Coronavirus Infection and PARP Expression Dysregulate the NAD Metabolome: A Potentially Actionable Component of Innate Immunity

Collin D. Heer; Daniel J. Sanderson; Yousef M.O. Alhammad; Mark S. Schmidt; Samuel A.J. Trammell; Stanley Perlman; Michael S. Cohen; Anthony R. Fehr; Charles Brenner

MHV infection in murine BMDMs launches a transcriptional program that induces transcription of PARP isozymes 7, 9, 10, 11, 12, 13 and 14 by greater than 5-fold (Grunewald et al., 2019; Grunewald et al., 2020) . We utilized RNAseq data from SARS-CoV-2 infection of a human lung carcinoma cell line, A549, and normal human bronchial epithelia cells, NHBE (Blanco-Melo et al., 2020) . To determine whether SARS-CoV-2 dysregulates the NAD system upon infection we assembled and analyzed a set of 71 genes that encodes the enzymes responsible for conversion of tryptophan, NA, NAM, and NR to NAD + , plus the enzymes responsible for NAD(H) phosphorylation, NADP(H) dephosphorylation, NAD + -dependent deacylation, ADP-ribosylation, cADP-ribose formation, nicotinamide methylation/oxidation, and other related functions in transport, binding, redox and regulation (Supplementary Information 1). As shown in Figure 1A , SARS-CoV-2 induces transcription of PARPs 9, 10, 12 and 14 with lesser effects on PARP7 and PARP13 in A549 cells and induces transcription of PARP9, 12 and 14 in NHBE cells.