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April 22nd, 2020
April 22nd, 2020
BST* Executive summary prepared by Marina T. Botana1 and Raymond C. Valentine2
1 São Paulo, SP, 04116-240, Brazil; m.botana23@gmail.com ; +55-11-97283-7799
2 Professor Emeritus, University of California, Davis, CA 95616, USA; ray@ecowizards.com ; +1-802-275-2980
COVID-19 virus likely infects the brain causing irreversible damage. We suggest that it might be a consequence of energy stress, which is well known to be the trigger of death cascades. This view opens new treatment strategies for compromised patients. Once again, the devil is in the details.
Figure 1: Several human lipid viruses, including the novel coronavirus fatally infecting the brain a) Brain tomography of a newborn baby with microcephaly and congenital Zika syndrome adapted from Hazin et al., 20161; b) Tomography of different brain sections showing diffusive edema with multiple high density lesions (in white arrows) adapted from Xu et al., 20052; c) Tissue distribution of ACE2 receptor in humans, including the brain, which are possible targets of COVID-19 (Baig et al., 20203).
1) Past and new evidences of infection by lipid viruses show great incidence of brain infection and damage1,2,3, 4, 5 (Figure 1). However, there is still a lack of information about HOW brain infection takes place after contamination.
2) Lipid viruses hijack the lipidome of the host 6,7,8,9 for the purpose of virus gain. The resulting cocktail of fatty acids and detergent like derivatives (i.e. lysolipids) (Figure 2) are highly toxic to host cells organs and tissues.
Figure 2: a) Higher concentrations of lysolipids and free fatty acids in serum from COVID-19 patients (adapted from Yan et al., 20199); b) Schematic representation of the changes in molecular dimensions imposed in pure DOPE (dioleoylphosphatidylethanolamine), a structural phospholipid, when doped with lysolipids10; c) Changes in membrane curvature promoted by lysolipids and free fatty acids (adapted from Arouri et al., 201311).
3) We propose that the accumulation of these groups of membrane uncoupling byproducts in the blood serum of infected patients can target mitochondria and uncouple energy synthesis12,13.
4) Protecting both the brain and the lungs of COVID-19 patients might save their lives in both the short and long term by preventing brain damage.
Full report explaining how lipid viruses infect the brain and induce death cascades will follow.
References:
1- HAZIN, Adriano N. et al. Computed tomographic findings in microcephaly associated with Zika virus. New England Journal of Medicine, v. 374, n. 22, p. 2193-2195, 2016.
2- XU, Jun et al. Detection of severe acute respiratory syndrome coronavirus in the brain: potential role of the chemokine mig in pathogenesis. Clinical infectious diseases, v. 41, n. 8, p. 1089-1096, 2005.
3- BAIG, Abdul Mannan et al. Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host–virus interaction, and proposed neurotropic mechanisms. ACS chemical neuroscience, 2020.
4- LI, Yan‐Chao; BAI, Wan‐Zhu; HASHIKAWA, Tsutomu. The neuroinvasive potential of SARS‐CoV2 may be at least partially responsible for the respiratory failure of COVID‐19 patients. Journal of medical virology, 2020.
5 - NETLAND, Jason et al. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. Journal of virology, v. 82, n. 15, p. 7264-7275, 2008.
6 - LEIER, Hans C.; MESSER, William B.; TAFESSE, Fikadu G. Lipids and pathogenic flaviviruses: An intimate union. PLoS pathogens, v. 14, n. 5, 2018.
7 - SYED, Gulam H.; AMAKO, Yutaka; SIDDIQUI, Aleem. Hepatitis C virus hijacks host lipid metabolism. Trends in Endocrinology & Metabolism, v. 21, n. 1, p. 33-40, 2010.
8 - SHEN, Bo et al. Proteomic and Metabolomic Characterization of COVID-19 Patient Sera. medRxiv, 2020.
9 - YAN, Bingpeng et al. Characterization of the lipidomic profile of human coronavirus-infected cells: Implications for lipid metabolism remodeling upon coronavirus replication. Viruses, v. 11, n. 1, p. 73, 2019.
10- FULLER, N.; RAND, R. P. The influence of lysolipids on the spontaneous curvature and bending elasticity of phospholipid membranes. Biophysical journal, v. 81, n. 1, p. 243-254, 2001.
11- AROURI, Ahmad; MOURITSEN, Ole G. Membrane-perturbing effect of fatty acids and lysolipids. Progress in lipid research, v. 52, n. 1, p. 130-140, 2013.
12 - CRAKES, Katti R. et al. PPARα-targeted mitochondrial bioenergetics mediate repair of intestinal barriers at the host–microbe intersection during SIV infection. Proceedings of the National Academy of Sciences, v. 116, n. 49, p. 24819-24829, 2019.
13 - DEMINE, Stéphane; RENARD, Patricia; ARNOULD, Thierry. Mitochondrial uncoupling: a key controller of biological processes in physiology and diseases. Cells, v. 8, n. 8, p. 795, 2019.
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