A Mechanistic Insight into Oxidative Degradation of Favipiravir by Electrogenerated Superoxide through Proton-Coupled Electron Transfer | Chapter 02 | Research Trends and Challenges in Physical Science Vol. 7

 This study provides a mechanistic understanding of the oxidative degradation of favipiravir by electrogenerated superoxide via proton-coupled electron transfer. The oxidative degradation of pyrazine antiviral drugs, 3-hydroxypyrazine-2-carboxamide (T-1105) and 6-fluoro-3-hydroxypyrazine-2-carboxamide (favipiravir, T-705), by the electrogenerated superoxide radical anion was investigated using electrochemical analyses aided by density functional theory calculations (O2-). T-1105 and T-705 are antiviral RNA nucleobase analogues that inhibit the RNA-dependent RNA polymerase selectively. They are likely to be used as a therapeutic candidate to treat a variety of viral diseases, including COVID-19. O2- degraded the pyrazine moiety via proton-coupled electron transfer (PCET). Our findings reveal that its active form, pyrazine-ribofuranosyl-5'-triphosphate, is easily oxidised by overproduced O2- in inflamed tissues via the PCET pathway in the immune system. This mechanistic work suggests that regulating the PCET via simple pyrazine structural alteration will prevent oxidative degradation of pyrazine derivatives.

Author(S) Details

Tatsushi Nakayama
Department of Pharmacy, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu 501-1196, Japan.

Ryo Honda
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.

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