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Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation
- Source :
- Chinese Chemical Letters
- Publication Year :
- 2021
- Publisher :
- Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences., 2021.
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Abstract
- Graphical abstract Chloroquine (CQ), an antimalarial drug, was found to exhibit promising antiviral activity in vitro and in vivo at a high dosage, thus CQ was approved by the FDA for the emergency use authorization (EUA) in the fight against COVID-19 in the US, but later was revoked the EUA status due to the severe clinical toxicity. Herein, we show that supramolecular formulation of CQ by a macrocyclic host, curcurbit[7]uril (CB[7]), reduced its non-specific toxicity and improved its antiviral activity against coronavirus, working in synergy with CB[7].<br />The wide-spreading SARS-CoV-2 virus has put the world into boiling water for more than a year, however pharmacological therapies to act effectively against coronavirus disease 2019 (COVID-19) remain elusive. Chloroquine (CQ), an antimalarial drug, was found to exhibit promising antiviral activity in vitro and in vivo at a high dosage, thus CQ was approved by the FDA for the emergency use authorization (EUA) in the fight against COVID-19 in the US, but later was revoked the EUA status due to the severe clinical toxicity. Herein, we show that supramolecular formulation of CQ by a macrocyclic host, curcurbit[7]uril (CB[7]), reduced its non-specific toxicity and improved its antiviral activity against coronavirus, working in synergy with CB[7]. CB[7] was found to form 1:1 host-guest complexes with CQ, with a binding constant of ∼104 L/mol. The CQ-CB[7] formulation decreased the cytotoxicity of CQ against Vero E6 and L-02 cell lines. In particular, the cytotoxicity of CQ (60 µmol/L) against both Vero E6 cell line and L-02 cell lines was completely inhibited in the presence of 300 µmol/L and 600 µmol/L CB[7], respectively. Furthermore, the CB[7] alone showed astonishing antiviral activity in SARS-CoV-2 infected Vero E6 cells and Mouse hepatitis virus strain A59 (MHV-A59) infected N2A cells, and synergistically improved the antiviral activity of CQ-CB[7], suggesting that CB[7]-based CQ formulation has a great potential as a safe and effective antiviral agent against SARS-CoV-2 and other coronavirus.
- Subjects :
- viruses
02 engineering and technology
010402 general chemistry
medicine.disease_cause
01 natural sciences
Virus
Mouse hepatitis virus
In vivo
Chloroquine
medicine
Cytotoxicity
Curcurbit[7]uril
Coronavirus
biology
Chemistry
SARS-CoV-2
Communication
COVID-19
Host-guest
General Chemistry
021001 nanoscience & nanotechnology
biology.organism_classification
Virology
In vitro
0104 chemical sciences
Vero cell
0210 nano-technology
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 18785964 and 10018417
- Database :
- OpenAIRE
- Journal :
- Chinese Chemical Letters
- Accession number :
- edsair.doi.dedup.....79f533ef389dc30a5c0b88a87d03c0fd