Repurposing Chloroquine and Hydroxychloroquine for the Management of Coronavirus Disease-19

Abstract

Introduction: Coronavirus Disease-19 (COVID-19) pandemic has impacted adversely on global health and socio-economic activities. There is currently no licensed anti-SARS-CoV-2 drug. Objective: This review highlights some pharmacological properties of chloroquine and hydroxychloroquine, adverse effects, and prospects of repurposing them for the treatment of COVID-19. Materials and methods: Google scholar was employed in searching relevant published journal articles (n=122) in English. The search was later narrowed down to SARS-CoV-2, pathophysiology of COVID-19, available drugs for its management, clinical trials on repurposing drugs for COVID-19 therapy, and the role of chloroquine and hydroxychloroquine in its management. Results: Documented evidence revealed that chloroquine and hydroxychloroquine have antiviral and immune-modulatory properties. Their antiviral effect is due to inhibition of the spike proteins of SARS-CoV-2 from binding to the cellular transmembrane receptors, angiotensin converting enzyme-2 thereby preventing viral infections. Also, sequestration of these drugs into the lysosomes elevates lysosomal pH thus inhibiting lysosomal enzymatic functions vital for viral replication in those cells. Whereas, their immune-modulatory activity averts the inflammatory complications of COVID-19, particularly acute respiratory syndrome, by preventing cytokine storm through suppression of the production and excessive release of pro-inflammatory cytokines. The adverse effects, notably irreversible retinopathy and cardiac arrhythmias are rare but life-threatening when they occur. These are minimal with hydroxychloroquine compared to chloroquine. Conclusion: Chloroquine and hydroxychloroquine could be repurposed for COVID-19 cases because they are relatively effective, available, cheap, and extensively used for treating malaria and auto-immune diseases. Also, a viable vaccine is not yet developed whereas there is a pressing need to reduce the daily rise in morbidity and mortality associated with the disease. While we await results of the ongoing clinical trials, we recommend that their compassionate and/or experimental use should be with cautiousness by close monitoring for potential ocular and cardiovascular adverse effects and early withdrawal when observed.