AMICOUMACIN-BASED PRODRUG DEVELOPMENT APPROACH
Bulletin of Russian State Medical University
; 2022(6):99-105, 2022.
Article
in English
| EMBASE | ID: covidwho-2245181
ABSTRACT
Coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, is highly contagious and has a severe morbidity. Providing care to patients with COVID-19 requires the development of new types of antiviral drugs. The aim of this work is to develop a prodrug for the treatment of coronavirus disease using the antibiotic Amicoumacin A (Ami), the mechanism of action of which is based on translation inhibition. Enzymatic hydrolysis of an inactivated prodrug by the SARS-CoV-2 main protease can lead to the release of the active Ami molecule and, as a consequence, the suppression of protein biosynthesis in infected cells. To test the proposed hypothesis, a five-stage synthesis of an inactivated analogue of Amicoumacin A was carried out. Its in vitro testing with the SARS-CoV-2 recombinant protease MPro showed a low percentage of hydrolysis. Further optimization of the peptide fragment of the inactivated analog recognized by the SARS-CoV-2 MPro protease may lead to an increase in proteolysis and the release of Amicoumacin A.
article; controlled study; enzymatic hydrolysis; enzyme activity; human; in vitro study; nonhuman; protein degradation; protein synthesis; Severe acute respiratory syndrome coronavirus 2; synthesis; antibiotic agent; antivirus agent; coronavirus 3C protease; endogenous compound; peptide fragment; prodrug; proteinase; unclassified drug
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Bulletin of Russian State Medical University
Year:
2022
Document Type:
Article
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