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Hydroxychloroquine

NOT Open Access | Groove Switching of Hydroxychloroquine Modulates the Efficacy of Binding and Induced Stability to DNA

June 22, 2021 - 14:08 -- NOT Open Access
Author(s): 
Sarkar S, Roy S, Singh PC
Reference: 
J Phys Chem B. 2021 Jun 17

Hydroxychloroquine (HCQ) is an important drug for the treatment of rheumatoid arthritis and malaria. HCQ targets specifically to nucleic acids for its action. However, the mechanism of HCQ binding and the effect of its binding on the stability of DNA are elusive. In this study, the binding mechanism of HCQ and the effect of binding on stability of different sequences of DNA have been investigated using spectroscopic and molecular dynamics (MD) simulation techniques. HCQ binds with all of the sequences of DNA and stabilizes them.

Not Open Access | Safety of treatment with chloroquine and hydroxychloroquine: A ten-year systematic review and meta-analysis

June 1, 2021 - 12:41 -- NOT Open Access
Author(s): 
Edington FLB, Gadellha SR, Santiago MB
Reference: 
Eur J Intern Med. 2021 Jun;88:63-72

To estimate the incidence rate ratio (IRR) of adverse events (AE) in chloroquine or hydroxychloroquine users.

NOT Open Access | Does hydroxychloroquine still have any role in the COVID-19 pandemic

March 17, 2021 - 16:58 -- NOT Open Access
Author(s): 
Schilling WH, White NJ
Reference: 
Expert Opin Pharmacother. 2021 Mar 16:1-10

The 4-aminoquinolines, chloroquine, and hydroxychloroquine have been used for over 70 years for malaria and rheumatological conditions, respectively. Their broad-spectrum antiviral activity, excellent safety profile, tolerability, low cost, and ready availability made them prime repurposing therapeutic candidates at the beginning of the COVID-19 pandemic.

Applying the CiPA Approach to Evaluate Cardiac Proarrhythmia Risk of some Antimalarials Used Off-label in the First Wave of COVID-19

February 25, 2021 - 09:44 -- Open Access
Author(s): 
Delaunois A, Abernathy M, Valentin JP, et al.
Reference: 
Clin Transl Sci. 2021 Feb 23

We applied a set of in silico and in vitro assays, compliant with the CiPA (Comprehensive In Vitro Proarrhythmia Assay) paradigm, to assess the risk of chloroquine or hydroxychloroquine-mediated QT prolongation and Torsades de Pointes (TdP), alone and combined with erythromycin and azithromycin, drugs repurposed during the first wave of COVID-19. Each drug or drug combination was tested in patch clamp assays on 7 cardiac ion channels, in in silico models of human ventricular electrophysiology (Virtual Assay® ) using control (healthy) or high-risk cell populations, and in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes.

Cardiotoxic Potential of Hydroxychloroquine, Chloroquine and Azithromycin in Adult Human Primary Cardiomyocytes

January 26, 2021 - 15:24 -- Open Access
Author(s): 
Jordaan P, Dumotier B, Traebert M, Miller PE, Ghetti A, Urban L, Abi-Gerges N
Reference: 
Toxicol Sci. 2021 Jan 23:kfaa194

Substantial efforts have been recently committed to develop COVID-19 medications, and Hydroxychloroquine alone or in combination with Azithromycin has been promoted as a repurposed treatment. While these drugs may increase cardiac toxicity risk, cardiomyocyte mechanisms underlying this risk remain poorly understood in humans. Therefore, we evaluated the pro-arrhythmia risk and inotropic effects of these drugs in the cardiomyocyte contractility-based model of the human heart. We found Hydroxychloroquine to have a low pro-arrhythmia risk, while Chloroquine and Azithromycin were associated with high risk.

Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2

January 20, 2021 - 07:00 -- Open Access
Author(s): 
Ou T, Mou H, Zhang L, Ojha A, Choe H, Farzan M
Reference: 
PLoS Pathog. 2021 Jan 19;17(1):e1009212

Hydroxychloroquine, used to treat malaria and some autoimmune disorders, potently inhibits viral infection of SARS coronavirus (SARS-CoV-1) and SARS-CoV-2 in cell-culture studies. However, human clinical trials of hydroxychloroquine failed to establish its usefulness as treatment for COVID-19. This compound is known to interfere with endosomal acidification necessary to the proteolytic activity of cathepsins. Following receptor binding and endocytosis, cathepsin L can cleave the SARS-CoV-1 and SARS-CoV-2 spike (S) proteins, thereby activating membrane fusion for cell entry.

Dose Optimization of Hydroxychloroquine for Coronavirus Infection 2019: Do Blood Concentrations Matter

January 5, 2021 - 15:18 -- Open Access
Author(s): 
Ippolito MM, Flexner C
Reference: 
Clin Infect Dis. 2020 Dec 31;71(11):2965-2967

Clinical trials of hydroxychloroquine (HCQ) for the treatment of coronavirus infection 2019 (COVID-19) are moving forward on the heels of conflicting, and sometimes controversial, observational studies out of China and France from the first months of the pandemic [1–3].

Liquid Chromatographic Methods for COVID-19 Drugs, Hydroxychloroquine and Chloroquine

December 23, 2020 - 08:49 -- Open Access
Author(s): 
Bilgin ZD, Evcil I, Yazgi D, Binay G, Okuyucu Genc C, Gulsen B, Huseynova A, Ozdemir AZ, Ozmen E, Usta Y, Ustun S, Caglar Andac S
Reference: 
J Chromatogr Sci. 2020 Dec 18:bmaa110

COVID-19 has been a threat throughout the world since December 2019. In attempts to discover an urgent treatment regime for COVID-19, hydroxychloroquine (HCQ) and chloroquine (CQ) have been on solidarity clinical trial. However, many countries have pulled HCQ and CQ from their COVID-19 treatment regimens recently, some countries still continue using them for patients who have previously started HCQ and CQ and they may complete their course under the supervision of a doctor. HCQ and CQ are 4-aminoquinoline drugs and it is safe to use them for autoimmune diseases, rheumatoid arthritis, systemic lupus erythematosus and malaria as well.

NOT Open Access | Metabolism and Interactions of Chloroquine and Hydroxychloroquine with Human Cytochrome P450 Enzymes and Drug Transporters

December 10, 2020 - 09:59 -- NOT Open Access
Author(s): 
Rendic SP, Guengerich FP
Reference: 
Curr Drug Metab. 2020 Dec 8

In clinical practice chloroquine and hydroxychloroquine are often co-administered with other drugs in the treatment of malaria, chronic inflammatory diseases, and COVID-19. Therefore, their metabolic properties and the effects on activity of cytochrome P450 (P450, CYP) enzymes and drug transporters should be considered into when developing the most efficient treatments for patients.

Systematic review of registered trials of Hydroxychloroquine prophylaxis for COVID-19 health-care workers at the first third of 2020

December 2, 2020 - 09:55 -- Open Access
Author(s): 
Bienvenu AL, Marty AM, Jones MK, Picot S
Reference: 
One Health. 2020 Dec;10:100141

In the absence of a vaccine the medical and scientific community is looking intensely at utilizing a pre or post exposure drug that could decrease viremia. The search for a medication that could reduce risk of serious disease, and ideally of any manifestation of disease from SARS-CoV2, and of asymptomatic shedding of SARS-CoV2 is of urgent interest. Repurposing existing pharmaceuticals is among the approaches to achieve these ends.

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