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Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation
Kwong, Cheryl H.T.1; Mu, Jingfang2; Li, Shengke1; Fang, Yaohui2; Liu, Qianyun3; Zhang, Xiangjun1; Kam, Hiotong1; Lee, Simon M.Y.1; Chen, Yu3; Deng, Fei2; Zhou, Xi2,3; Wang, Ruibing1
2021-10
Source PublicationChinese Chemical Letters
ISSN1001-8417
Volume32Issue:10Pages:3019-3022
Abstract

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CQ was approved by the FDA for the emergency use authorization (EUA) in the fight against COVID-19 in the US, but later was revoked the EUA status due to the severe clinical toxicity.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 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.

KeywordChloroquine Covid-19 Cucurbit[7]Uril Host-guest Sars-cov-2
DOI10.1016/j.cclet.2021.04.008
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaChemistry
WOS SubjectChemistry, Multidisciplinary
WOS IDWOS:000722554600012
Scopus ID2-s2.0-85104434241
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Cited Times [WOS]:7   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionDEPARTMENT OF PHARMACEUTICAL SCIENCES
Institute of Chinese Medical Sciences
THE STATE KEY LABORATORY OF QUALITY RESEARCH IN CHINESE MEDICINE (UNIVERSITY OF MACAU)
Corresponding AuthorChen, Yu; Deng, Fei; Zhou, Xi; Wang, Ruibing
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, 999078, China
2.State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences (CAS), Wuhan, 430071, China
3.State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Kwong, Cheryl H.T.,Mu, Jingfang,Li, Shengke,et al. Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation[J]. Chinese Chemical Letters,2021,32(10):3019-3022.
APA 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.(2021).Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation.Chinese Chemical Letters,32(10),3019-3022.
MLA Kwong, Cheryl H.T.,et al."Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation".Chinese Chemical Letters 32.10(2021):3019-3022.
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