Hypoxia, HIF-1α, and COVID-19: from pathogenic factors to potential therapeutic targets

• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2020,（12）
• 所属期刊栏目: Review Article
• 页码范围: 1539-1546
• 页数: 8页
• 语种: 英文

摘要

The pandemic of coronavirus disease 2019 (COVID-19) and its pathogen,severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the greatest current threat to global public health.The highly infectious SARS-CoV-2 virus primarily attacks pulmonary tissues and impairs gas exchange leading to acute respiratory distress syndrome (ARDS) and systemic hypoxia.The current pharmacotherapies for COVID-19 largely rely on supportive and anti-thrombi treatment and the repurposing of antimalarial and antiviral drugs such as hydroxychloroquine and remdesivir.For a better mechanistic understanding of COVID-19,our present review focuses on its primary pathophysiologic features: hypoxia and cytokine storm,which are a prelude to multiple organ failure and lethality.We discussed a possible link between the activation of hypoxia inducible factor 1α (HIF-1α) and cell entry of SARS-CoV-2,since HIF-1α is shown to suppress the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2 (TMPRSS2) and upregulate disintegrin and metalloproteinase domain-containing protein 17 (ADAM17).In addition,the protein targets of HIF-1cα are involved with the activation of pro-inflammatory cytokine expression and the subsequent inflammatory process.Furthermore,we hypothesized a potential utility of so-called "hypoxic conditioning" to activate HIF-1α-induced cytoprotective signaling for reduction of illness severity and improvement of vital organ function in patients with COVID-19.Taken together,we would propose further investigations into the hypoxia-related molecular mechanisms,from which novel targeted therapies can be developed for the improved management of COVID-19.