Abstract
Hydroxychloroquine has gained much attention as one of the candidate drugs that can be repurposed as a prophylactic agent against SARS-CoV-2, the agent responsible for the COVID-19 pandemic. Due to high transmissibility and presence of asymptomatic carriers and presymptomatic transmission, there is need for a chemoprophylactic agent to protect the high-risk population. In this review, we dissect the currently available evidence on hydroxychloroquine prophylaxis from a clinical and pharmacological point of view. In vitro studies on Vero cells show that hydroxychloroquine effectively inhibits SARS-CoV-2 by affecting viral entry and viral transport via endolysosomes. However, this efficacy has failed to replicate in in vivo animal models as well as in most clinical observational studies and clinical trials assessing pre-exposure prophylaxis and postexposure prophylaxis in healthcare workers. An analysis of the pharmacology of HCQ in COVID-19 reveals certain possible reasons for this failure—a pharmacokinetic failure due to failure to achieve adequate drug concentration at the target site and attenuation of its inhibitory effect due to the presence of TMPRSS2 in airway epithelial cells. Currently, many clinical trials on HCQ prophylaxis in HCW are ongoing; these factors should be taken into account. Using higher doses of HCQ for prophylaxis is likely to be associated with increased safety concerns; thus, it may be worthwhile to focus on other possible interventions.
Highlights
COVID-19, the disease caused by the coronavirus SARS-CoV-2, continues to be an immense challenge for the scientific community throughout the world
The political attention and the controversies surrounding this drug have further fueled a debate in the scientific community over its potential as a chemoprophylactic agent against SARS-CoV-2 and for treatment of COVID-19
2 (Sbidian et al, 2020) Retrospective matched cohort study using Hospitalization due to COVID-19 occurred in Retrospective methodology
Summary
COVID-19, the disease caused by the coronavirus SARS-CoV-2, continues to be an immense challenge for the scientific community throughout the world. Due to the constraints of time, there has been much focus on the strategy of “drug repurposing/repositioning,” defined as identifying new uses of approved drugs that are outside the scope of their original medical indication (Ashburn and Thor, 2004). The 4aminoquinoline hydroxychloroquine (HCQ) and its congener chloroquine (CQ) have been repurposed for COVID-19 due to their proposed antiviral properties (Savarino et al, 2003). Reports of preclinical evidence of efficacy led to HCQ receiving unprecedented attention by the scientific community as well as by the lay public and media. The political attention and the controversies surrounding this drug have further fueled a debate in the scientific community over its potential as a chemoprophylactic agent against SARS-CoV-2 and for treatment of COVID-19
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