Hydroxychloroquine in COVID-19: Potential Mechanism of Action Against SARS-CoV-2

Abstract

Purpose of Review The rapid spread of virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has turned out to be a global emergency. Symptoms of this viral infection, coronavirus disease 2019 (COVID-19), include mild infections of the upper respiratory tract, viral pneumonia, respiratory failure, multiple organ failure and death. Till date, no drugs have been discovered to treat COVID-19 patients, and therefore, a considerable amount of interest has been shown in repurposing the existing drugs. Recent Findings Out of these drugs, chloroquine (CQ) and hydroxychloroquine (HCQ) have demonstrated positive results indicating a potential antiviral role against SARS-CoV-2. Its mechanism of action (MOA) includes the interference in the endocytic pathway, blockade of sialic acid receptors, restriction of pH mediated spike (S) protein cleavage at the angiotensin-converting enzyme 2 (ACE2) binding site and prevention of cytokine storm. Unfortunately, its adverse effects like gastrointestinal complications, retinopathy and QT interval prolongation are evident in treated COVID-19 patients. Yet, multiple clinical trials have been employed in several countries to evaluate its ability in turning into a needed drug in this pandemic. Summary This review attempts to summarize the MOA of CQ/HCQ and its side effects. The existing literature hints that till date, the role of CQ/HCQ in COVID-19 may be sceptical, and further studies are warranted for obtaining a therapeutic option that could be effectively used across the world to rise out from this pandemic.

COVID-19 and diabetes mellitus: from pathophysiology to clinical management

“…The antimalaria drugs chloroquine and hydroxychloroquine have been used to treat SARS-CoV-2 infection despite their potential adverse effects 175 , 176 . The two main mechanisms of action of hydroxychloroquine are believed to be via its restriction of viral spike protein cleavage at the ACE2 binding site, and its anti-inflammatory and immunomodulatory properties 177 . Hydroxychloroquine also has glucose-lowering efficacy by increasing insulin sensitivity and improving pancreatic β-cell function 178 , which has enabled hydroxychloroquine to be prescribed as an antidiabetic medication in some countries 179 .…”

JAK-STAT Pathway Inhibition and their Implications in COVID-19 Therapy

“…It contains a single strand of a positive-sense RNA genome with 29,903 base pairs [ 61 ]. The viral RNA is enclosed in an enveloped structure and when viewed under an electron microscope, appears as a crown-like structure due to the incorporation of structural spike proteins on its outer surface that facilitates its entry, proliferation, and infectivity in host cells via ACE2 receptors [ 62 , 63 ]. The ACE2 receptors are expressed in epithelial cells of the kidney, heart lungs, and blood vessel endothelial cells.…”

Prevention and treatment of COVID-19: Focus on interferons, chloroquine/hydroxychloroquine, azithromycin, and vaccine

“…The action of CQ and HCQ may be different depending on the type of microorganisms, but it is shown that it targets the interaction between the SARS-CoV and its receptor by hampering the glycosylation of its cellular receptors blocking the SARS-CoV infections [ 125 ]. Besides, CQ/HCQ blocks the sialic acid receptors, thus preventing the entry of SARS-CoV-2 into the upper respiratory tract [ 126 ]. Furthermore, CQ has an immunomodulatory ability on activated immune cells [ 11 , 127 ].…”