Citation: Cheryl H.T. Kwong, Jingfang Mu, Shengke Li, Yaohui Fang, Qianyun Liu, Xiangjun Zhang, Hiotong Kam, Simon M.Y. Lee, Yu Chen, Fei Deng, Xi Zhou, Ruibing Wang. Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation[J]. Chinese Chemical Letters, ;2021, 32(10): 3019-3022. doi: 10.1016/j.cclet.2021.04.008 shu

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

Cheryl H.T. Kwong ^{a, 1} ,
Jingfang Mu ^{b, 1} ,
Shengke Li ^a ,
Yaohui Fang ^b ,
Qianyun Liu ^c ,
Xiangjun Zhang ^a ,
Hiotong Kam ^a ,
Simon M.Y. Lee ^a ,
Yu Chen ^{c, *,} ,
Fei Deng ^{b, *,} ,
Xi Zhou ^{b, c, **,} ,
Ruibing Wang ^{a, *,}

a.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China
b.
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences (CAS), Wuhan 430071, China
c.
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China

^**

Received Date: 23 February 2021
Revised Date: 31 March 2021
Accepted Date: 1 April 2021
Available Online: 3 April 2021

Figures(5)

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CQ was approved by the FDA for the emergency use authorization (EUA) in the fight against COVID-19 in the US, but later was revoked the EUA status due to the severe clinical toxicity.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.
- Host-guest,
- Chloroquine,
- Cucurbit[7]uril,
- SARS-CoV-2,
- COVID-19
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