The dihedral rotation of the 2-carboxamide group is necessary for successful PCET; then, the concerted PCET is the key process for the oxidative degradation of the pyrazine antiviral drugs by O2 •-. Therefore, if we can design a new pyrazine drug that inhibits the rotation of the dihedral angle around the 2-carboxamide group along the PCET, it may be possible to develop hypodegradable antiviral drugs resistant to O2 •-.