Amicoumacin-based prodrug development approach

• Published in: Bulletin of RSMU 2022-12 (2022(6)), p.82-88
• Main Authors: Shmygarev, VI, Prokopenko, YuA, Terekhov, SS, Zakharova, MYu, Dubinnyi, MA, Smirnov, IV, Yampolsky, IV, Tsarkova, AS
• Format: Article
• Language: English
• ISSN: 2500-1094; 2542-1204
• DOI: 10.24075/brsmu.2022.073

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.