Pharmacokinetics and Pharmacological Properties of Chloroquine and Hydroxychloroquine in the Context of COVID‐19 Infection (original) (raw)
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Medical Journal of the Islamic Republic of Iran, 2020
Background: The world is facing a pandemic of COVID-19, a respiratory disease caused by a novel coronavirus which is now called SARS-CoV-2. Current treatment recommendations for the infection are mainly repurposed drugs based on experience with other clinically similar conditions and are not backed by direct evidence. Chloroquine (CQ) and its derivative Hydroxychloroquine (HCQ) are among the candidates. We aimed to synthesize current evidence systematically for in vitro, animal, and human studies on the efficacy and safety of chloroquine in patients with COVID-19. Methods: The Cochrane Library, Google Scholar, PubMed (via Medline), Embase, Scopus, and Web of Science, MedRxiv, clinical trial registries including clinicaltrials.gov, ChiCTR (Chinese Clinical Trial Registry), IRCT (Iranian Registry of Clinical Trials), and the EU Clinical Trials Register. We used the Cochrane tool for risk of bias assessment in randomized studies, the ROBINS tool for non-randomized studies, and the GRAD...
Hydroxychloroquine in COVID-19: Potential Mechanism of Action Against SARS-CoV-2
Current Pharmacology Reports, 2020
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. 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, retin...
Chloroquine and hydroxychloroquine in the treatment of COVID-19: the never-ending story
Applied Microbiology and Biotechnology
The anti-malarial drugs chloroquine (CQ) and hydroxychloroquine (HCQ) have been suggested as promising agents against the new coronavirus SARS-CoV-2 that induces COVID-19 and as a possible therapy for shortening the duration of the viral disease. The antiviral effects of CQ and HCQ have been demonstrated in vitro due to their ability to block viruses like coronavirus SARS in cell culture. CQ and HCQ have been proposed to reduce immune reactions to infectious agents, inhibit pneumonia exacerbation, and improve lung imaging investigations. CQ analogs have also revealed the anti-inflammatory and immunomodulatory effects in treating viral infections and related ailments. There was, moreover, convincing evidence from early trials in China about the efficacy of CQ and HCQ in the anti-COVID-19 procedure. Since then, research and studies have been massive to ascertain these drugs' efficacy and safety in treating the viral disease. In the present review, we construct a synopsis of the main properties and current data concerning the metabolism of CQ/HCQ, which were the basis of assessing their potential therapeutic roles against the new coronavirus infection. The effective role of QC and HCQ in the prophylaxis and therapy of COVID-19 infection is discussed in light of the latest international medical-scientific research results. Key points • Data concerning metabolism and properties of CQ/HCQ are discussed. • The efficacy of CQ/HCQ against COVID-19 has been the subject of contradictory results. • CQ/HCQ has little or no effect in reducing mortality in SARS-CoV-2-affected patients.
Nature Communications
Here, we randomized 53 patients hospitalized with coronavirus disease 2019 (COVID-19) to hydroxychloroquine therapy (at a dose of 400 mg twice daily for seven days) in addition to standard care or standard care alone (ClinicalTrials.gov Identifier, NCT04316377). All severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients 18 years of age or older were eligible for study inclusion if they had moderately severe COVID-19 at admission. Treatment with hydroxychloroquine did not result in a significantly greater rate of decline in SARS-CoV-2 oropharyngeal viral load compared to standard care alone during the first five days. Our results suggest no important antiviral effect of hydroxychloroquine in humans infected with SARS-CoV-2.
Journal of National Black Nurses' Association : JNBNA, 2020
Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and associated coronavirus disease 19 (COVID-19) began ravaging most of the globe in November 2019. In the United States more than 25 million people have been infected with SARS-CoV-2. To date, COVID-19 has killed close to 400,000 U.S. citizens. In the face of limited pharmacotherapies, the current burden of SARS-CoV-2 and COVID-19 signals overwhelming sickness and trillions in healthcare costs ahead. The need to expeditiously identify safe and efficacious prophylaxis and treatment options is critical. Drug repositioning may be a promising strategy toward mitigating the impact of SARS-CoV-2 and COVID-19. This rapid review appraises available evidence on the viability of vintage antimalarial drugs chloroquine (CHQ) and its analog hydroxychloroquine (HCQ) repositioned for SARS-CoV-2 prophylaxis and COVID-19 treatment. Findings suggest neither the use of CHQ nor HCQ singularly, or concomitantly, with azithromycin and/or...
Medicine in Drug Discovery, 2021
Recently, the pandemic outbreak of a novel coronavirus, officially termed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), indicated by a pulmonary infection in humans, has become one of the most significant challenges for public health. In the current fight against coronavirus disease-2019, the medical and health authorities across the world focused on quick diagnosis and isolation of patients; meanwhile, researchers worldwide are exploring the possibility of developing vaccines and novel therapeutic options to combat this deadly disease. Recently, based on various small clinical observations, uncontrolled case studies and previously reported antiviral activity against SARS-CoV-1 chloroquine (CQ) and hydroxychloroquine (HCQ) have attracted exceptional consideration as possible therapeutic agents against SARS-CoV-2. However, there are reports on little to no effect of CQ or HCQ against SARS-CoV-2, and many reports have raised concerns about their cardiac toxicity. Here, in this review, we examine the chemistry, molecular mechanism, and pharmacology, including the current scenario and future prospects of CQ or HCQ in the treatment of SARS-CoV-2.
Informatics in Medicine Unlocked, 2020
Chloroquine (CQ) and hydroxychloroquine (HCQ) are undergoing several clinical trials for evaluating their efficacy and safety as antiviral drugs. Yet, there is still a great debate about their efficacy in combating COVID-19. This study aimed to evaluate the feasibility of intranasal and/or pulmonary administration of CQ/HCQ for COVID-19 using Bio/chemoinformatics tools. We, hereby, hypothesize the success of the intranasal and the pulmonary routes through a gelatin matrix to overcome several challenges related to CQ and HCQ pharmacodynamics and pharmacokinetics properties and to increase their local concentrations at the sites of initial viral entry while minimizing the potential side effects. Molecular docking on the gelatin-simulated matrix demonstrated high loading values and a sustained release profile. Moreover, the docking on mucin as well as various receptors including Angiotensin-converting enzyme 2 (ACE-2), heparin sulphate proteoglycan and Phosphatidylinositol binding clathrin assembly protein (PICALM), which are expressed in the lung and intranasal tissues and represent initial sites of attachment of the viral particles to the surface of respiratory cells, has shown good binding of CQ and HCQ to these receptors. The presented data provide an insight into the use of a novel drug formulation that needs to be tested in adequately powered randomized controlled clinical trials; aiming for a sustained prophylaxis effect and/or a treatment strategy against this pandemic viral infection.
Human Immune Response to COVID-19 Infection and Potential Role of Chloroquine Family of Drugs
2020
Currently, world is witnessing a massive morbidity and mortality due to COVID-19 pandemic. A novel strain of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The virus enters inside the body and infect the cells through angiotensin-converting enzyme 2 (ACE2) receptor. The S1 protein of SARS-CoV-2 binds to the ACE2 receptor which results in endocytosis and transfer of virus into endosomes of body cells. Entry of SARS-CoV-2 results in activation of innate immune responses first followed by adaptive immune responses. The effective host immune responses are crucial to control and prevent viral infection. However, excessive production of proinflammatory cytokines and decrease in number of T-lymphocytes are the major reasons associated with severity of COVID-19. Therapies and drugs that can modulate the immune responses appropriately may play a crucial role to control and prevent the progression of disease. Chloro...