The SARS-CoV-2 virus infects cells of the person by linking of the S-protein with a receptor: angiotensin - the converting enzyme 2 (ACE2), the ektomembranny integrated glycoprotein, weighing 120 kd, expressed on a surface of cells in lungs, heart, kidneys and intestines. Linking of a SARS coronavirus with ACE2 is followed by merge of virus and plasmatic membranes, endocytosis and an infection of a cell. ACE2 expression on cells of a respiratory epithelium is important for development of pathology at COVID-19. The infection usually begins in an epithelium of the upper airways and extends then to alveoluses in lungs, at the same time pathological processes are more expressed at patients with the weakened immune response and reduced ability to counteract spread of an infection. COVID-19 usually causes easy symptoms (in 80% of patients), but the hard cases of a disease demanding hospitalization of an intensive care meet at a number of patients and in some situations such cases conduct by death. The increased predisposition to complications and mortality meets at patients with associated diseases, especially at patients of old age or having a hypertension, cardiovascular diseases, diabetes, chronic diseases of lungs and with the weakened immunity.
The SARS-CoV-2 virus in many characteristics is similar to the SARS-CoV-1 virus which caused a pandemic in 2002-2003. Its main features include about 80 percentage identity of a genome, a range of the struck fabrics, mortality owing to ORDS and a cellular receptor: ACE2. In comparison with SARS-CoV-1, the SARS-CoV-2 virus has bigger, approximately by 4 times, affinity to ACE2. Because of their similarity information on SARS-CoV-1 can help with development of hypotheses of treatment of the infection caused by SARS-CoV-2 including selection of the pharmacological means effective for clinical use.
Level of an expression of ACE2 is high in a parenchyma of lungs, especially in pnevmotsita of the II type (alveolar II cells). Pnevmotsita II of type produce pulmonary surfactant, phospholipids which reduce surface intention that is necessary for maintenance of alveolar structure. Pnevmotsita II of type can be also differentiated, turning into the alveolar cells of the I type forming structure of alveoluses that is the mechanism of replacement of the struck cells of pnevmotsit І type. The SARS-CoV-2 and SARS-CoV-1 viruses break structure of alveoluses that is the leader pathological process in lungs which is characterized by the increased liquid penetration, death of cells and inflammation and also decrease in gas exchange and level of surfactant. The SARS-CoV-2 virus infects pnevmotsita, contacting ACE2 that leads to decrease in conversion of angiotensin 2 (ANG II) in derivative peptides, for example, to decrease in angiotensin (ANG (1-7)) and its effects opposite to that ANG II. Therefore, the ANG II levels increase in an alveolar microenvironment that can potentially influence cells of different types.
ANG II has pro-apoptotic effect on pulmonary epithelial cells and this reaction will be coordinated with the pathology caused by the SARS viruses, i.e. considerable defeat of an epithelium and alveoluses and also death of cells. Besides, ANG II promotes, and ANG (1-7) suppresses the epithelial and mesenchymal transformation (EMT) therefore epithelial cells get more fibrous phenotype. ANG II also reduces clearance of alveolar liquid. Apoptosis and EMT of epithelial cells of alveoluses are followed by increase in secretion of pro-inflammatory cytokines (for example, IL1-β, IL-6, MCP-1, TNF-α, etc.). Epithelial cells interact with immune cells, in particular, during infection and apoptosis. These effects are aggravated with secretion of components system renin-angiotensin-aldosteronovoy the activated miofibroblasta and epithelial cells undergoing apoptosis that enhances effects of ANG II in a contour of positive feedback.
ANG II also has pro-fibrous effect on fibroblasts of intersticial spaces around alveoluses and increases apoptosis of endothelial cells and permeability of an endothelium in a surrounding capillary network that can increase intake of liquid and immune infiltration in affected areas of lungs. ANG II also influences various types of immune cells, strengthening infiltration of macrophages, producing the active forms of oxygen (AFO) and release of pro-inflammatory cytokines. In addition to immune cells, ANG II can stimulate, and ACE2/ANG to inhibit pathological products of AFK pulmonary fibroblasts. Production of AFK the activated fibroblasts is key factor of defeat of an epithelium in models of pulmonary fibrosis.
Thus, these data allow to assume that the imbalance in operation of the peptides which are formed as a result of action of ACE1 and ACE2 strengthens action of Angiotenzina-II (ANG II) and is the major driving factor of a pathogeny of COVID-19.