Electrochemical and Mechanistic Study of Oxidative Degradation of Favipiravir by Electro-generated Superoxide through Proton-coupled Electron Transfer

Abstract

Electrochemical analyses aided by density functional theory calculations were used to investigate the oxidative degradation of pyrazine antiviral drugs, 3-hydroxypyrazine-2-carboxamide (T-1105) and 6-fluoro-3-hydroxypyrazine-2-carboxamide (favipiravir, T-705), by electro-generated superoxide radical anion (O2 •− ). T-1105 and T-705 are antiviral RNA nucleobase analogs that selectively inhibit the RNA-dependent RNA polymerase. They are expected as a drug candidate against various viral infections, including COVID-19. The pyrazine moiety was decomposed by O2 •− through proton-coupled electron transfer (PCET). Our results show that its active form, 2 pyrazine-ribofuranosyl-5'-triphosphate, is easily oxidized under inflamed organs by overproduced O2 •− through the PCET mechanism in the immune system. This mechanistic study implies that the oxidative degradation of pyrazine derivatives will be prevented by controlling the PCET through simple modification of the pyrazine structure.

Conventional and synchronous spectrofluorometric determination of the recently administered drugs for treatment of COVID-19 favipiravir and apixaban

“…1 The literature was screened for analytical procedures that were applied for determination of FAV and APX. For FAV, a spectrophotometric method 7 , two conventional spectrofluorometric methods 8,9 , electrochemical methods [10][11][12] , and HPLC methods 7,9,13 were reported. On the other hand, spectrophotometric [14][15][16][17] , spectrofluorometric 18 , electrochemical 19 , and HPLC [20][21][22][23][24] methods were reported for the assay of APX.…”