Posted by A recent review of Italian researchers emphasized the role of membrane lipids in the infectivity mechanism of SARS-COV-2 (Covid-19) based on past studies on the attachment of viruses to host cells [1]. Lipid rafts, the cholesterol-rich parts of cell membranes serve as docking places of host cells for the viruses. SARS-COV-2 is a member of a virus family with a lipid envelope that fuses with the host cell through endocytosis, internalizing its components in the cell [2]. Glycoproteins S (spike proteins) of the new coronavirus (SARS-CoV-2) bind to the Angiotensin-Converting Enzyme 2 (ACE2) receptors on human respiratory epithelial cells. In vitro cell models expressing the ACE2 membrane protein have shown that depletion of cholesterol by MeβCD halved the number of bonds with viral S glycoproteins [3]. The molecule not only affects cholesterol levels [4-8] but also expression of the ACE2 receptor. Some studies showed that MeβCD treatment slightly and dose-dependently reduced expression of ACE2 in the cell membrane, also reducing the infectivity of coronaviruses, such as SARS-CoV [9].
Plant sterols, such as β-sitosterol, reduce the probability of HIV and HBV infectivity [10].
Cyclodextrins disturb the host cell membrane lipid composition this way reducing the attachment of the virus to the protein receptors, while phytosterols are cholesterol mimics which may link to the virus instead of raft cholesterol.
Both cyclodextrins and phytosterols could have health benefits, such as reduction of blood cholesterol levels, and are used to prevent and reduce the risk of coronary disease, to reduce inflammation, to induce apoptosis in cancer cells and also to treat viral infections. [11]
[1] Baglivo M, Baronio M, Natalini G, Beccari T, Chiurazzi P, Fulcheri E, Petralia PP, Michelini S, Fiorentini G, Miggiano GA, Morresi A, Tonini G, Bertelli M. (2020) Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity? Acta Biomed. 91(1):161 164. https://www.mattioli1885journals.com/index.php/actabiomedica/article/view/9402/8664.
[2] Heaton NS, Randall G. (2011) Multifaceted roles for lipids in viral infection. Trends Microbiol. 19(7):368-375. https://doi.org/10.1016/j.tim.2011.03.007
[3] Glende J, Schwegmann-wessels C, Al-falah M, et al. (2008) Importance of cholesterol-rich membrane microdomains in the interaction of the S protein of SARS-coronavirus with the cellular receptor angiotensin-converting enzyme 2. Virology. 381(2):215-221. https://doi.org/10.1016/j.virol.2008.08.026
[4] Jiang, Y., Liu, S., Shen, S., (…), Huang, H., Wei, W. (2020) Methyl-β-cyclodextrin inhibits EV-D68 virus entry by perturbing the accumulation of virus particles and ICAM-5 in lipid rafts. Antiviral Research 176,104752. https://doi.org/10.1016/j.antiviral.2020.104752
[5] Jeon, J.H., Lee, C. (2018) Cholesterol is important for the entry process of porcine deltacoronavirus. Archives of Virology 163(11), 3119-3124. https://doi.org/10.1007/s00705-018-3967-7
[6] Guo H, Huang M, Yuan Q, Wei Y, Gao Y, Mao L, et al. (2017) The Important Role of Lipid Raft-Mediated Attachment in the Infection of Cultured Cells by Coronavirus Infectious Bronchitis Virus Beaudette Strain. PLoS ONE 12(1): e0170123. https://doi.org/10.1371/journal.pone.0170123
[7] Takano, T., Satomi, Y., Oyama, Y., Doki, T., Hohdatsu, T. (2016) Differential effect of cholesterol on type I and II feline coronavirus infection. Archives of Virology 161(1), 125-133. https://doi.org/10.1007/s00705-015-2655-0
[8] Pratelli, A., Colao, V. (2015) Role of the lipid rafts in the life cycle of canine coronavirus. Journal of General Virology 96(2), 331-337. https://doi.org/10.1099/vir.0.070870-0
[9] Li G, Li Y, Yamate M. (2007) Lipid rafts play an important role in the early stage of severe acute respiratory syndrome-coronavirus life cycle. 9:96-102. https://doi.org/10.1016/j.micinf.2006.10.015
[10] Parvez MK, Rehman T, Alam P, Al-dosari MS, Alqasoumi SI, Alajmi MF. (2019) Plant-derived antiviral drugs as novel hepatitis B virus inhibitors : Cell culture and molecular docking study. Saudi Pharm J. 27(3):389-400. https://doi.org/10.1016/j.jsps.2018.12.008
[11] Oliva, A:F., Gonzalez, P.O., Risco, C. (2019) Targeting host lipid flows : Exploring new antiviral and antibiotic strategies. Cellular Microbiology 21, e12996. https://doi.org/10.1111/cmi.12996