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Chemical compound and drug used to treat malaria, autoimmune disease and other conditions

Chloroquine is quinoline derivative and a drug in widespread use since 1945 for treatment of malaria, autoimmune and other conditions. Chloroquine as an antimalarial agent given by tablet, syrup or injection as chloroquine phosphate or chloroquine sulfate. Chloroquine has been shown to inhibit parasitic enzyme heme polymerase that converts toxic heme into non-toxic hemazoin, resulting in accumulation of toxic heme inside the parasite. Chloroquine is also thought to interfere with biosynthesis of nucleic acids. The agent shows chemosensitizing and radiosensitizing activities in cancer which may be due to inhibition of autophagy. For malaria chloroquine is used for prevention and as therapy. Chloroquine treats extraintestinal amebiasis and acts as an anti-inflammatory agent in treating rheumatoid arthritis and lupus erythematosus. Chloroquine is not found in individuals unless they have taken the drug. The mechanism of action of chloroquine is not well understood. The drug does not have significant detrimental side effects and can be taken by children and pregnant and nursing mothers.

Chloroquine has been reported to be an effective antiviral therapeutic against COVID-19 in treatments done in China and South Korea, with clinical trials ongoing as of March 2020. Treatment with chloroquine tablets was reported to show favorable outcomes such as faster time to recover and shorter hospital stay in people with COVID-19 infections. Laboratory research from the US CDC shows chloroquine also has potential to treat prophylactically. Chloroquine is being investigated to treat COVID-19 in the form of chloroquine phosphate or hydroxychloroquine sulfate which are sometimes referred to as chloroquine and hydroxychloroquine respectively.

As of March 26, 2020 the NIH Clinical Trials database showed 18 clinical trials listing hydroxychloroquine as an intervention. Hydroxychloroquine alone and in combination with the the antibiotic azithromycin (aka Zithromas or Azithrocin) have reported early evidence of being effective in treating COVID-19 in preliminary results in a small study on 30 patients in France, led by Didier Raoult. Controls in the study were patients who refused treatment, had exclusion criteria and patients in other medical centers that did not receive hydroxychloroquine. According to the paper Azithromycin was given to some patients to prevent bacterial super-infection. Azithromycin is also known to have immunomodulatory effects.It is not clear if differences between patients that received hydroxychoroquine alone and the combination therapy may be due to differences in the patient's viral load between the two groups. Subsequent results from Raoult's group have been released where all patients were given the hydroxychloroquine and azithromycin combination.

A randomized controlled trial comparing patients treated with hydroxychloroquine and a control group with 30 patients performed by researchers at Fudan University, Shanghai found no difference between the hydroxychloroquine and control groups in the time it took to achieve negative throat swabs for the virus and normalization of body temperature and radiological progression by CT imaging. The authors noted that a larger sample size was needed to assess the effects of hydroxychloroquine on COVID-19.

A randomized controlled trial conducted by researchers at Wuhan University including 62 patients found that time to clinical recovery, based on clinical characteristics and radiological results 5 days after treatment, was significantly shortened in the hydroxychloroquine group.

Mechanism for antiviral activity

The antiviral activity of chloroquine is thought to depend on the extent that the virus utilizes endosomes for entry. SARS-CoV-2 and other coronaviruses are enveloped viruses that use endocytosis prior to fusion with the host membrane. Post infection, chloroquine raises the pH and inhibits on-going fusion events between the virus and endosomes. Chloroquine is also thought to inhibit the replicative path of the virus. The drug enters cells and crosses endosomal membranes. Inside the endosome, nitorogens in chloroquine (and quinines) absorb hydrogen and prevent acidification, holding the endosome at a higher pH than is functional for the enzymes needed for hydrolysis reactions needed for coronavirus replication.

As a preventative treatment prior to infection, chloroquine is thought to impair terminal glycosylation of the ACE2 receptor it uses to enter cells. This may result in reduced binding between ACE2 and the spike protein on SARS-CoV-2, inhibiting initiation of infection.


Further Resources


Notice on Adjusting the Usage and Dosage of Chloroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia


March 1, 2020

Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional 7th Edition)


March 4, 2020

Physicians work out treatment guidelines for coronavirus - Korea Biomedical Review


February 13, 2020


November 9, 2020
Hydroxychloroquine, Azithromycin and Zinc for the Treatment of COVID-19 in the Outpatient Setting - Full Text View.
Mark Terry
May 22, 2020
The study found that of the 15,000 patients who received either of the drugs were almost twice as likely to die compared to the patients who did not receive them. The research was published in the journal The Lancet.
April 30, 2020
International Business Times UK
Hydroxychloroquine and Chloroquine are just one of the many drugs that have been promoted by doctors around the world.
Heidi Ledford
April 28, 2020
Scientific American
Scientific American is the essential guide to the most awe-inspiring advances in science and technology, explaining how they change our understanding of the world and shape our lives.
April 24, 2020
Effectiveness and Safety of Medical Treatment for SARS-CoV-2 (COVID-19) in Colombia - Full Text View.


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