Hydrophobic Catalysis by L-Ascorbic Acid: A supramolecular Strategy to counter the SARS-CoV2 ADP Ribose Glycohydrolase
Abstract and Oral Presentation at the Southwest Regional Meeting of the American Chemical Society Austin, Texas on November 1, 2021 contributed by Robert Michael Davidson and Timothy Richard Winey
A supramolecular strategy is presented for tackling the ongoing, scourge of SARS-CoV2 pandemic. The strategy depends critically on (a) recently introduced non-enzymatic group transfer catalysis, ascorbolysis, and universal nonspecific mesenchymal reaction theoretical framework, and (b) recently introduced hydrophobic catalysis theory of polynucleotide folding. Relative hydrophobicity of microenvironment may phase-coherently drive protein folding, nucleic acid folding, and induce intramolecularity of hydrogen bonding and intramolecular-1,4-hydrogen atom transfer during ascorbolysis. Ascorbolysis, a redox active, hyperconjugated vinylogous variant of acidolysis, has been proposed to be a broadly generalizable subsystem of non-enzymatic group transfer catalysis. The unfolded RNA response of the SARS-CoV2 genome may present a window of vulnerability in which the viral pathogen is susceptible to SN2 nucleophilic attack by the L-ascorbic acid free radical in the presence of Cu2+ and sunlight in a moderately acidic, mildly oxidative, relatively hydrophobic microenvironment. The net result might well include regiospecific cleavage of SARS-CoV2 RNA and/or its protein macrodomain at sites with hydrophobic sequence-based topological motifs described for the SARS-CoV2 genome and macrodomain which is now known to counter human innate immunity by hydrolyzing ADP-ribosylated proteins. Anomeric fidelity of non-enzymatic transglycosylation reactions during inflammatory states is proposed to arise from ascorbolysis and chirality-induced spin-selectivity of ortho/para nuclear spin states of water.
Winey, T.R. & Davidson, R.M. Hydrophobic Catalysis by L-Ascorbic Acid: A supramolecular Strategy to counter the SARS-CoV-2 ADP Ribose Glycohydrolase. figshare. Presentation. (2021) https://doi.org/10.6084/m9.figshare.17207309.v1