infection by Chemical Inhibition of Aedes aegypti Host Factors

TLDR
Proof-of-principle is provided that chemical inhibition or RNAi-mediated depletion of the DENV HFs vATPase and IMPDH can be used to suppress DENV infection of adult A. aegypti mosquitoes, which may translate to a reduction in DENV transmission.

Novel Dengue Virus NS2B/NS3 Protease Inhibitors

TLDR
The selective and noncompetitive inhibition of the serotype 2 and 3 dengue virus PR in vitro and in cells by benzothiazole derivatives exhibiting 50% inhibitory concentrations (IC50s) in the low-micromolar range is reported.

Blockade of dengue virus infection and viral cytotoxicity in neuronal cells in vitro and in vivo by targeting endocytic pathways

TLDR
Results demonstrate that clathrin mediated endocytosis of DENV followed by endosomal acidification-dependent viral replication in neuronal cells, which can lead to neurotoxicity, is demonstrated.

Recent trends in ZikV research: A step away from cure.

Niclosamide: Beyond an antihelminthic drug

Dengue Virus NS2B/NS3 Protease Inhibitors Exploiting the Prime Side

TLDR
These cyclic peptides reported here as DENV protease inhibitors provide novel scaffolds that enable exploiting the prime side of the protease active site, with the aim of achieving better specificity and lower hydrophilicity than those of current scaffolds in the design of antiflaviviral inhibitors.