Published: Effects of chloroquine on viral infections: an old drug against today's diseases.
This is a review article. intended as a personal take on THE LANCET Infectious Diseases (Vol 3 November 2003). The first two paragraphs are a great summary of what happened to CQ since its discovery:
“Chloroquine is a 9-aminoquinoline that has been known since 1934. Specifically synthesised to be used as an antimalarial agent, chloroquine was subsequently shown to have immunomodulatory properties that have encouraged its application in the treatment of autoimmune diseases such as rheumatoid arthritis. For this specific pathology, chloroquine and its hydroxy-analogue hydroxychloroquine have represented a valid contribution to the available pharmacological tools, since they proved able to slow down the progress of the disease while showing limited toxicity.1
Unfortunately, chloroquine is being gradually dismissed from antimalarial therapy and prophylaxis, due to the continuous emergence of chloroquine-resistant Plasmodium falciparum strains. However, the tolerability, low cost, and immunomodulatory properties of chloroquine/hydroxychloroquine are associated with biochemical effects that suggest a potential use in viral infections, some of whose symptoms may result from the inflammatory response.2,3 We raise the question of whether this old drug whose parent compound, quinine, was isolated in the late 19th century from the bark of the tropical cinchona tree, may experience a revival in the clinical management of viral diseases of the era of globalisation.”
The article describes mechanisms by which one could expect a anti-viral effect. Then, it goes on to safety considerations, where they seem to understand this medicament as presenting "limited and well-preventable toxicity and may thus result in a low risk/benefit balance at least when it is used in life-threatening conditions.” Also: “A recent study (30) provided encouraging results on the safety of a high dosage of the drug (up to 500 mg of chloroquine base per day) even during pregnancy." This is the dose in the French scientists first article.
After talking about HIV /AIDS. They proceed to SARS: “Based on the effects of chloroquine/hydroxychloroquine on several enveloped viruses and on immune activation, we raise the hypothesis that this drug might be of some use for the clinical management of SARS. At present, any attempt to treat this disease with known antiviral drugs—namely ribavirin and oseltamivir—has been inconclusive.49 Corticosteroids may be of some benefit in controlling the inflammatory response at the lung level 50 but may also cause uncontrolled immunodepression resulting in pulmonary superinfection. The causative agent of SARS has recently been described as a new coronavirus.51,52 Recent studies support the idea that coronaviridae infect their target cells by an endocytic pathway and that chloroquine might inhibit their replication.53,54 ” . After discussing HCoV-229E (human coronavirus) in cells and their possible treatment, they add: “This result indicates that endosomal transport is needed for HCoV-229E infection. Cells treated with chloroquine expressed decreased amounts of HCoV-229E antigens.53 Preliminary data obtained from our group confirm these reports and show that chloroquine potently inhibits the replication of a canine coronavirus at therapeutically reachable concentrations (C Buonavoglia et al, University of Bari, Italy; unpublished). Although the SARS coronavirus is distinct with unique characteristics, it is tempting to ask whether chloroquine might affect SARS coronavirus replication as well.”
To answer their question: “At present it is difficult to answer the question of whether old chloroquine will be able to live a “second youth”. Due to its main effect—ie, raising endosomal pH—the drug has an exceptionally broad spectrum of antimicrobial activity that could be exploited in many infections. Results obtained in the prophylaxis of Q fever indicate that chloroquine/hydroxychloroquine can be successfully used in the clinical management of infections other than malaria.59 As regards viral diseases, what is clear is that the drug has antiviral and immunomodulatory effects that warrant particular consideration." And: “Finally, we want to share with the scientific community the speculative hypothesis that chloroquine/hydroxychloroquine, due to its antiviral and anti-inflammatory properties, may have some effect on SARS. We emphasise the need of testing in cell cultures infected with SARS coronavirus the effects of chloroquine, as well as those of other substances possessing in-vitro activity against members of the coronaviridae family. ” My italics.
Thus, he explains why this hypothesis makes sense, explaining why that could be so against SARS-CoV. He cites works from 2001 on HCQ against HIV/AIDS to sustain HCQ as antiviral.
On HCQ: Synthesized first in 1946 by Surrey and Hammer.
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