Immunotherapy of COVID-19 with poly (ADP-ribose) polymerase inhibitors:
starting with nicotinamide?
Background and purpose: COVID-19 induces a proinflammatory environment
that is stronger in cases requiring intensive care. Overexpression of
the aryl hydrocarbon receptor (AhR) by COVID-19 may activate nuclear
poly (ADP-ribose) polymerase 1 (PARP 1) thereby inducing cell death by
NAD+ and ATP depletion. The purpose of this review is to propose PARP 1
inhibition as a COVID-19 therapy, starting with nicotinamide.
Experimental approach: Evidence for the above effects of COVID-19, other
coronaviruses and lung conditions will be reviewed. Key results: A
proinflammatory environment characterises all the above conditions
irrespective of severity. The AhR is overexpressed by various
coronaviruses, the pneumovirus respiratory syncytial virus (RSV) and in
chronic obstructive pulmonary disease (COPD) patients. PARP 1 is
overexpressed in COPD and possibly also asthmatic patients. Conclusions:
It is almost certain that PARP 1 is overexpressed by COVID-19. A
sequence of events involving PARP 1 and culminating in patient mortality
is proposed. PARP 1 inhibition should be the focus of COVID-19 therapy.
Potent PARP 1 inhibitors are undergoing trials in cancer, but the highly
desirable biochemical and activity profiles of the NAD(P)+ precursor and
PARP 1 inhibitor nicotinamide justify its use, initially in conjunction
with standard clinical care or combined with other agents, and
subsequently as an adjunct to stronger PARP 1 inhibitors (once their
efficacy is proven) or other therapies. Implications: Preventing death
from COVID-19 infection with a widely available vitamin-like substance
with a unique biochemical and activity profile can present a great
clinical advance worldwide.