Abstract
Chloroquine and its derivatives have been used since ages to treat malaria and have also been approved by the FDA to treat autoimmune diseases. The drug employs pH-dependent inhibition of functioning and signalling of the endosome, lysosome and trans-Golgi network, immunomodulatory actions, inhibition of autophagy and interference with receptor binding to treat cancer and many viral diseases. The ongoing pandemic of COVID-19 has brought the whole world on the knees, seeking an urgent hunt for an anti-SARS-CoV-2 drug. Chloroquine has shown to inhibit receptor binding of the viral particles, interferes with their replication and inhibits “cytokine storm”. Though multiple modes of actions have been employed by chloroquine against multiple diseases, viral diseases can provide an added advantage to establish the anti–SARS-CoV-2 mechanism, the in vitro and in vivo trials against SARS-CoV-2 have yielded mixed results. The toxicological effects and dosage optimization of chloroquine have been studied for many diseases, though it needs a proper evaluation again as chloroquine is also associated with several toxicities. Moreover, the drug is inexpensive and is readily available in many countries. Though much of the hope has been created by chloroquine and its derivatives against multiple diseases, repurposing it against SARS-CoV-2 requires large scale, collaborative, randomized and unbiased clinical trials to avoid false promises. This review summarizes the use and the mechanism of chloroquine against multiple diseases, its side-effects, mechanisms and the different clinical trials ongoing against “COVID-19”.
Highlights
Chloroquine, commonly known for the anti-malarial applications has evolved gradually as a magic medicine, effective against many diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple types of cancer and viruses
This review summarises chloroquine’s journey, from being an anti-malarial drug to a magic bullet against multiple diseases, its good and evil, results of clinical trials obtained so far and the future aspects, it holds along with its drawbacks as prophylaxis or drug to fight COVID-19
The studies by Patel and coworkers, claimed to have performed a multinational registry analysis using a cloud-based health-care data analytics platform, Surgisphere Corporation, Chicago, IL, United States, on the usage of hydroxychloroquine or chloroquine with or without a macrolide for the treatment of COVID-19. They reported an increased risk of in-hospital mortality and de-novo ventricular arrhythmia in response to the treatment which led to the inference that hydroxychloroquine or chloroquine, when used alone or with a macrolide does not offer any benefit to the COVID-19 patients, which contributed to the halt in worldwide clinical trials by the WHO on May 25, 2020
Summary
Chloroquine, commonly known for the anti-malarial applications has evolved gradually as a magic medicine, effective against many diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple types of cancer and viruses. There are evidence of both, pH-dependent and pHindependent role of chloroquine and its derivatives to inhibit the generation of autoantibodies and reducing the secretion of inflammatory cytokines (Macfarlane and Manzel, 1998; Thome et al, 2013). Though the development of resistance against diseasemodifying anti-rheumatic drugs (DMARDs) including chloroquine, has not been studied much, the role of ATP binding cassette (ABC) proteins responsible for drug efflux cannot be neglected (Jansen et al, 2003). 5–40 μM obstructs fusion of the flaviviral envelope protein Shiryaev et al
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