ACE : angiotensin converting enzyme, ACE 2: angiotensin converting enzyme 2, Ang 1-7: angiotensin 1-7, Ang II: angiotensin 2, AT1R: angiotensin II type 1 receptor, NO: nitric oxide, ARDS: acute respiratory distress syndrome, SARS-CoV-2: severe acute respiratory distress coronavirus 2, TMPRSS2: transmembrane protease serine 2, ADAM17: ADAM metallopeptidase domain name 17, NOX: nicotinamide adenine dinucleotide phosphate oxidase, ROS: reactive oxygen species, VWF: von Willebrand factor, NETs: neutrophil extracellular traps. Author Contributions S-AM, AU, JK, DS, AH, and AA contributed to the writing of the original draft. is an essential protease required by SARS-CoV-2 to facilitate its access (Amraei and Rahimi, 2020). Recently, TMPRSS2 and ACE2 co-expression was reported among a subset of type II pneumocytes, which explains why SARS-CoV-2 contamination highly affects the lung function (Ziegler et al., 2020). During the biosynthesis phase, the SARS-CoV-2 structure and genome are synthesized using the host cellular organelles machinery. Subsequently, during the maturation phase, the viral structures are put together into new SARS-CoV-2 in the cells exponentially. Finally, the newly synthesized SARS-CoV-2 are released into the blood circulation by exocytosis, and the cycle will be repeated (Yuki et al., 2020). Open in a separate window Physique 2 The lifecycle of SARS-CoV-2 starting Methylphenidate from the penetration of the computer virus into the cell until its release. The computer virus requires both ACE2 and TMPRSS2 to facilitate its access. ACE: angiotensin transforming enzyme, TMPRSS2: transmembrane protease serine 2. Following viral endocytosis, ADAM metallopeptidase domain name 17 (ADAM17) activity increases which results in the shedding of the ectodomain of ACE2 from your cell surface (Hoffmann et al., 2020). ACE2 removal following SARS-CoV-2 contamination may lead to a physiological imbalance between ACE and ACE2 activity that favors ACE, hence leading to worsening of the disease. ACE2 shedding and internalization results in increased Ang II activity, as less ACE2 are available to cleave Ang II into Ang 1-7. Ultimately, this prospects to a shift from your ACE2/Ang 1-7/Mas axis to the ACE/Ang II/AT1R axis (Amraei and Rahimi, 2020). Pulmonary vasoconstriction and Methylphenidate raised blood pressure lead to pulmonary edema and eventually the endpoint complication; acute respiratory distress syndrome (ARDS), and death (Kuba et al., 2005; Klh?fek, 2020). In ARDS, it has been exhibited that pulmonary expression of ACE2 was decreased whereas ACE was elevated (W?sten-van Asperen et al., 2013). This prospects to a shift from your ACE2/Ang 1-7/Mas axis to the ACE/Ang II/AT1R axis with cardiovascular effects. Therefore, it is hypothesized that this administration of Ang 1-7 to the infected organism may protect from the severe end result of SARS-CoV-2 contamination, especially in hypertensive patients (Magalhaes et al., 2020). Recently, a few clinical trials related to the administration of Ang 1-7 to COVID-19 patients are registered at www.clinicaltrials.gov (“type”:”clinical-trial”,”attrs”:”text”:”NCT04332666″,”term_id”:”NCT04332666″NCT04332666, “type”:”clinical-trial”,”attrs”:”text”:”NCT04375124″,”term_id”:”NCT04375124″NCT04375124, “type”:”clinical-trial”,”attrs”:”text”:”NCT04570501″,”term_id”:”NCT04570501″NCT04570501, “type”:”clinical-trial”,”attrs”:”text”:”NCT04605887″,”term_id”:”NCT04605887″NCT04605887, and “type”:”clinical-trial”,”attrs”:”text”:”NCT04633772″,”term_id”:”NCT04633772″NCT04633772) to further investigate this hypothesis. Even though ACE2 has been recognized Methylphenidate as the receptor for SARS-CoV-2, there might be other receptors or co-receptors for this computer virus that are yet to be discovered. For instance, ACE2 knockout mice experienced a reduced incidence of SARS-CoV Methylphenidate contamination but the absence of ACE2 did not completely prevent the contamination from occurring (Kuba et al., 2005). This suggested that there could be other receptors involved in a viral invasion. Intracellular pathogens usually attach to more than one host cell surface structure that functions as the viral receptor. Carbohydrates, proteins, integrins, and membrane-bound ACE2 are common receptors used by viruses (Maginnis, 2018). Recently, Rabbit Polyclonal to FOXO1/3/4-pan CD147, a transmembrane glycoprotein that belongs to the immunoglobulin superfamily, was identified as a novel Methylphenidate receptor for SARS-CoV-2 (Wang et al., 2020b). CD147 is usually abundantly expressed in the epithelium and immune cells and plays a role in inflammatory processes and computer virus host cell access (Radzikowska et al., 2020). Coincidentally, CD147 was involved in SARS-CoV contamination, and CD147 antagonistic peptides have an inhibitory effect on SARS-CoV (Chen et al., 2005). Another possible receptor is CD209L (L-SIGN), which is a type II transmembrane glycoprotein identified as the receptor of SARS-CoV (Jeffers et al., 2004). Considering that SARS-CoV-2 has a similarity to SARS-CoV, CD209L is usually another potential receptor for SARS-CoV-2. In short, besides ACE2, there are several other potential receptors for SARS-CoV-2. Hypertension as a Risk Factor for Severe COVID-19 End result Hypertension has gained popularity among experts owing to its over-representation among COVID-19 patients (Schiffrin et al., 2020). The observational and retrospective studies conducted near Wuhan area have reported that hypertension is the most common co-morbidity observed in patients affected by COVID-19, ranging from 15 to 30% (Wang et al., 2020a; Zhang et al., 2020c; Zhou et al., 2020). In one of the largest studies conducted between December 11, 2019 and January 29, 2020 in Wuhan with data encompassing on 1,099 COVID-19 patients, 165 patients (15%) experienced high blood pressure. The same study also reported a total of 23.7% of hypertensive patients experienced higher disease severity compared to 13.4% of normotensive subjects. Whereas, 35.8% of.
