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Chloroquine

Chloroquine

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 trial 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 shown early evidence of being effective in treating COVID-19 in preliminary results in a small study on 30 patients in France. 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.



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. 



Timeline

March 18, 2020

Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro

February 4, 2020

Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro

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Further reading

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



Web

March 1, 2020

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



Web

March 4, 2020

Physicians work out treatment guidelines for coronavirus - Korea Biomedical Review



Web

February 13, 2020





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News

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Katherine Seley-Radtke
March 27, 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.
Safoora
March 23, 2020
The Siasat Daily
Hyderabad News, Bollywood, World, Islamic News
Eliott C. McLaughlin, CNN
March 23, 2020
CNN
As the world's health experts race to find treatments -- and eventually, a cure -- for the novel coronavirus, two drugs have jumped to the front of the conversation: chloroquine and hydroxychloroquine.
March 22, 2020
The Times of India
Europe News: A French researcher has reported successful trial of a new treatment line for Covid-19, with early tests suggesting it can stop the virus from becomin
Adam Rogers
March 19, 2020
Wired
The old malaria drug is getting used against the coronavirus. Tech enthusiasts are abuzz. One missing step: clinical trials.
Christopher Carbone
March 19, 2020
Fox News
Chloroquine, a drug that has been used to prevent and treat malaria, has shown promise in being a potential treatment for the novel cornavirus sweeping the globe, President Trump said Thursday.

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