Repurposed Drugs to Fight SARS-CoV-2, Chloroquine - Part 1

Repurposed Drugs to Fight SARS-CoV-2, Chloroquine - Part 1

Part 1, Chloroquine

Normally, we bring you blogs as well as snapshots of the Monocl database in our Through the Lens series. But these aren’t normal times and so for this series we will try our hand on a combination to provide you insights into what drug repurposing efforts are ongoing in the fight against SARS-CoV-2 and who the world-leading experts for these drugs are.

First up: Chloroquine

Early last week the first reports surfaced of a French doctor treating COVID19 patients with the old malaria drug chloroquine French-researcher-in-Marseille-posts-successful-Covid-19-coronavirus-drug-trial-results) with good success. Of the 24 patients treated with 600 mcg per day of Plaquenil only 25% were still contagious after six days, whereas in the untreated control group all patients were still contagious.

Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of COVID‐19: results of an open‐label non‐randomized clinical trial. International Journal of Antimicrobial Agents – In Press 17 March 2020 – DOI : 10.1016/j.ijantimicag.2020.105949

These results followed earlier studies with chloroquine in China where it is used to treat COVID19 patients in ongoing clinical trial. The researchers concluded

“Chloroquine phosphate, an old drug for treatment of malaria, is shown to have apparent efficacy and acceptable safety against COVID-19 associated pneumonia in multicenter clinical trials conducted in China.”

Within a day or two of the French study being published, everybody was talking about Chloroquine and the drug was backordered in all major online pharmacies.

A Brief History of Chloroquine

Legend has it, that Chloroquine has been used to treat malaria since the 1600s when it was brought to Europe from Peru. It was first extracted from the cinchona bark in 1820 and then became the reference treatment for intermittent fever. Since then Plasmodium falciparum, the unicellular protozoan parasite that causes malaria, has developed widespread resistance against chloroquine and the drug is mainly used in malaria prophylaxis.

[From Wikipedia, the free encyclopedia](https://en.wikipedia.org/wiki/Chloroquine)

Hydroxychloroquine sulfate (HCQ), a less toxic derivative of chloroquine, is mainly used to treat autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. It is widely available and cheap to manufacture and therefore presents a desirable drug in the fight against SARS-CoV-2.

CQ and HCQ - Mechanism of Action

How is a compound that kills protozoans effective against a virus? Both HCQ and CQ are weak bases that elevate the pH of acidic intracellular organelles such as endosomes and lysosomes which are essential for membrane fusion. CQ and HCQ are effectively inhibiting entry of the virus into the host cell as well as transport of the virion post-entry and with that impeding the release of the viral genome. HCQ may contribute in a different way to improving COVID19 patients’ condition: it is used as an anti-inflammatory because it can significantly decrease the production of cytokines. Clinical studies have shown that in critically ill COVID19 patients a cytokine storm is associated with disease severity. The anti-inflammatory HCQ can temper this inflammatory response.

Adverse events

While both CQ and HCQ have been in use for a long time, they are not without adverse events.

  • HCQ is relatively well tolerated with the most common adverse reactions being stomach pain, nausea, vomiting, and headache.
  • CQ’s list of adverse events is longer and includes similar issues as reported for HCQ but in addition can lead to blurred vision, unusual behavior or mood changes, seizures and a long list of other health challenges.

Who is Who in HCQ and CQ Research

A special Through the Lens for researchers that are focusing on HCQ and CQ

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