Role of HIF 1 α in Covid-19 Disease

Acta Scientific NUTRITIONAL HEALTH (ISSN:2582-1423) Volume 5 Issue 6 June 2021 Review Article Role of HIF 1 α in Covid-19 Disease Tulsi Patil1*, Arun Soni2, Chirag Patel3 and Sanjeev Acharya2 1 Research Scholar, SSR College of Pharmacy, UT of Dadra and Nagar Haveli, India 3 SSR College of Pharmacy, UT of Dadra and Nagar Haveli, India 2 L. M. College of Pharmacy, Ahmedabad, India *Corresponding Author: Tulsi Patil, Research Scholar, SSR College of Pharmacy, UT Received: April 28, 2021 Published: May 24, 2021 © All rights are reserved by Tulsi Patil., et al. of Dadra and Nagar Haveli, India. Abstract This review article aims to point out the many roles of HIF-1α in COVID-19 diseases. World health organization named the newly emerged virus SARS-CoV-2 or 2019-nCoV or covid-19. At beginning of coronavirus symptoms of pneumonia were appeared in December 2019 near Wuhan city of China. The Coronavirus Disease 2019 outbreak spread rapidly worldwide and is associated with the high death rate in humans. However, there are currently fewer safe and effective drugs available for targeting SARS-CoV-2. So, there is an emergency for the invention of effective prevention and treatment options for the SARS-CoV-2 outbreak. SARS-CoV-2 recognizes the human ACE2 more strongly than SARS-CoV. SARS-CoV-2 spike supermolecule having a very high robust binding affinity to human ACE2. Relatively limited information is understood about the transcriptional regulation of ACE2. Hypoxic condition reduces the syn- thesis of ACE2, Further experimentation has shown that hypoxic condition induced HIF-1α protein leads to increases ACE synthesis which, prompts to rise the amount of Ang II and overall this process modulates the reduction in ACE2 synthesis with the help of Ang II. Activation of HIF-1 is related to numerous physiological and pathological processes. HIF-1 will manage ACE2 regulation and several natural components exhibit the role in activation and stabilization of the HIF-1α protein. The level of HIF-1α in cells gives us future opportunities for new, safe, and effective treatment options for the novel coronavirus. Keywords: COVID-19; SARS-COV; HIF-1α Pathway; Influenza A Virus; Natural HIF-1α Activators Introduction World health organization named the newly emerged virus SARS-CoV-2 or 2019-nCoV or covid-19. At beginning of corona- virus symptoms of pneumonia were appeared in December 2019 between the HIF-1 α and SARS-CoV-2, therefore HIF-1 will manage ACE2 regulation. Synthetic as well as naturally occurring HIF-1 alpha activators may show a promising effect in COVID-19. HIF-1 (Hypoxia-inducible factor) is a fundamental protein of hu- near Wuhan city of China. One phylogenetic analysis of whole-ge- man physiology that has a [1] helix-circle helix kind of construction now. However, there are presently fewer promising medications tivated by the low amount of oxygen in mammals. The synthesis nome sequences showed that bats are the main reservoir of COVID-19. The responsible intermediate host has not been found till are available on 2019-nCoV/SARS-CoV-2. There is a relationship [1]. A Heterodimer, crown-like structure present on the SARS-CoV virus, has 2 subparts HIF-1α and HIF-1β. HIF-1α is a protein ac- of HIF-1α protein is controlled with the help of amount of O2 in Citation: Tulsi Patil., et al. “Role of HIF 1 α in Covid-19 Disease". Acta Scientific Nutritional Health 5.6 (2021): 60-64. Role of HIF 1 α in Covid-19 Disease 61 cells and O2 homeostasis. HIF-1 α activation plays important role SARS-CoV and SARS-CoV-2 in the blood, and wound healing. Hypoxic condition activates the to another is high. Gene sequencing studies of identical two SARS in hypoxic conditions. Hypoxic conditions are generally caused It is detected that SARS-CoV-2 has less risk as compared to by, for example, high-temperature levels, a low number of RBCs SARS-CoV or influenza virus, but the rate of transmission from one body. Synthesized transcript genes encode numerous components [2]. The spike proteins of both viruses have nearly the same struc- carrier proteins (GLUT6, GLUT8, GLUT10, GLUT12, and GLUT13), ACE2 [5]. SARS-CoV-2 identifies the ACE2 of humans more strongly HIF-1α that prompts the synthesis of various genes in the human are Hematopoietic hormone, Enzymes (involve in glycolysis like hexokinase, phosphofructokinase, and pyruvate kinase), Glucose andVEGF. HIF-1 is significant in the early stages of development, endurance, cardiovascular capacities, Vascularization, and oncogenic tumors. viruses showed that both possess the nearly same gene sequencing tures and also having similarities in amino acid sequences about 76.5% [3,4]. SARS-CoV-2 has a high power of binding for human than SARS-CoV, which leads to rising the power of SARS-CoV-2 to transfer from one person to another (Figure 2). Hypoxia and HIF 1 α responses HIFs are present in all cells of the body, and partial pressure of oxygen plays an important role in the activation HIFs protein. The whole process depends upon the environment to which the cells are exposed. Following is the flowchart of the hypoxic condition and its corresponding HIF 1 α response (Figure 1). Figure 2: Interaction of SAR-COV and SAR-COV 2 with the ACE2 receptor. ACE2 and HIF-1α in coronavirus pathophysiology Relatively very little data available regarding the detailed tran- scription of ACE2. Although angiotensin proteins, some other peptides, and steroid hormones seem to modulate ACE2 protein level. Decreased amount of oxygen leads to a hypoxic condition called hypoxia, which increases the hypoxic HIF-1α protein level and si- multaneously decreases the level of ACE2 in the human body. Fur- ther experimentation has shown that hypoxic condition induced Figure 1: The flowchart of transcription genes and hypoxic responses regulated by HIF. (OXPHOS: Oxidative phosphorylation, INFOS: Inducible nitric oxide synthase, EPO: Erythropoietin, HO-1Heme oxygenase-1, VEGF: Vascular endothelial growth factor). HIF-1α protein enhances the ACE synthesis which, prompts an increased amount of Ang II (angiotensin) enzyme [4] and overall this process modulates the reduction in ACE2 with the help of the Ang II enzyme (Figure 3). The function of HIF 1 α in the ACE expression Hypoxia directs ACE and ACE2 articulation in extremely alter- native manners [6]. HIF-1 α up-managed ACE, yet it down-directed ACE2. Besides, excessive expression of HIF-1 α activates the move- Citation: Tulsi Patil., et al. “Role of HIF 1 α in Covid-19 Disease". Acta Scientific Nutritional Health 5.6 (2021): 60-64. Role of HIF 1 α in Covid-19 Disease 62 contrasted and controls during the hypoxic environment of cells [4]. This investigation exhibits that HIF-1 can up-direct ACE and down-manage ACE2. Role of HIF 1 α in influenza A virus It is found that the amount of HIF-1α contributes to the multi- Figure 3: HIF-1α increased concentration of Ang II (angioten- plication of the influenza A virus in the infected human cells. HIF- sin)and mediates a decrease in ACE2. 1α promotes autophagy in type II epithelial cells of alveoli. Various cytokines are released in the infectious condition of the virus such ment of the ACE Promoter, however not ACE2. One test performed on the Effects of hypoxia on angiotensin-changing over a catalyst (ACE) and ACE2 synthesis in hPASMCs cells showed that excessive as TNF-α and IL-6 and their expression regulation is also done with the help of HIF-1α. Nuclear accumulation of HIF-1α enhances the level of proinflammatory cytokine in influenza A virus-infected cells. The overall process shows that the HIF-1α synthesize and ac- tivates proinflammatory cytokine in influenza A virus infection [7]. expression of HIF-1 could up-manage ACE protein articulation, Natural HIF-1 alpha modulators dition, however not in HIF-1α treated cells. Conversely, the ACE2 the HIF-1α protein [8]. however down-direct ACE2, without hypoxia. Furthermore, no- ticed that the average up-regulation of ACE during the hypoxic conprotein level was particularly expanded in HIF-1α treated cells Inhibits the Fe(II)-dependent asparaginyl and prolyl hydroxylases. Desferri-exochelin DFE 722 SM Ciclopirox olamine and 8-methyl-pyridoxatin N-oxaloylglycine Alahopcin and dealanylalahopcin 3-carboxy-N-hydroxy pyrollidone and 3-carboxymethylene N-hydroxy succinimide Indirubin 5-iodoindirubin-3’-oxime and 5-methylindirubin-3’-oxime NO donor L-penicillamine, S-nitroso-N-acetyl-D, and S-nitrosoglutathione Vinblastine and Colchicine, and the synthetic MDA nocodazole Dibenzoylmethane,(Glycyrrhiza glabra) Quercetin Green tea catechins Dihydrotestosterone Several natural components exhibit the role in stabilization of [9] Inhibition of asparaginyl and prolyl hydroxylases. [10] Inhibition of collagen prolyl hydroxylase. [12] Inhibition of 2-oxoglutarate,prolyl-4-hydroxylase, and Fe(II) dependent oxygenases. HPH(Hif prolyl-hydroxylase) inhibitors. [11] [13] Inhibits GSK3β(glucogen synthase kinase 3β) and prevents a decrease in HIF-1α protein. [14] Increases the level of HIF-1α protein. [16] Increases HIF-1α protein accumulation and activate HIF-1 transcription from the VEGF promoter in A-172 human glioblastoma and Hep3B cells. Stabilize of the HIF-1α protein. Activates HIF-1α protein in normoxic conditions. At high concentrations (100 μM) Activates HIF-1. Increases the amount of HIF-1α protein and activates HIF-1. Table 1: Natural HIF-1α modulators. Citation: Tulsi Patil., et al. “Role of HIF 1 α in Covid-19 Disease". Acta Scientific Nutritional Health 5.6 (2021): 60-64. [15] [17] [18] [19,20] [17] Role of HIF 1 α in Covid-19 Disease Conclusion It is found that there is a relationship between HIF-1 and ACE2, therefore HIF-1 will help us to discover new treatment options for COVID-19 virus infection. HIF-1 α protein plays a crucial function in various processes of the mammalian body. 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