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Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation

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...

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Autores principales: Kwong, Cheryl H.T., Mu, Jingfang, Li, Shengke, Fang, Yaohui, Liu, Qianyun, Zhang, Xiangjun, Kam, Hiotong, Lee, Simon M.Y., Chen, Yu, Deng, Fei, Zhou, Xi, Wang, Ruibing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019245/
https://www.ncbi.nlm.nih.gov/pubmed/33840982
http://dx.doi.org/10.1016/j.cclet.2021.04.008
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author Kwong, Cheryl H.T.
Mu, Jingfang
Li, Shengke
Fang, Yaohui
Liu, Qianyun
Zhang, Xiangjun
Kam, Hiotong
Lee, Simon M.Y.
Chen, Yu
Deng, Fei
Zhou, Xi
Wang, Ruibing
author_facet Kwong, Cheryl H.T.
Mu, Jingfang
Li, Shengke
Fang, Yaohui
Liu, Qianyun
Zhang, Xiangjun
Kam, Hiotong
Lee, Simon M.Y.
Chen, Yu
Deng, Fei
Zhou, Xi
Wang, Ruibing
author_sort Kwong, Cheryl H.T.
collection PubMed
description 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CQ was approved by the FDA for the emergency use authorization (EUA) in the fight against COVID-19 in the US, but later was revoked the EUA status due to the severe clinical toxicity.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 ∼10(4) 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.
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spelling pubmed-80192452021-04-06 Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation Kwong, Cheryl H.T. Mu, Jingfang Li, Shengke Fang, Yaohui Liu, Qianyun Zhang, Xiangjun Kam, Hiotong Lee, Simon M.Y. Chen, Yu Deng, Fei Zhou, Xi Wang, Ruibing Chin Chem Lett Communication 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 ∼10(4) 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. Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. 2021-10 2021-04-03 /pmc/articles/PMC8019245/ /pubmed/33840982 http://dx.doi.org/10.1016/j.cclet.2021.04.008 Text en © 2019 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Communication
Kwong, Cheryl H.T.
Mu, Jingfang
Li, Shengke
Fang, Yaohui
Liu, Qianyun
Zhang, Xiangjun
Kam, Hiotong
Lee, Simon M.Y.
Chen, Yu
Deng, Fei
Zhou, Xi
Wang, Ruibing
Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation
title Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation
title_full Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation
title_fullStr Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation
title_full_unstemmed Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation
title_short Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation
title_sort reviving chloroquine for anti-sars-cov-2 treatment with cucurbit[7]uril-based supramolecular formulation
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019245/
https://www.ncbi.nlm.nih.gov/pubmed/33840982
http://dx.doi.org/10.1016/j.cclet.2021.04.008
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