PRECISION NUTRITION
TO RESET
Viral Hijacked Host Factors
Precision Nutrition to Reset Viral Hijacked Host Factors
Reset of Virus-Hijacked ACE2/RAAS
ACE2 is a key component of the renin-angiotensin-aldosterone system (RAAS) that plays a vital role in regulating blood pressure, vaso-constriction, sodium retention, tissue remodeling, pro-inflammatory and pro-fibrotic functions. The viral hijacking of human ACE2 receptor disrupts RAAS activation, upregulates NF-κB pathway, triggers cytokine storm, hypertension, cell proliferation, inflammation, and fibrosis, where all elicit detrimental effects on every bodily organ during viral-induced HMR/D. SARS-CoV-2 infection requires a high basal energy expenditure for immune activation, hyper-inflammation (‘cytokine storm’), anorexia followed by muscle loss, weakness, and fatigue. Circulating autoantibodies may also have a major role in the manifestation of long-term fatigue in viral-induced HMR/D.
L-Carnitine: L-Carnitine, a micronutrient composed of essential amino acids (i.e., lysine and methionine), is a cofactor that converts long-chain free fatty acids to acyl-carnitine and transfers these metabolites into the mitochondrial matrix. This hydrophilic AA is widely distributed in central and as well as peripheral nervous system, heart and skeletal muscle, holding >95% of body's total carnitine. L-Carnitine plays a vital role in lipid metabolism and its deficiency could induce feeling of tiredness or general fatigue. Therefore, acetyl-L-carnitine supplementation could generate energy from mitochondrial oxidation of fatty acids and help mitigate fatigue in HMR/D patients.
Reset of Virus-Hijacked NRP1
Neuropilin (NRP)-1 is expressed in olfactory epithelium, astrocytes, and neuronal cells (lack of ACE2 expression) and serve as major CSR for SARS‐CoV‐2 infection of the central nervous system (CNS). Viral hijack of NRP1 facilitates CNS invasion of SARS-CoV-2 through the blood brain barrier (BBB), and consequential neuro-cognitive symptoms such as anosmia, ageusia, headaches, confusion, delirium, and strokes in early COVID-19. The ensuing pathophysiology involves viral-induced neuronal damage, neuroinflammation, BBB rupture, microvasculitis and hypoxia. Neuroinflammation with hypometabolic lesions cause chronic cognitive impairment in COVID patients. Neurological symptoms in viral-induced HMR/D include damage to CNS and PNS, encephalitis, myelitis, myositis, Guillain Barré syndromes, and cognitive impairments. These neuro-complications are prevalent among one third of COVID-19 cases, and this clinical condition may persist as chronic symptoms in PASC patients as frequent complaints of brain fog (81%) and fatigue (58%). Nutritional reset of neuro cognitive dysfunction from viral hijack of NRP1 indeed is of high priority in clinical management of viral-induced HMR/D.
Melatonin: Melatonin (N-acetyl-5-methoxytryptamine) is a derivative of tryptophan, synthesized/secreted by the pineal gland and reaches peak levels in plasma during the night hours. This chrono-biotic hormone serves as a photo-periodic switch, influencing the activity of supra-chiasmatic nucleus and facilitates human sleep-wake. Melatonin plays a multi-functional role including the regulation of circadian rhythms, immune modulation, oxidative processes, apoptosis, and mitochondrial homeostasis. Melatonin deficiency may lead to cardiovascular disease with manifestations of hypertension and myocardial ischemia/reperfusion injury, which are prevalent in COVID-19; as well as neuro-cognitive complications such as brain fog, sleep disorders and ME/CFS, which are persistent among PASC. Melatonin with its antioxidant, anti-inflammatory, immune-modulatory, and anti-apoptotic effects, is considered a potential therapeutic reset for viral-induced HMR/D. Based on several human RCTs, melatonin is considered an effective intervention to resolve delirium, ameliorate respiratory stress (i.e., ARDS), and restore circadian balance in viral-induced HMR/D.
Reset of Virus-Hijacked Serine Proteases
In healthy lungs, type II transmembrane serine proteases (i.e., TTSPs: TMPRSS2, CTSL, HAT) play a major role in cellular regeneration, repair, and homeostasis. Furthermore, anti-proteases (i.e., secretory leukocyte protease inhibitor, SLPI), are important for proteolytic inhibition and host defense. A functional balance between proteases and anti-proteases is vital to ensure respiratory homeostasis. Any imbalance towards increased protease expression and activity may lead to overt inflammation and trigger chronic lung disorders such as emphysema and COPD. Furthermore, respiratory serine proteases that belong to the TTSP family, increase host susceptibility to SARS-CoV-2 infection. Anti-proteases, such as SLPI, inhibit the activity of serine proteases and block viral entry into host target cells. Therefore, the protease and anti-protease balance not only is critical for respiratory homeostasis but also serves as a powerful determinant of SARS-CoV-2 pathogenesis. Nutritional antioxidants could stimulate anti-protease secretion, decrease protease activity and protect epithelial cells against viral infection. Thus, antioxidants serve as regulators of the protease/antiprotease balance that could effectively combat viral-induced HMR/D.
Nrf2, the innate transcription factor, regulates synthesis and activity of several antioxidant enzymes to resolve OxS, and prevent tissue damage in lungs. Nrf2 also regulates TMPRSS2, protease/ antiprotease balance and protects the respiratory milieu against viral infections. Thus, bioactive nutrients that activate Nrf2 could reduce persistent OxS as well as help in functional optimization of viral-hijacked serine proteases and reset HMR/D.