Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity? SARS-COV-2 lipid-dependent attachment to host cells

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Mirko Baglivo
Manuela Baronio
Giuseppe Natalini
Tommaso Beccari
Pietro Chiurazzi
Ezio Fulcheri
Paolo Pietro Petralia
Sandro Michelini
Giovanni Fiorentini
Giacinto Abele Miggiano
Assunta Morresi
Gerolamo Tonini
Matteo Bertelli


Coronavirus, Sars-cov-2, Lipid raft, cholesterol, phytosterol


Background: Viral infectivity depends on interactions between components of the host cell plasma membrane and the virus envelope. Here we review strategies that could help stem the advance of the SARS-COV-2 epidemic. Methods and Results: We focus on the role of lipid structures, such as lipid rafts and cholesterol, involved in the process, mediated by endocytosis, by which viruses attach to and infect cells. Previous studies have shown that many naturally derived substances, such as cyclodextrin and sterols, could reduce the infectivity of many types of viruses, including the coronavirus family, through interference with lipid-dependent attachment to human host cells. Conclusions: Certain molecules prove able to reduce the infectivity of some coronaviruses, possibly by inhibiting viral lipid-dependent attachment to host cells. More research into these molecules and methods would be worthwhile as it could provide insights the mechanism of transmission of SARS-COV-2 and, into how they could become a basis for new antiviral strategies.


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1. Yan R, Yan R, Zhang Y, et al. Structural basis for the recognition of the SARS-CoV-2 by. 2020;2762(March):1-10.
2. Zhou P, Yang X, Wang X, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(January). doi:10.1038/s41586-020-2012-7
3. Corman VM, Landt O, Kaiser M, et al. Detection of 2019 novel coronavirus ( 2019-nCoV ) by. 2019;(December):1-8.
4. Kannan S, Ali PSS, Sheeza A, Hemalatha K. COVID-19 ( Novel Coronavirus 2019 ) – recent trends. 2020;19:2006-2011.
5. Heaton NS, Randall G. Multifaceted roles for lipids in viral infection. Trends Microbiol. 2011;19(7):368-375. doi:10.1016/j.tim.2011.03.007
6. Lajoie P, Nabi IR. Regulation of raft-dependent endocytosis. 2007;11(4):644-653. doi:10.1111/j.1582-4934.2007.00083.x
7. Tang Q, Liu P, Chen M. Virion-Associated Cholesterol Regulates the Infection of Human Parainfluenza Virus Type 3. 2019.
8. Glende J, Schwegmann-wessels C, Al-falah M, et al. 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. 2008;381(2):215-221. doi:10.1016/j.virol.2008.08.026
9. Wei X, She G, Wu T, Xue C, Cao Y. PEDV enters cells through clathrin ‑, caveolae ‑, and lipid raft ‑ mediated endocytosis and traffics via the endo ‑/ lysosome pathway. Vet Res. 2020:1-18. doi:10.1186/s13567-020-0739-7
10. Thorp EB, Gallagher TM. Requirements for CEACAMs and Cholesterol during Murine Coronavirus Cell Entry. (29).
11. Choi KS, Aizaki H, Lai MMC. Murine Coronavirus Requires Lipid Rafts for Virus Entry and Cell-Cell Fusion but Not for Virus Release. 2011;79(15):9862-9871. doi:10.1128/JVI.79.15.9862
12. Cervin M, Anderson R. Modulation of Coronavirus-Mediated Cell Fusion by Homeostatic Control of Cholesterol and Fatty Acid Metabolism. 1991;149:142-149.
13. Daya M, Anderson R. Cholesterol Enhances Mouse Hepatitis Virus-Mediated Cell Fusion. 1999;283(1988):276-283.
14. Li G, Li Y, Yamate M. Lipid rafts play an important role in the early stage of severe acute respiratory syndrome-coronavirus life cycle. 2007;9:96-102. doi:10.1016/j.micinf.2006.10.015
15. Guo H, Huang M, Yuan Q, et al. The Important Role of Lipid Raft-Mediated Attachment in the Infection of Cultured Cells by Coronavirus Infectious Bronchitis Virus Beaudette Strain. 2017:1-12. doi:10.1371/journal.pone.0170123
16. Cagno V, Tintori C, Civra A, et al. Novel broad spectrum virucidal molecules against enveloped viruses. 2018:1-18. doi:10.6084/m9.figshare.6854165.Funding
17. Cagno V, Andreozzi P, Alicarnasso MD, et al. with a virucidal inhibition mechanism. 2017;(December):1-10. doi:10.1038/NMAT5053
18. Zidovetzki R, Levitan I. Use of cyclodextrins to manipulate plasma membrane cholesterol content: evidence, misconceptions and control strategies. Biochim Biophys Acta. 2007; 1768(6):1311-1324.
19. Fenyvesi VA, An JS, Csabai K, Malanga M, Szente L. Methyl-Beta-Cyclodextrins : The Role of Number and Types of Substituents in Solubilizing Power. 2014:1443-1452. doi:10.1002/jps.23917
20. Verma SP. HIV : A Raft-Targeting Approach for Prevention and Therapy Using Plant-Derived Compounds ( Review ). 2009;2:51-59.
21. Gujjeti R.P. Anti-HIV Activity of Phytosterol Isolated from Aerva lanata Roots. Pharmacogn J. 2017;9(1):112-116.
22. Parvez MK, Rehman T, Alam P, Al-dosari MS, Alqasoumi SI, Alajmi MF. Plant-derived antiviral drugs as novel hepatitis B virus inhibitors : Cell culture and molecular docking study. Saudi Pharm J. 2019;27(3):389-400. doi:10.1016/j.jsps.2018.12.008
23. Sigler K. Sterols and Triterpenoids with Antiviral Activity. 2009;(June 2015). doi:10.2174/187152109788680207
24. Abumweis SS, Barake R, Jones PJH. randomized controlled trials. 2008;1:1-17. doi:10.3402/fnr.v52i0.1811
25. Proc MC, Stanols P, Nutrition H, Wash- F, Unilever N V, Foods F. Management of Blood Cholesterol Levels. 2003;78(August):965-978. doi:10.4065/78.8.965
26. Gironi B, Oliva R, Petraccone L, et al. BBA - Biomembranes Solvation properties of raft-like model membranes. BBA - Biomembr. 2019;1861(11):183052. doi:10.1016/j.bbamem.2019.183052
27. Pollock S, Branza N, Böhmer A, Radulescu C, Dwek RA. Polyunsaturated liposomes are antiviral against hepatitis B and C viruses and HIV by decreasing cholesterol levels in infected cells. 2010. doi:10.1073/pnas.1009445107/-/
28. Oliva AF, Risco C. Targeting host lipid flows : Exploring new antiviral and antibiotic strategies. 2019;(December 2018):1-17. doi:10.1111/cmi.12996

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