Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro
Liu et al.
, Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in..
, Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0 (In Vitro)
study showing that HCQ is effective in vitro
and less toxic than CQ. In addition to direct antiviral activity, HCQ is a safe and successful anti-inflammatory agent that has been used extensively in autoimmune diseases and can significantly decrease the production of cytokines and, in particular, pro-inflammatory factors. Therefore, in COVID-19 patients, HCQ may also contribute to attenuating the inflammatory response. Careful design of clinical trials is important to achieve efficient and safe control of the infection.14 In Vitro studies
support the efficacy of HCQ [Andreani, Clementi, Dang, Delandre, Faísca, Hoffmann, Liu, Ou, Purwati, Sheaff, Wang, Wang (B), Yao, Yuan]
Liu et al., 18 Mar 2020, peer-reviewed, 10 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: Liu et al. Cell Discovery (2020)6:16
Hydroxychloroquine, a less toxic derivative
of chloroquine, is effective in inhibiting
SARS-CoV-2 infection in vitro
Jia Liu1, Ruiyuan Cao2, Mingyue Xu1,3, Xi Wang1, Huanyu Zhang1,3, Hengrui Hu1,3, Yufeng Li1,3, Zhihong Hu
Wu Zhong2 and Manli Wang1
The outbreak of coronavirus disease 2019 (COVID-19)
caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/2019-nCoV) poses a serious
threat to global public health and local economies. As of
March 3, 2020, over 80,000 cases have been conﬁrmed in
China, including 2946 deaths as well as over 10,566
conﬁrmed cases in 72 other countries. Such huge numbers of infected and dead people call for an urgent
demand of effective, available, and affordable drugs to
control and diminish the epidemic.
We have recently reported that two drugs, remdesivir
(GS-5734) and chloroquine (CQ) phosphate, efﬁciently
inhibited SARS-CoV-2 infection in vitro1. Remdesivir is a
nucleoside analog prodrug developed by Gilead Sciences
(USA). A recent case report showed that treatment with
remdesivir improved the clinical condition of the ﬁrst
patient infected by SARS-CoV-2 in the United States2,
and a phase III clinical trial of remdesivir against SARSCoV-2 was launched in Wuhan on February 4, 2020.
However, as an experimental drug, remdesivir is not
expected to be largely available for treating a very large
number of patients in a timely manner. Therefore, of the
two potential drugs, CQ appears to be the drug of choice
for large-scale use due to its availability, proven safety
record, and a relatively low cost. In light of the preliminary clinical data, CQ has been added to the list of
Correspondence: Zhihong Hu (email@example.com) or Wu Zhong
(firstname.lastname@example.org) or Manli Wang (email@example.com)
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety
Mega-Science, Chinese Academy of Sciences, 430071 Wuhan, China
National Engineering Research Center for the Emergency Drug, Beijing
Institute of Pharmacology and Toxicology, 100850 Beijing, China
Full list of author information is available at the end of the article.
These authors contributed equally: Jia Liu, Ruiyuan Cao, Mingyue Xu
trial drugs in the Guidelines for the Diagnosis and
Treatment of COVID-19 (sixth edition) published by
National Health Commission of the People’s Republic
(N4-(7-Chloro-4-quinolinyl)-N1,N1-diethyl-1,4pentanediamine) has long been used to treat malaria and
amebiasis. However, Plasmodium falciparum developed
widespread resistance to it, and with the development of
new antimalarials, it has become a choice for the prophylaxis of malaria. In addition, an overdose of CQ can
cause acute poisoning and death3. In the past years, due to
infrequent utilization of CQ in clinical practice, its production and market supply was greatly reduced, at least in
China. Hydroxychloroquine (HCQ) sulfate, a derivative of
CQ, was ﬁrst synthesized in 1946 by introducing a
hydroxyl group into CQ and was demonstrated to be
much less (~40%) toxic than CQ in animals4. More
importantly, HCQ is still widely available to treat autoimmune diseases, such as systemic lupus erythematosus
and rheumatoid arthritis. Since CQ and HCQ share
similar chemical structures and mechanisms of acting as..
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