Pharmacogenomic considerations for repurposing of dexamethasone as a potential drug against SARS-CoV-2 infection.

IF 1.7 4区医学 Q3 PHARMACOLOGY & PHARMACY

Personalized medicine Pub Date : 2021-07-01 Epub Date: 2021-06-04 DOI:10.2217/pme-2020-0183

Manik Vohra, Anu Radha Sharma, Kapaettu Satyamoorthy, Padmalatha S Rai

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引用次数: 14

Abstract

Immunomodulatory and analgesic effects of dexamethasone are clinically well established, and this synthetic corticosteroid acts as an agonist of glucocorticoid receptors. Early results of the RECOVERY Trial from the United Kingdom and others suggest certain benefits of dexamethasone against COVID-19 chronic patients. The efforts have been acknowledged by World Health Organization with an interim guideline to use in patients with a severe and critical illness. The inherent genetic variations in genes such as CYP3A5, NR3C1, NR3C2, etc., involved in the pharmacokinetic and pharmacodynamic processes may influence dexamethasone's effects as an anti-inflammatory drug. Besides, the drug may influence transcriptome or metabolic changes in the individuals. In the present review, we summarize the reported genetic variations that impact dexamethasone response and discuss dexamethasone-induced changes in transcriptome and metabolome that may influence potential treatment outcome against COVID-19.

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重新利用地塞米松作为对抗SARS-CoV-2感染的潜在药物的药物基因组学考虑。

地塞米松的免疫调节和镇痛作用在临床上得到了很好的证实，这种合成的皮质类固醇可作为糖皮质激素受体的激动剂。来自英国和其他国家的康复试验的早期结果表明，地塞米松对COVID-19慢性患者有一定的益处。这些努力得到了世界卫生组织的认可，并制定了一项用于重症和危重症患者的临时指南。参与药代动力学和药效学过程的CYP3A5、NR3C1、NR3C2等基因的内在遗传变异可能影响地塞米松的抗炎作用。此外，药物可能影响个体的转录组或代谢变化。在本综述中，我们总结了已报道的影响地塞米松反应的遗传变异，并讨论了地塞米松诱导的转录组和代谢组的变化，这些变化可能影响对COVID-19的潜在治疗结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Personalized medicine 医学-药学

CiteScore

3.30

自引率

4.30%

发文量

审稿时长

6-12 weeks

期刊介绍： Personalized Medicine (ISSN 1741-0541) translates recent genomic, genetic and proteomic advances into the clinical context. The journal provides an integrated forum for all players involved - academic and clinical researchers, pharmaceutical companies, regulatory authorities, healthcare management organizations, patient organizations and others in the healthcare community. Personalized Medicine assists these parties to shape thefuture of medicine by providing a platform for expert commentary and analysis. The journal addresses scientific, commercial and policy issues in the field of precision medicine and includes news and views, current awareness regarding new biomarkers, concise commentary and analysis, reports from the conference circuit and full review articles.