As it was confirmed in numerous researches, defeat of bodies and manifestation of a koronavirusny disease are connected with an expression of a receptor of SARS-CoV-2 and to - receptors on a membrane of target cells. S-protein which is responsible for a form of coronaviruses and is called still protein of an aculeiform shoot promotes fixing of receptors of a virus on a cell membrane. At the same time it is considered that receptors of an angiotensin-converting enzyme (APF-2) is the main receptors, the used coronavirus for penetration into a cell. At the same time, there are data on SARS-CoV-1 which show that at APF-2 inactivation penetration of a virus into lungs of the mice infected with a virus considerably decreases.
Proceeding from it, a number of authors defined pharmacological strategy for decrease in APF-2 levels to study potential therapeutic influence for slowing down of penetration of a virus and, therefore, decrease in a possibility of the multiorgan complications caused by SARS-CoV-2 infection. To define the expected drugs capable to change the level of protein APF-2 methods of generation of cells of heart from human embryonic stem cells (hESC) in big scales were used and screening with components of medicines was made.
It was revealed that drugs which are most effective for decrease in APF-2 levels are united that they slow down the system of signals of the androgenic receptor (AR). These drugs were effective in decrease in APF-2 and level of the serinovy TMPRSS2 proteinase (which is also taking part in penetration of SARS-CoV-2 into a cell) in cellular membranes and also reduced introduction of the receptor-binding domain of an aculeiform shoot.
The analysis showed the high level of an expression of receptors SARS-CoV-2, APF-2 and to - receptors, TMPRSS2 and FURIN in adult cells of tissues of heart, gullet, lungs and a large intestine. Assuming communication of serious consequences of COVID-19 at patients with cardiovascular complications and a significant role of APF-2 in heart physiology, authors of a research were focused on regulation of APF-2 level in heart cells. Because of the restrictions connected with allocation and maintenance of cells of the person from initial fabrics they used earlier defined method of differentiation of hESC as alternative strategy for generation of cells of heart. Earlier published these transkriptomik of the cells made this way from hESC confirmed an expression of receptors of SARS-CoV-2 and to - receptors in cardiomyocytes and other cells. The differentiated cells also positively were painted at reaction to APF-2 with use of a method of an immunofluorescence. Investigating modulators of APF-2 levels in the cells of heart received from hESC, authors carried out screening of the library of small molecules of Selekham made of 1443 drugs approved FDA (Food and Drug Administration). APF-2 levels were measured in the cells which were affected by medicine with use of screening and thus the list of drugs which considerably slow down was defined or raise APF-2 expression.
Further authors investigated whether there is a potential general way for decrease in APF-2 levels on a membrane of cells of heart when using kandidatny drugs. They used the computing SEA tool for forecasting of interactions of protein and medicine. The offered SEA of couple "medicine — protein" were filtered based on the ratio of human proteins and the predicted interaction of R-values <0.05.
Considering convincing clinical data on disproportionately great influence of COVID-19 on men which consists in heavier current at them this pathology, precisely established peptidase role in modulation of APF-2 and to - SARS-Co-V-2 receptors, possible communication between an expression of APF-2 and sex hormones, authors of a research sought to open specific medicinal and proteinaceous interactions, to establish influence of androgens on weight of a koronavirusny infection and also to find out possible ways of weakening of this influence.
As a result results of a research showed that inhibitors 5 - alpha reductases which weaken signaling of androgens can reduce APF-2 levels and, thus, reduce introduction of the virus receptor-binding domain of an aculeiform shoot. These drugs which are usually appointed for treatment of diseases of a prostate block transformation of testosterone into its active form dihydrotestosterone (DGT, 5α-дигидротестостерон, 5α-ДГТ, androstanolon or stanolon). It is considered that the specified drugs thereby show the multi-purpose potential for treatment of COVID-19 and further researches in this direction are required.