Removing Fuel from Coronavirus Fire: Blocking Superoxide through NOX Inhibition

Abstract

Background: The toll of the coronavirus pandemic needs little introduction. The commencement of vaccination is both impressive and welcome but insufficient to achieve herd immunity. Consequently, additional approaches are urgently needed for pandemic abatement. \n \nHypothesis: Inhibiting the human NADPH oxidase enzyme can reduce the morbidly and mortality of severe coronavirus infection by preventing excess production of superoxide free radicals, the reason behind severe infection. This can be accomplished with apocynin, a historic natural well-researched compound, and its derivative paeonol, present in the readily available peony root. \n \nEvidence: The common denominator of who dies from coronavirus (the aged, males, post-menopausal females, African Americans, obesity, diabetics, hypertensives, chronic heart, liver, kidney disease patients) is oxidative stress. Moreover, the source can be traced specifically to a higher endogenous production of the reactive oxygen species superoxide from NADPH-oxidase activity shared by these groups. In addition, interventions for coronavirus infection that act on the host (Vitamins C, D, B3, melatonin, estrogen, nicotine) all decrease NADPH oxidase activity even when not the stated reason for use. Finally, apocynin’s well-studied use as a highly effective NADPH inhibitor is covered. \n \nImplications: The direct implication is reduction in serious infections and deaths. especially in COVID-vulnerable groups. Apocynin may also be capable of targeting other lethal viruses that co-evolved with bats in the same oxygen-rich milieu, such as Ebola. An intriguing potential application is in Chronic Fatigue Syndrome, Mast Cell Activation Syndrome, and dysautonomia, all with symptoms resembling the COVID long-hauler syndrome. Finally, as the role of NADPH oxidase in conditions of aging such as cardiovascular disease and neurodegeneration is being increasingly recognized, apocynin as “vitamin of the 21st century” for longevity warrants investigation. \n \nConclusion: Oxidative bursts kill pathogens but can be exploited by viruses to replicate. By removing this fuel from coronavirus fire, apocynin and peony root are safe available compounds dating to antiquity that become attractive contenders for rapid pandemic relief.