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Information × Registration Number 0222U000438, 0121U111840 , R & D reports Title The chemical genetics approach to study the ACE-2 knockdown consequence as the pharmacological model of COVID19 side-effects in nervous, gut, hemostatic and cardiovascular systems popup.stage_title Head Borysova Tatiana О., д.б.н. Registration Date 09-01-2022 Organization Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine popup.description2  Validation of newly synthesized ACE2 inhibitors using platelets, leukocytes and brain nerve terminals, diversification of their specific and nonspecific effects, study of neurotoxicity and changes in platelet function caused by suppression of ACE2 levels by developed chemicals. It was shown for the first time the absence of nonspecific membranetropic effects of newly synthesized stereoisomer inhibitors ACE2, EBC-36032 and EBC-36033. Both inhibitors did not cause proton gradient dissipation of platelet secretory granules, did not affect platelet aggregation and activation. EBC-36032 and EBC-36033 did not cause changes in the transport of L-[14C]glutamate in isolated segments of the gut (inverted intestinal sac). Both inhibitors did not affect the integrity of the membrane and its permeability to neurotransmitters, did not cause the development of acute neurotoxicity. Unchanged extracellular levels of L-[14C]glutamate and [3H]GABA in the presence of inhibitors indicated absence of their effect on the appropriate tonic balance of excitation and inhibition signals, which ensures their safety, the feasibility of their further testing and prospects for use in medicine. Both inhibitors at a concentration of 100 μM reduced the initial rate of transporter-mediated accumulation of L-[14C]glutamate by nerve terminals. Dysfunction of ACE2 in neurons during infection by SARS-COV may be accompanied by decreased uptake of glutamate and GABA, as well as exocytosis of GABA, which can be the basis of acute and long-term neurological complications of COVID 19. From the point of view of antiviral therapy targeting ACE2, new ACE2 inhibitors should be tested for possible neurological side effects. Product Description popup.authors Krysanova Nataliya V Pastukhov Artem O. Pozdnyakova Natalia Heorgiivna popup.nrat_date 2022-03-09 Close