Lipid homeostasis and mevalonate pathway in COVID-19: Basic concepts and potential therapeutic targets

IF 14 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research Pub Date : 2021-04-01 DOI:10.1016/j.plipres.2021.101099

Maria Chiara Proto , Donatella Fiore , Chiara Piscopo , Cristina Pagano , Mario Galgani , Sara Bruzzaniti , Chiara Laezza , Patrizia Gazzerro , Maurizio Bifulco

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引用次数: 19

Abstract

Despite encouraging progresses achieved in the management of viral diseases, efficient strategies to counteract infections are still required. The current global challenge highlighted the need to develop a rapid and cost-effective strategy to counteract the SARS-CoV-2 pandemic.

Lipid metabolism plays a crucial role in viral infections. Viruses can use the host lipid machinery to support their life cycle and to impair the host immune response. The altered expression of mevalonate pathway-related genes, induced by several viruses, assures survival and spread in host tissue. In some infections, statins, HMG-CoA-reductase inhibitors, reduce cholesterol in the plasma membrane of permissive cells resulting in lower viral titers and failure to internalize the virus. Statins can also counteract viral infections through their immunomodulatory, anti-inflammatory and anti-thrombotic effects. Beyond statins, interfering with the mevalonate pathway could have an adjuvant effect in therapies aimed at mitigating endothelial dysfunction and deregulated inflammation in viral infection.

In this review we depicted the historical and current evidence highlighting how lipid homeostasis and mevalonate pathway targeting represents a valid approach to rapidly neutralize viruses, focusing our attention to their potential use as effective targets to hinder SARS-CoV-2 morbidity and mortality.

Pros and cons of statins and Mevalonate-pathway inhibitors have been also dissected.

Abstract Image

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COVID-19的脂质稳态和甲羟戊酸途径:基本概念和潜在的治疗靶点

尽管在病毒性疾病管理方面取得了令人鼓舞的进展，但仍然需要有效的战略来对抗感染。当前的全球挑战突出表明，需要制定一项快速和具有成本效益的战略，以应对SARS-CoV-2大流行。脂质代谢在病毒感染中起关键作用。病毒可以利用宿主的脂质机制来支持它们的生命周期，并削弱宿主的免疫反应。几种病毒诱导甲羟戊酸途径相关基因表达的改变，保证了宿主组织的生存和传播。在某些感染中，他汀类药物、hmg -辅酶a还原酶抑制剂可降低允许细胞质膜中的胆固醇，导致病毒滴度降低，病毒无法内化。他汀类药物还可以通过免疫调节、抗炎和抗血栓作用来对抗病毒感染。除他汀类药物外，干扰甲羟戊酸途径可能在旨在减轻内皮功能障碍和病毒感染中不受调节的炎症的治疗中具有辅助作用。在这篇综述中，我们描述了历史和当前的证据，强调脂质稳态和甲羟戊酸途径靶向是如何快速中和病毒的有效方法，并将我们的注意力集中在它们作为抑制SARS-CoV-2发病率和死亡率的有效靶点的潜在应用上。他汀类药物和甲羟戊酸途径抑制剂的利弊也已被剖析。

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

Progress in lipid research 生物-生化与分子生物学

CiteScore

24.50

自引率

2.20%

发文量

审稿时长

14.6 weeks

期刊介绍： The significance of lipids as a fundamental category of biological compounds has been widely acknowledged. The utilization of our understanding in the fields of biochemistry, chemistry, and physiology of lipids has continued to grow in biotechnology, the fats and oils industry, and medicine. Moreover, new aspects such as lipid biophysics, particularly related to membranes and lipoproteins, as well as basic research and applications of liposomes, have emerged. To keep up with these advancements, there is a need for a journal that can evaluate recent progress in specific areas and provide a historical perspective on current research. Progress in Lipid Research serves this purpose.