Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, India.
IIT-Bombay Monash Academy, Indian Institute of Technology Bombay, Mumbai 400076, India.
J Med Chem. 2023 Nov 9;66(21):14411-14433. doi: 10.1021/acs.jmedchem.3c01238. Epub 2023 Oct 29.
The COVID-19 pandemic ignited research centered around the identification of robust biomarkers and therapeutic targets. SARS-CoV-2, the virus responsible, hijacks the metabolic machinery of the host cells. It relies on lipids and lipoproteins of host cells for entry, trafficking, immune evasion, viral replication, and exocytosis. The infection causes host cell lipid metabolic remodelling. Targeting lipid-based processes is thus a promising strategy for countering COVID-19. Here, we review the role of lipids in the different steps of the SARS-CoV-2 pathogenesis and identify lipid-centric targetable avenues. We discuss lipidome changes in infected patients and their relevance as potential clinical diagnostic or prognostic biomarkers. We summarize the emerging direct and indirect therapeutic approaches for targeting COVID-19 using lipid-inspired approaches. Given that viral protein-targeted therapies may become less effective due to mutations in emerging SARS-CoV-2 variants, lipid-inspired interventions may provide additional and perhaps better means of combating this and future pandemics.
COVID-19 大流行引发了围绕鉴定强大生物标志物和治疗靶点的研究。导致 COVID-19 的病毒 SARS-CoV-2 劫持宿主细胞的代谢机制。它依赖宿主细胞的脂质和脂蛋白进入、运输、免疫逃逸、病毒复制和胞吐。感染导致宿主细胞脂质代谢重排。因此,针对基于脂质的过程是对抗 COVID-19 的有前途的策略。在这里,我们回顾了脂质在 SARS-CoV-2 发病机制的不同步骤中的作用,并确定了以脂质为中心的可靶向途径。我们讨论了感染患者的脂质组变化及其作为潜在临床诊断或预后生物标志物的相关性。我们总结了使用脂质启发方法针对 COVID-19 的新兴直接和间接治疗方法。鉴于新出现的 SARS-CoV-2 变体的突变可能使病毒蛋白靶向治疗效果降低,因此基于脂质的干预措施可能为对抗这种疾病和未来的大流行提供额外的、或许更好的手段。