Repurposing Chloroquine Against Multiple Diseases With Special Attention to SARS-CoV-2 and Associated Toxicity

Kamat, Siya; Kumari, Madhuree

doi:10.3389/fphar.2021.576093

Cited by 21 publications

(16 citation statements)

References 177 publications

(125 reference statements)

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“…The intense discussion of HCQ as a cause for psychosis is contrasted by some recent papers, which prove the relative safety of HCQ. Even for CQ, which is generally more fraught with side effects due to a longer elimination half time and greater penetration through the BBB (Hamm & Rosenthal, 2020;Kamat & Kumari, 2021), an increased risk for psychosis (Papazisis et al, 2021) has not always been found (Sato et al, 2020), and analyses of various data bases found no increased risk for HCQ (Garcia et al, 2020;Lane et al, 2020;Edington et al, 2021;Papazisis et al, 2021). The warning regarding the risk of psychosis seems to be based on a handful of case reports which have accumulated during the long use of this drug (Emmanuel & Östlundh, 2020;Juurlink, 2020).…”

Section: Discussionmentioning

confidence: 99%

First-episode psychotic disorders in the wake of the COVID-19 pandemic: a descriptive review of casereports

Rittmannsberger¹,

Barth²,

Malík³

et al. 2022

Acta Neuropsychiatr.

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Objective: Since the onset of COVID-19 pandemic many case reports and case series dealt with new onset psychotic disorders in patients either infected with SARS-CoV-2 or thematically linked to the pandemic, but without an infection. Our aim was to provide a comprehensive collection of these reports to illustrate the nature of these psychoses. Methods: We conducted a literature search in Medline, EMBASE, PSYCHINFO, using search terms regarding first episode psychotic disorders in the context of corona. Results: 96 case reports or case series covering 146 patients (62 without and 84 with SARS-CoV-2 infection) were found. Compared to patients without infection, patients with infection showed significantly more often visual hallucinations (28.6% vs 8.1%), confusion (36.9% vs 11.3%), an acute onset of illness (88.5% vs 59.6%) and less often depression (13.1% vs 35.5%) and a delusional content related to the pandemic (29.5% vs 78.3%). Both groups had an equally favourable outcome with a duration of psychosis ≤2 weeks in half and full remission in two thirds of patients. In patients with infection signs of inflammation were reported in 78.3% and increased CRP in 58.6%. While reports on patients with infection are continuously published, no report about patients without infection was found after July 2020. Conclusion: Cases without infection were considered reactive and originated all from the first wave of the Corona pandemic. In cases with infection, inflammation was considered as the main pathogenetic factor but was not found in all patients. Diagnosis was impeded by the overlap of psychosis with delirium.

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Section: Discussionmentioning

confidence: 99%

First-episode psychotic disorders in the wake of the COVID-19 pandemic: a descriptive review of casereports

Rittmannsberger¹,

Barth²,

Malík³

et al. 2022

Acta Neuropsychiatr.

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“…CQ/HCQ was quickly introduced to treat people suffering from severe COVID-19 [ 6 , 65 ], however its exact effects have not yet been published. Our computer simulations have revealed that permanent and transient treatment with CQ/HCQ could affect the level of SARS-CoV-2 in the host cell ( Fig 4 ).…”

Section: Discussionmentioning

confidence: 99%

Chloroquine and COVID-19—A systems biology model uncovers the drug’s detrimental effect on autophagy and explains its failure

Kapuy

Korcsmáros

2022

PLoS ONE

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The COVID-19 pandemic caused by SARS-CoV-2 has resulted in an urgent need for identifying potential therapeutic drugs. In the first half of 2020 tropic antimalarial drugs, such as chloroquine (CQ) or hydroxochloroquine (HCQ) were the focus of tremendous public attention. In the initial periods of the pandemic, many scientific results pointed out that CQ/HCQ could be very effective for patients with severe COVID. While CQ and HCQ have successfully been used against several diseases (such as malaria, autoimmune disease and rheumatic illnesses); long term use of these agents are associated with serious adverse effects (i.e. inducing acute kidney injury, among many others) due to their role in blocking autophagy-dependent self-degradation. Recent experimental and clinical trial data also confirmed that there is no sufficient evidence about the efficient usage of CQ/HCQ against COVID-19. By using systems biology techniques, here we show that the cellular effect of CQ/HCQ on autophagy during endoplasmic reticulum (ER) stress or following SARS-CoV-2 infection results in upregulation of ER stress. By presenting a simple mathematical model, we claim that although CQ/HCQ might be able to ameliorate virus infection, the permanent inhibition of autophagy by CQ/HCQ has serious negative effects on the cell. Since CQ/HCQ promotes apoptotic cell death, here we confirm that addition of CQ/HCQ cannot be really effective even in severe cases. Only a transient treatment seemed to be able to avoid apoptotic cell death, but this type of therapy could not limit virus replication in the infected host. The presented theoretical analysis clearly points out the utility and applicability of systems biology modelling to test the cellular effect of a drug targeting key major processes, such as autophagy and apoptosis. Applying these approaches could decrease the cost of pre-clinical studies and facilitate the selection of promising clinical trials in a timely fashion.

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“…Later on, studies proved decreased in-hospital survival and increased frequency of ventricular arrhythmias in hospitalized patients. Hence, the trial with these drugs was suspended and WHO notified that HCQ has no beneficial effect and discontinued its use for COVID-19 infection with immediate effect [ 45 , 47 – 49 ].…”

Section: Main Textmentioning

confidence: 99%

Potent phytochemicals against COVID-19 infection from phyto-materials used as antivirals in complementary medicines: a review

2021

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Background Following the outbreak of the COVID-19 pandemic, there was a surge of research activity to find methods/drugs to treat it. There has been drug-repurposing research focusing on traditional medicines. Concomitantly, many researchers tried to find in silico evidence for traditional medicines. There is a great increase in article publication to commensurate the new-found research interests. This situation inspired the authors to have a comprehensive understanding of the multitude of publications related to the COVID-19 pandemic with a wish to get promising drug leads. Main body This review article has been conceived and made as a hybrid of the review of the selected papers advertised recently and produced in the interest of the COVID-19 situation, and in silico work done by the authors. The outcome of the present review underscores a recommendation for thorough MDS analyses of the promising drug leads. The inclusion of in silico work as an addition to the review was motivated by a recently published article of Toelzer and colleagues. The in silico investigation of free fatty acids is novel to the field and it buttresses the further MDS analysis of drug leads for managing the COVID-19 pandemic. Conclusion The review performed threw light on the need for MDS analyses to be considered together with the application of other in silico methods of prediction of pharmacologic properties directing towards the sites of drug-receptor regulation. Also, the present analysis would help formulate new recipes for complementary medicines.

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Repurposing Chloroquine Against Multiple Diseases With Special Attention to SARS-CoV-2 and Associated Toxicity

Cited by 21 publications

References 177 publications

First-episode psychotic disorders in the wake of the COVID-19 pandemic: a descriptive review of casereports

First-episode psychotic disorders in the wake of the COVID-19 pandemic: a descriptive review of casereports

Chloroquine and COVID-19—A systems biology model uncovers the drug’s detrimental effect on autophagy and explains its failure

Potent phytochemicals against COVID-19 infection from phyto-materials used as antivirals in complementary medicines: a review

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