Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model
et al., Cell Research, 23, 300–302, doi:10.1038/cr.2012.165, Dec 2012
HCQ for COVID-19
1st treatment shown to reduce risk in
March 2020, now with p < 0.00000000001 from 424 studies, used in 59 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,200+ studies for
200+ treatments. c19early.org
|
CQ, a known autophagy inhibitor that is in clinical use, can efficiently ameliorate acute lung injury and dramatically improve the survival rate in mice infected with live avian influenza A H5N1 virus.
39 preclinical studies support the efficacy of HCQ for COVID-19:
1.
Shang et al., Identification of Cathepsin L as the molecular target of hydroxychloroquine with chemical proteomics, Molecular & Cellular Proteomics, doi:10.1016/j.mcpro.2025.101314.
2.
González-Paz et al., Biophysical Analysis of Potential Inhibitors of SARS-CoV-2 Cell Recognition and Their Effect on Viral Dynamics in Different Cell Types: A Computational Prediction from In Vitro Experimental Data, ACS Omega, doi:10.1021/acsomega.3c06968.
3.
Alkafaas et al., A study on the effect of natural products against the transmission of B.1.1.529 Omicron, Virology Journal, doi:10.1186/s12985-023-02160-6.
4.
Guimarães Silva et al., Are Non-Structural Proteins From SARS-CoV-2 the Target of Hydroxychloroquine? An in Silico Study, ACTA MEDICA IRANICA, doi:10.18502/acta.v61i2.12533.
5.
Nguyen et al., The Potential of Ameliorating COVID-19 and Sequelae From Andrographis paniculata via Bioinformatics, Bioinformatics and Biology Insights, doi:10.1177/11779322221149622.
7.
Yadav et al., Repurposing the Combination Drug of Favipiravir, Hydroxychloroquine and Oseltamivir as a Potential Inhibitor Against SARS-CoV-2: A Computational Study, Research Square, doi:10.21203/rs.3.rs-628277/v1.
8.
Hussein et al., Molecular Docking Identification for the efficacy of Some Zinc Complexes with Chloroquine and Hydroxychloroquine against Main Protease of COVID-19, Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129979.
9.
Baildya et al., Inhibitory capacity of Chloroquine against SARS-COV-2 by effective binding with Angiotensin converting enzyme-2 receptor: An insight from molecular docking and MD-simulation studies, Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129891.
10.
Noureddine et al., Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: molecular docking and DFT calculations, Journal of King Saud University - Science, doi:10.1016/j.jksus.2020.101334.
11.
Tarek et al., Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention, European Journal of Drug Metabolism and Pharmacokinetics, doi:10.1007/s13318-020-00640-6.
12.
Rowland Yeo et al., Impact of Disease on Plasma and Lung Exposure of Chloroquine, Hydroxychloroquine and Azithromycin: Application of PBPK Modeling, Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.1955.
13.
Hitti et al., Hydroxychloroquine attenuates double-stranded RNA-stimulated hyper-phosphorylation of tristetraprolin/ZFP36 and AU-rich mRNA stabilization, Immunology, doi:10.1111/imm.13835.
14.
Yan et al., Super-resolution imaging reveals the mechanism of endosomal acidification inhibitors against SARS-CoV-2 infection, ChemBioChem, doi:10.1002/cbic.202400404.
15.
Mohd Abd Razak et al., In Vitro Anti-SARS-CoV-2 Activities of Curcumin and Selected Phenolic Compounds, Natural Product Communications, doi:10.1177/1934578X231188861.
16.
Alsmadi et al., The In Vitro, In Vivo, and PBPK Evaluation of a Novel Lung-Targeted Cardiac-Safe Hydroxychloroquine Inhalation Aerogel, AAPS PharmSciTech, doi:10.1208/s12249-023-02627-3.
17.
Wen et al., Cholinergic α7 nAChR signaling suppresses SARS-CoV-2 infection and inflammation in lung epithelial cells, Journal of Molecular Cell Biology, doi:10.1093/jmcb/mjad048.
18.
Kamga Kapchoup et al., In vitro effect of hydroxychloroquine on pluripotent stem cells and their cardiomyocytes derivatives, Frontiers in Pharmacology, doi:10.3389/fphar.2023.1128382.
19.
Milan Bonotto et al., Cathepsin inhibitors nitroxoline and its derivatives inhibit SARS-CoV-2 infection, Antiviral Research, doi:10.1016/j.antiviral.2023.105655.
20.
Miao et al., SIM imaging resolves endocytosis of SARS-CoV-2 spike RBD in living cells, Cell Chemical Biology, doi:10.1016/j.chembiol.2023.02.001.
21.
Yuan et al., Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture, Communications Biology, doi:10.1038/s42003-022-03841-8.
22.
Faísca et al., Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2, Pharmaceutics, doi:10.3390/pharmaceutics14040877.
23.
Delandre et al., Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants, Pharmaceuticals, doi:10.3390/ph15040445.
24.
Purwati et al., An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia, PLOS One, doi:10.1371/journal.pone.0252302.
25.
Zhang et al., SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination, Cell Death & Differentiation, doi:10.1038/s41418-021-00782-3.
26.
Dang et al., Structural basis of anti-SARS-CoV-2 activity of hydroxychloroquine: specific binding to NTD/CTD and disruption of LLPS of N protein, bioRxiv, doi:10.1101/2021.03.16.435741.
27.
Shang (B) et al., Inhibitors of endosomal acidification suppress SARS-CoV-2 replication and relieve viral pneumonia in hACE2 transgenic mice, Virology Journal, doi:10.1186/s12985-021-01515-1.
28.
Wang et al., Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus, Phytomedicine, doi:10.1016/j.phymed.2020.153333.
29.
Sheaff, R., A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Chloroquine Activity, bioRxiv, doi:10.1101/2020.08.02.232892.
30.
Ou et al., Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2, PLOS Pathogens, doi:10.1371/journal.ppat.1009212.
31.
Andreani et al., In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect, Microbial Pathogenesis, doi:10.1016/j.micpath.2020.104228.
32.
Clementi et al., Combined Prophylactic and Therapeutic Use Maximizes Hydroxychloroquine Anti-SARS-CoV-2 Effects in vitro, Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704.
33.
Liu et al., Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0.
34.
Yao et al., In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237.
Yan et al., 4 Dec 2012, peer-reviewed, 8 authors.
Abstract: npg CQ ameliorates acute lung injury induced by H5N1 virus
300
LETTER TO THE EDITOR
Cell Research (2013) 23:300-302.
© 2013 IBCB, SIBS, CAS All rights reserved 1001-0602/13 $ 32.00
www.nature.com/cr
Anti-malaria drug chloroquine is highly effective in treating
avian influenza A H5N1 virus infection in an animal model
Cell Research (2013) 23:300-302. doi:10.1038/cr.2012.165; published online 4 December 2012
Dear Editor,
The recent controversial studies of man-made avian
flu viruses caused a media storm, and brought new concerns to the potential of an avian influenza H5N1 virus
pandemic, which has been pending since 1997 [1, 2].
Although the estimated mortality rate of avian influenza
A H5N1 virus infection in humans could be as high as
60%, the World Health Organization (WHO) phase of
pandemic alert is currently set at 3, due to that there has
not been human-to-human or community-level transmission (http://www.who.int/influenza/preparedness/pandemic/h5n1phase/en/index.html). However, the newly
created H5N1 virus strains, which are genetically altered,
are transmissible among ferrets, and thus may trigger a
real pandemic that could potentially result in millions
of deaths according to Science Insider [3]. While it is
arguably a bit too late to debate whether regulations
or mandatory reviews should be applied to these dualuse studies, in the matter of fact, these viruses that are
probably among the most dangerous infectious agents
known already exist. Therefore, a top priority at present
is to find effective prophylactic or therapeutic agents that
would help to control a pandemic of avian influenza A
H5N1 viruses.
Previous reports have demonstrated that the high mortality in humans infected with avian influenza A H5N1
is partly due to acute lung injury or the resulting severe
condition, acute respiratory distress syndrome (ARDS)
[4, 5]. There are few treatment choices for ARDS, aside
from mechanical supporting equipment and empirical
treatments. The use of cortisones is controversial.
We have recently discovered that avian influenza A
H5N1 virus infection causes acute lung injury by inducing autophagic alveolar epithelial cell death [6]. Importantly, we found that autophagy inhibitors are effective
in ameliorating murine acute lung injury induced by live
avian influenza A H5N1 virus infections [6]. We thus
hypothesize that if a drug that is currently in clinical use
can act to inhibit autophagy, then such a drug might be a
good candidate for treating H5N1 infections.
To test this, we have focused our efforts on chloroquine (CQ), as CQ is the only oral clinical drug that is
known to be an autophagy inhibitor [7]. CQ, or N′-(7chloroquinolin-4-yl)-N,N-diethyl-pentane-1,4-diamine,
was discovered in 1934 by Hans Andersag and his coworkers at Bayer Laboratories and was introduced into
clinical practice in 1947 as a prophylactic treatment for
malaria [8]. Currently, CQ and its hydroxyl form, HCQ,
are used as anti-inflammatory agents for the treatment of
rheumatoid arthritis, lupus erythematosus and amoebic
hepatitis. More recently, CQ has been studied for its potential use as an enhancing agent in cancer therapies as
well as novel antagonists to chemokine receptor CXCR4
in pancreatic cancer [8, 9].
We first tested whether CQ could inhibit cell death
in the human lung carcinoma A549 cells infected with
live avian influenza A H5N1 virus. The cell viability was
improved both prophylactically and therapeutically in
a dose-dependent manner with..
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