Hydroxychloroquine: An old drug with new relevance

Shippey, Eugen Alexander; Wagler, Vanya D.; Collamer, Angelique N.

doi:10.3949/ccjm.85a.17034

Cited by 111 publications

(107 citation statements)

References 49 publications

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“…After quinacrine was introduced as an antimalarial agent in World War II, it has associated with yellowish discoloration of the skin and other side effects. As a result of quinacrine-associated adverse effects, other antimalarial agents including chloroquine and hydroxychloroquine (HCQ) were derived with extensive chemical modification [9]. HCQ is an older drug and still used in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Potential Effect of Hydroxychloroquine in Diabetes Mellitus: A Systematic Review on Preclinical and Clinical Trial Studies

Wondafrash

Desalegn

Yimer

et al. 2020

Journal of Diabetes Research

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Background. Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia. It affects millions of people globally. In spite of many antidiabetic drugs that are available, an adequate level of control remains challenging. Hydroxychloroquine is an immunomodulatory drug that has been used for the treatment of malaria and autoimmune diseases. There is an emerging evidence that suggests its beneficial effect against diabetes mellitus. Therefore, this systematic review is aimed at discoursing the role of hydroxychloroquine against diabetes mellitus and its potential mechanisms of actions. Methods. A systematic and manual searching was carried out to retrieve relevant articles (preclinical and clinical studies) published from January 2014 to July 2019. Electronic databases including PubMed and Scopus as well as clinicaltrials.gov have been searched using different searching terms: “hydroxychloroquine,” “diabetes mellitus,” “hyperglycemia,” and “insulin resistance.” The MeSH terms (PubMed) and text words were combined with “AND” or “OR.” In addition, manual searching of Google Engine and Google Scholar was conducted. Quality assessment of all the included studies was performed using CAMARADES (preclinical studies) and the Newcastle-Ottawa Scale and Cochrane Collaboration’s tools (clinical studies). Results. A total of eighteen studies (three experimental and fifteen clinical studies) were found to be eligible for the present systematic review. Among the included clinical studies (six randomized control trials, five observational studies, and four cohort studies), about 55,776 study participants were involved. Most of these studies showed significant improvement of lipid profile and insulin levels and substantial diminution of hemoglobin A1c, fasting plasma glucose, and postprandial blood glucose levels. Reduction in lysosomal degradation of the internal insulin-insulin receptor complex and enhancement in insulin sensitivity and adiponectin levels are some of the hypothesized mechanisms for the antidiabetic effect of hydroxychloroquine. Conclusion. The current review provides preliminary evidence for potential antidiabetic properties of hydroxychloroquine. Though the provided available data were promising, further clinical trials and mechanistic studies are needed to determine its long-term effects.

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Section: Introductionmentioning

confidence: 99%

Potential Effect of Hydroxychloroquine in Diabetes Mellitus: A Systematic Review on Preclinical and Clinical Trial Studies

Wondafrash

Desalegn

Yimer

et al. 2020

Journal of Diabetes Research

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“…Hydroxychloroquine (HCQ) is an antimalarial drug which is also used to treat rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus (SLE). It is derived from chloroquine and has been in use for over 60 years [42]. Its definite mechanism of action has yet to be elucidated but it appears to work through different pathways, inducing anti-inflammatory, anti-oxidant and anti-thrombotic effects [21].…”

Section: Administration Of Hydroxychloroquine In Pregnancymentioning

confidence: 99%

Hydroxychloroquine as a Preventive and Therapeutic Option in Preeclampsia – a Literature Review

Deharde

Klockenbusch

Schmitz

et al. 2020

Geburtshilfe Frauenheilkd

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Preeclampsia is one of the most feared complications of pregnancy and puerperium and represents a serious threat to mother and child. In addition, a history of preeclampsia increases the risk of future cardiovascular events. New diagnostic and therapeutic approaches are needed. New therapeutic options are currently being discussed, one of which is the administration of hydroxychloroquine. It is an antimalarial drug which is also used to treat rheumatological disease and its use in pregnancy is considered safe. A reduced incidence of preeclampsia in patients with selected rheumatological disorders after administration of hydroxychloroquine has already been shown; however, the case numbers are very low. Neither the full pathogenesis of preeclampsia nor the exact modes of action of hydroxychloroquine have been completely elucidated, but there are several common features which make hydroxychloroquine a promising option for the prevention and treatment of preeclampsia. Further research, especially prospective, randomized controlled trials, is needed to prove its efficacy. This review discusses the pathogenesis of preeclampsia and gives an overview of new options for its prevention and treatment, including the administration of hydroxychloroquine in pregnancy.

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“…Hydroxychloroquine is an aminoquinoline-like chloroquine (Furst, 1996). It is a drug commonly prescribed for the treatment of uncomplicated malaria, rheumatoid arthritis, chronic discoid lupus erythematosus, and systemic lupus erythematosus (Shippey et al, 2018). Chloroquine and hydroxychloroquine are being investigated for the treatment of SARS-CoV-2 (Devaux et al, 2020), and they have been reported to have direct antiviral effects, such as inhibition of flaviviruses, retroviruses (like HIV), and many coronaviruses.…”

Section: Discussionmentioning

confidence: 99%

<strong>Computational Screening for Potential Drug Candidates Against SARS-CoV-2 Main Protease</strong>

Andrade¹,

Ghosh²,

Barh³

et al. 2020

Preprint

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Background: SARS-CoV-2 that are the causal agent of a current pandemic are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly and pathogenicity. The ~33.8KDa Mpro protease of SARS-CoV-2 is a non-human homologue and highly conserved among several coronaviruses indicating Mpro could be a potential drug target for Coronaviruses.Methods: Here we performed computational ligand screening of four pharmacophores (OEW, Remdesivir, Hydroxycholoquine and N3) that are presumed to have positive effects against SARS-CoV-2 Mpro protease (6LU7) and also screened 50,000 molecules from the ZINC Database dataset against this protease target.Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 10 best selected ligands namely, ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as β-carboline, Alkaloids and Polyflavonoids, and all of them displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as with other known ligands.Conclusion: Our results suggest that these 10 molecules could be effective against SARS-CoV-2 protease and may be tested in vitro and in vivo to develop novel drugs against this virus.

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Hydroxychloroquine: An old drug with new relevance

Cited by 111 publications

References 49 publications

Potential Effect of Hydroxychloroquine in Diabetes Mellitus: A Systematic Review on Preclinical and Clinical Trial Studies

Potential Effect of Hydroxychloroquine in Diabetes Mellitus: A Systematic Review on Preclinical and Clinical Trial Studies

Hydroxychloroquine as a Preventive and Therapeutic Option in Preeclampsia – a Literature Review

<strong>Computational Screening for Potential Drug Candidates Against SARS-CoV-2 Main Protease</strong>

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