Interaction of drugs with lipid raft membrane domains as a possible target

  • Hironori Tsuchiya Asahi University School of Dentistry, Mizuho, Gifu - Japan
  • Maki Mizogami Department of Anesthesiology, Kizawa Memorial Hospital, Minokamo, Gifu - Japan
Keywords: Drug target, Fluidity, Lipid raft, Membrane domain, Membrane interaction


Introduction: Plasma membranes are not the homogeneous bilayers of uniformly distributed lipids but the lipid complex with laterally separated lipid raft membrane domains, which provide receptor, ion channel and enzyme proteins with a platform. The aim of this article is to review the mechanistic interaction of drugs with membrane lipid rafts and address the question whether drugs induce physicochemical changes in raft-constituting and raft-surrounding membranes.

Methods: Literature searches of PubMed/MEDLINE and Google Scholar databases from 2000 to 2020 were conducted to include articles published in English in internationally recognized journals. Collected articles were independently reviewed by title, abstract and text for relevance.

Results: The literature search indicated that pharmacologically diverse drugs interact with raft model membranes and cellular membrane lipid rafts. They could physicochemically modify functional protein-localizing membrane lipid rafts and the membranes surrounding such domains, affecting the raft organizational integrity with the resultant exhibition of pharmacological activity. Raft-acting drugs were characterized as ones to decrease membrane fluidity, induce liquid-ordered phase or order plasma membranes, leading to lipid raft formation; and ones to increase membrane fluidity, induce liquid-disordered phase or reduce phase transition temperature, leading to lipid raft disruption.

Conclusion: Targeting lipid raft membrane domains would open a new way for drug design and development. Since angiotensin-converting enzyme 2 receptors which are a cell-specific target of and responsible for the cellular entry of novel coronavirus are localized in lipid rafts, agents that specifically disrupt the relevant rafts may be a drug against coronavirus disease 2019.


Kusumi A, Fujiwara TK, Chadda R, et al. Dynamic organizing principles of the plasma membrane that regulate signal transduction: commemorating the fortieth anniversary of Singer and Nicolson’s fluid-mosaic model. Annu Rev Cell Dev Biol. 2012;28(1):215-250. PMID:22905956

Pike LJ. Rafts defined: a report on the Keystone Symposium on Lipid Rafts and Cell Function. J Lipid Res. 2006;47(7):1597-1598. PMID:16645198

Hanzal-Bayer MF, Hancock JF. Lipid rafts and membrane traffic. FEBS Lett. 2007;581(11):2098-2104. PMID:17382322

McMullen T, Lewis R, McElhany R. Cholesterol-phospholipid interactions, the liquid-ordered phase and lipid rafts in model and biological membranes. Curr Opin Colloid Interface Sci. 2004;8(6):459-468.

Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000;1(1):31-39. PMID:11413487

Laude AJ, Prior IA. Plasma membrane microdomains: organization, function and trafficking. Mol Membr Biol. 2004;21(3):193-205.

George KS, Wu S. Lipid raft: A floating island of death or survival. Toxicol Appl Pharmacol. 2012;259(3):311-319. PMID:22289360

O’Connell KM, Martens JR, Tamkun MM. Localization of ion channels to lipid Raft domains within the cardiovascular system. Trends Cardiovasc Med. 2004;14(2):37-42. PMID:15030787

Maguy A, Hebert TE, Nattel S. Involvement of lipid rafts and caveolae in cardiac ion channel function. Cardiovasc Res. 2006;69(4):798-807.

Dalskov SM, Immerdal L, Niels-Christiansen LL, Hansen GH, Schousboe A, Danielsen EM. Lipid raft localization of GABA A receptor and Na+, K+-ATPase in discrete microdomain clusters in rat cerebellar granule cells. Neurochem Int. 2005;46(6):489-499. PMID:15769551

Patel HH, Murray F, Insel PA. G-protein-coupled receptor-signaling components in membrane raft and caveolae microdomains. Handb Exp Pharmacol. 2008;186(186):167-184. PMID:18491052

Xiang Y, Rybin VO, Steinberg SF, Kobilka B. Caveolar localization dictates physiologic signaling of β 2-adrenoceptors in neonatal cardiac myocytes. J Biol Chem. 2002;277(37):34280-34286. PMID:12097322

Pottosin II, Valencia-Cruz G, Bonales-Alatorre E, Shabala SN, Dobrovinskaya OR. Methyl-β-cyclodextrin reversibly alters the gating of lipid rafts-associated Kv1.3 channels in Jurkat T lymphocytes. Pflugers Arch. 2007;454(2):235-244.

Levitt ES, Clark MJ, Jenkins PM, Martens JR, Traynor JR. Differential effect of membrane cholesterol removal on μ- and δ-opioid receptors: a parallel comparison of acute and chronic signaling to adenylyl cyclase. J Biol Chem. 2009;284(33):22108-22122. PMID:19520863

Ding XQ, Fitzgerald JB, Matveev AV, McClellan ME, Elliott MH. Functional activity of photoreceptor cyclic nucleotide-gated channels is dependent on the integrity of cholesterol- and sphingolipid-enriched membrane domains. Biochemistry. 2008;47(12):3677-3687. PMID:18303857

Gandhavadi M, Allende D, Vidal A, Simon SA, McIntosh TJ. Structure, composition, and peptide binding properties of detergent soluble bilayers and detergent resistant rafts. Biophys J. 2002;82(3):1469-1482. PMID:11867462

Koumanov KS, Tessier C, Momchilova AB, Rainteau D, Wolf C, Quinn PJ. Comparative lipid analysis and structure of detergent-resistant membrane raft fractions isolated from human and ruminant erythrocytes. Arch Biochem Biophys. 2005;434(1):150-158. PMID:15629118

Holland GP, McIntyre SK, Alam TM. Distinguishing individual lipid headgroup mobility and phase transitions in raft-forming lipid mixtures with 31P MAS NMR. Biophys J. 2006;90(11):4248-4260. PMID:16533851

Simons K, Ehehalt R. Cholesterol, lipid rafts, and disease. J Clin Invest. 2002;110(5):597-603. PMID:12208858

Jacobson K, Mouritsen OG, Anderson RG. Lipid rafts: at a crossroad between cell biology and physics. Nat Cell Biol. 2007;9(1):7-14. PMID:17199125

Boesze-Battaglia K. Isolation of membrane rafts and signaling complexes. Methods Mol Biol. 2006;332:169-179. PMID:16878692

Loftsson T, Magnúsdóttir A, Másson M, Sigurjónsdóttir JF. Self-association and cyclodextrin solubilization of drugs. J Pharm Sci. 2002;91(11):2307-2316.

Mahammad S, Parmryd I. Cholesterol depletion using methyl-β-cyclodextrin. Methods Mol Biol. 2015;1232:91-102. PMID:25331130

Chau PL. New insights into the molecular mechanisms of general anaesthetics. Br J Pharmacol. 2010;161(2):288-307. PMID:20735416

Olsen RW, Li GD. GABA(A) receptors as molecular targets of general anesthetics: identification of binding sites provides clues to allosteric modulation. Can J Anaesth. 2011;58(2):206-215. PMID:21194017

Yamakura T, Harris RA. Effects of gaseous anesthetics nitrous oxide and xenon on ligand-gated ion channels. Comparison with isoflurane and ethanol. Anesthesiology. 2000;93(4):1095-1101. PMID:11020766

Daniell LC. Effect of anesthetic and convulsant barbiturates on N-methyl-D-aspartate receptor-mediated calcium flux in brain membrane vesicles. Pharmacology. 1994;49(5):296-307. PMID:7862741

Li X, Serwanski DR, Miralles CP, Bahr BA, De Blas AL. Two pools of Triton X-100-insoluble GABA(A) receptors are present in the brain, one associated to lipid rafts and another one to the post-synaptic GABAergic complex. J Neurochem. 2007;102(4):1329-1345. PMID:17663755

Parat MO. Could endothelial caveolae be the target of general anaesthetics? Br J Anaesth. 2006;96(5):547-550. PMID:16600902

Tsuchiya H. Structure-specific membrane-fluidizing effect of propofol. Clin Exp Pharmacol Physiol. 2001;28(4):292-299. PMID:11251643

Tsuchiya H, Ueno T, Tanaka T, Matsuura N, Mizogami M. Comparative study on determination of antioxidant and membrane activities of propofol and its related compounds. Eur J Pharm Sci. 2010;39(1-3):97-102. PMID:19897032

Gray E, Karslake J, Machta BB, Veatch SL. Liquid general anesthetics lower critical temperatures in plasma membrane vesicles. Biophys J. 2013;105(12):2751-2759. PMID:24359747

Grim KJ, Abcejo AJ, Barnes A, et al. Caveolae and propofol effects on airway smooth muscle. Br J Anaesth. 2012;109(3):444-453. PMID:22542538

Patel J, Chowdhury EA, Noorani B, Bickel U, Huang J. Isoflurane increases cell membrane fluidity significantly at clinical concentrations. Biochim Biophys Acta Biomembr. 2020;1862(2):183140. PMID:31790694

Turkyilmaz S, Almeida PF, Regen SL. Effects of isoflurane, halothane, and chloroform on the interactions and lateral organization of lipids in the liquid-ordered phase. Langmuir. 2011;27(23):14380-14385. PMID:21995557

Weinrich M, Nanda H, Worcester DL, Majkrzak CF, Maranville BB, Bezrukov SM. Halothane changes the domain structure of a binary lipid membrane. Langmuir. 2012;28(10):4723-4728. PMID:22352350

Weinrich M, Worcester DL. Xenon and other volatile anesthetics change domain structure in model lipid raft membranes. J Phys Chem B. 2013;117(50):16141-16147. PMID:24299622

Sierra-Valdez FJ, Ruiz-Suárez JC, Delint-Ramirez I. Pentobarbital modifies the lipid raft-protein interaction: A first clue about the anesthesia mechanism on NMDA and GABAA receptors. Biochim Biophys Acta. 2016;1858(11):2603-2610.

Fozzard HA, Lee PJ, Lipkind GM. Mechanism of local anesthetic drug action on voltage-gated sodium channels. Curr Pharm Des. 2005;11(21):2671-2686. PMID:16101448

Pristerá A, Okuse K. Building excitable membranes: lipid rafts and multiple controls on trafficking of electrogenic molecules. Neuroscientist. 2012;18(1):70-81. PMID:21518816

Bao L. Trafficking regulates the subcellular distribution of voltage-gated sodium channels in primary sensory neurons. Mol Pain. 2015;11:61.

Pristerà A, Baker MD, Okuse K. Association between tetrodotoxin resistant channels and lipid rafts regulates sensory neuron excitability. PLoS One. 2012;7(8):e40079. PMID:22870192

Kamata K, Manno S, Ozaki M, Takakuwa Y. Functional evidence for presence of lipid rafts in erythrocyte membranes: gsalpha in rafts is essential for signal transduction. Am J Hematol. 2008;83(5):371-375. PMID:18181202

Bandeiras C, Serro AP, Luzyanin K, Fernandes A, Saramago B. Anesthetics interacting with lipid rafts. Eur J Pharm Sci. 2013;48(1-2):153-165.

Yoshida K, Takashima A, Nishio I. Effect of dibucaine hydrochloride on raft-like lipid domains in model membrane system. MedChemComm. 2015;6(8):1444-1451.

Sugahara K, Shimokawa N, Takagi M. Thermal stability of phase-separated domains in multicomponent lipid membranes with local anesthetics. Membranes (Basel). 2017;7(3):33. PMID:28661445

Kinoshita M, Chitose T, Matsumori N. Mechanism of local anesthetic-induced disruption of raft-like ordered membrane domains. Biochim Biophys Acta, Gen Subj. 2019;1863(9):1381-1389. PMID:31207252

Groban L, Deal DD, Vernon JC, James RL, Butterworth J. Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs. Anesth Analg. 2001;92(1):37-43. PMID:11133597

Tsuchiya H, Ueno T, Mizogami M, Takakura K. Do local anesthetics interact preferentially with membrane lipid rafts? Comparative interactivities with raft-like membranes. J Anesth. 2010;24(4):639-642. PMID:20414686

Tsuchiya H, Mizogami M. R(+)-, Rac-, and S(-)-bupivacaine stereostructure-specifically interact with membrane lipids at cardiotoxically relevant concentrations. Anesth Analg. 2012;114(2):310-312. PMID:22156330

Pontier SM, Percherancier Y, Galandrin S, Breit A, Galés C, Bouvier M. Cholesterol-dependent separation of the β2-adrenergic receptor from its partners determines signaling efficacy: insight into nanoscale organization of signal transduction. J Biol Chem. 2008;283(36):24659-24672. PMID:18566454

Mizogami M, Takakura K, Tsuchiya H. The interactivities with lipid membranes differentially characterize selective and nonselective β1-blockers. Eur J Anaesthesiol. 2010;27(9):829-834. PMID:20601889

Tsuchiya H, Mizogami M. Characteristic interactivity of landiolol, an ultra-short-acting highly selective β1-blocker, with biomimetic membranes: comparisons with β1-selective esmolol and non-selective propranolol and alprenolol. Front Pharmacol. 2013;4:150. PMID:24339816

Prichard BN, Cruickshank JM, Graham BR. Beta-adrenergic blocking drugs in the treatment of hypertension. Blood Press. 2001;10(5-6):366-386.

Callera GE, Montezano AC, Yogi A, Tostes RC, Touyz RM. Vascular signaling through cholesterol-rich domains: implications in hypertension. Curr Opin Nephrol Hypertens. 2007;16(2):90-104. PMID:17293683

Mizogami M, Tsuchiya H. Membrane interactivity of anesthetic adjuvant dexmedetomidine discriminable from clonidine and enantiomeric levomedetomidine. J Adv Med Med Res. 2019;29:1-15.

Morris DP, Lei B, Wu YX, Michelotti GA, Schwinn DA. The α1a-adrenergic receptor occupies membrane rafts with its G protein effectors but internalizes via clathrin-coated pits. J Biol Chem. 2008;283(5):2973-2985. PMID:18048357

Huang P, Xu W, Yoon SI, et al. Agonist treatment did not affect association of mu opioid receptors with lipid rafts and cholesterol reduction had opposite effects on the receptor-mediated signaling in rat brain and CHO cells. Brain Res. 2007;1184:46-56. PMID:17980352

Heron DS, Shinitzky M, Zamir N, Samuel D. Adaptive modulations of brain membrane lipid fluidity in drug addiction and denervation supersensitivity. Biochem Pharmacol. 1982;31(14):2435-2438. PMID:6889866

Budai M, Szabó Z, Szogyi M, Gróf P. Molecular interactions between DPPC and morphine derivatives: a DSC and EPR study. Int J Pharm. 2003;250:239–250.

Zheng H, Chu J, Qiu Y, Loh HH, Law PY. Agonist-selective signaling is determined by the receptor location within the membrane domains. Proc Natl Acad Sci USA. 2008;105(27):9421-9426. PMID:18599439

Liou JY, Deng WG, Gilroy DW, Shyue SK, Wu KK. Colocalization and interaction of cyclooxygenase-2 with caveolin-1 in human fibroblasts. J Biol Chem. 2001;276(37):34975-34982. PMID:11432874

Alsop RJ, Toppozini L, Marquardt D, Kučerka N, Harroun TA, Rheinstädter MC. Aspirin inhibits formation of cholesterol rafts in fluid lipid membranes. Biochim Biophys Acta. 2015;1848(3):805-812. PMID:25475646

Alsop RJ, Himbert S, Dhaliwal A, Schmalzl K, Rheinstädter MC. Aspirin locally disrupts the liquid-ordered phase. R Soc Open Sci. 2018;5(2):171710.

Zhou Y, Cho KJ, Plowman SJ, Hancock JF. Nonsteroidal anti-inflammatory drugs alter the spatiotemporal organization of Ras proteins on the plasma membrane. J Biol Chem. 2012;287(20):16586-16595. PMID:22433858

Alves ACS, Dias RA, Kagami LP, et al. Beyond the “lock and key” paradigm: targeting lipid rafts to induce the selective apoptosis of cancer cells. Curr Med Chem. 2018;25(18):2082-2104. PMID:29332565

van der Luit AH, Vink SR, Klarenbeek JB, et al. A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells. Mol Cancer Ther. 2007;6(8):2337-2345. PMID:17699729

Alves AC, Ribeiro D, Nunes C, Reis S. Biophysics in cancer: the relevance of drug-membrane interaction studies. Biochim Biophys Acta. 2016;1858(9):2231-2244. PMID:27368477

Ausili A, Torrecillas A, Aranda FJ, et al. Edelfosine is incorporated into rafts and alters their organization. J Phys Chem B. 2008;112(37):11643-11654.

Gomide AB, Thomé CH, dos Santos GA, et al. Disrupting membrane raft domains by alkylphospholipids. Biochim Biophys Acta. 2013;1828(5):1384-1389. PMID:23376656

Castro BM, Fedorov A, Hornillos V, et al. Edelfosine and miltefosine effects on lipid raft properties: membrane biophysics in cell death by antitumor lipids. J Phys Chem B. 2013;117(26):7929-7940. PMID:23738749

Wnętrzak A, Łątka K, Makyła-Juzak K, Zemla J, Dynarowicz-Łątka P. The influence of an antitumor lipid - erucylphosphocholine - on artificial lipid raft system modeled as Langmuir monolayer. Mol Membr Biol. 2015;32(5-8):189-197. PMID:26911703

Węder K, Mach M, Hąc-Wydro K, Wydro P. Studies on the interactions of anticancer drug - Minerval - with membrane lipids in binary and ternary Langmuir monolayers. Biochim Biophys Acta Biomembr. 2018;1860(11):2329-2336. PMID:29864405

Rebillard A, Lagadic-Gossmann D, Dimanche-Boitrel MT. Cisplatin cytotoxicity: DNA and plasma membrane targets. Curr Med Chem. 2008;15(26):2656-2663. PMID:18991628

Lacour S, Hammann A, Grazide S, et al. Cisplatin-induced CD95 redistribution into membrane lipid rafts of HT29 human colon cancer cells. Cancer Res. 2004;64(10):3593-3598. PMID:15150117

Rebillard A, Tekpli X, Meurette O, et al. Cisplatin-induced apoptosis involves membrane fluidification via inhibition of NHE1 in human colon cancer cells. Cancer Res. 2007;67(16):7865-7874. PMID:17699793

Berquand A, Fa N, Dufrêne YF, Mingeot-Leclercq MP. Interaction of the macrolide antibiotic azithromycin with lipid bilayers: effect on membrane organization, fluidity, and permeability. Pharm Res. 2005;22(3):465-475. PMID:15835753

Alves AC, Ribeiro D, Horta M, Lima JLFC, Nunes C, Reis S. A biophysical approach to daunorubicin interaction with model membranes: relevance for the drug’s biological activity. J R Soc Interface. 2017;14(133):20170408. PMID:28855387

Alves AC, Magarkar A, Horta M, et al. Influence of doxorubicin on model cell membrane properties: insights from in vitro and in silico studies. Sci Rep. 2017;7(1):6343. PMID:28740256

Tsuchiya H. Membrane interactions of phytochemicals as their molecular mechanism applicable to the discovery of drug leads from plants. Molecules. 2015;20(10):18923-18966. PMID:26501254

1Tarahovsky YS, Kim YA, Yagolnik EA, Muzafarov EN. Flavonoid-membrane interactions: involvement of flavonoid-metal complexes in raft signaling. Biochim Biophys Acta. 2014;1838(5):1235-1246. PMID:24472512

Selvaraj S, Krishnaswamy S, Devashya V, Sethuraman S, Krishnan UM. Influence of membrane lipid composition on flavonoid-membrane interactions: implications on their biological activity. Prog Lipid Res. 2015;58:1-13.

Tarahovsky YS, Muzafarov EN, Kim YA. Rafts making and rafts braking: how plant flavonoids may control membrane heterogeneity. Mol Cell Biochem. 2008;314(1-2):65-71. PMID:18414995

Tsuchiya H, Mizogami M. Plant components exhibit pharmacological activities and drug interactions by acting on lipid membranes. Pharmacog Commun. 2012;2:58–71.

Psahoulia FH, Drosopoulos KG, Doubravska L, Andera L, Pintzas A. Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts. Mol Cancer Ther. 2007;6(9):2591-2599. PMID:17876056

Kaneko M, Takimoto H, Sugiyama T, Seki Y, Kawaguchi K, Kumazawa Y. Suppressive effects of the flavonoids quercetin and luteolin on the accumulation of lipid rafts after signal transduction via receptors. Immunopharmacol Immunotoxicol. 2008;30(4):867-882. PMID:18720166

Ionescu D, Margină D, Ilie M, Iftime A, Ganea C. Quercetin and epigallocatechin-3-gallate effect on the anisotropy of model membranes with cholesterol. Food Chem Toxicol. 2013;61:94-100. PMID:23523830

Tsuchiya H. Stereospecificity in membrane effects of catechins. Chem Biol Interact. 2001;134(1):41-54. PMID:11248221

Adachi S, Nagao T, Ingolfsson HI, et al. The inhibitory effect of (-)-epigallocatechin gallate on activation of the epidermal growth factor receptor is associated with altered lipid order in HT29 colon cancer cells. Cancer Res. 2007;67(13):6493-6501. PMID:17616711

Duhon D, Bigelow RL, Coleman DT, et al. The polyphenol epigallocatechin-3-gallate affects lipid rafts to block activation of the c-Met receptor in prostate cancer cells. Mol Carcinog. 2010;49(8):739-749. PMID:20623641

Tsukamoto S, Hirotsu K, Kumazoe M, et al. Green tea polyphenol EGCG induces lipid-raft clustering and apoptotic cell death by activating protein kinase Cδ and acid sphingomyelinase through a 67 kDa laminin receptor in multiple myeloma cells. Biochem J. 2012;443(2):525-534. PMID:22257159

Verstraeten SV, Oteiza PI, Fraga CG. Membrane effects of cocoa procyanidins in liposomes and Jurkat T cells. Biol Res. 2004;37(2):293-300. PMID:15455659

Verstraeten SV, Jaggers GK, Fraga CG, Oteiza PI. Procyanidins can interact with Caco-2 cell membrane lipid rafts: involvement of cholesterol. Biochim Biophys Acta. 2013;1828(11):2646-2653. PMID:23899501

Neves AR, Nunes C, Reis S. Resveratrol induces ordered domains formation in biomembranes: implication for its pleiotropic action. Biochim Biophys Acta. 2016;1858(1):12-18. PMID:26456556

Alves DS, Pérez-Fons L, Estepa A, Micol V. Membrane-related effects underlying the biological activity of the anthraquinones emodin and barbaloin. Biochem Pharmacol. 2004;68(3):549-561. PMID:15242821

Meng G, Liu Y, Lou C, Yang H. Emodin suppresses lipopolysaccharide-induced pro-inflammatory responses and NF-κB activation by disrupting lipid rafts in CD14-negative endothelial cells. Br J Pharmacol. 2010;161(7):1628-1644. PMID:20726986

Huang Q, Shen HM, Shui G, Wenk MR, Ong CN. Emodin inhibits tumor cell adhesion through disruption of the membrane lipid Raft-associated integrin signaling pathway. Cancer Res. 2006;66(11):5807-5815. PMID:16740720

Yi JS, Choo HJ, Cho BR, et al. Ginsenoside Rh2 induces ligand-independent Fas activation via lipid raft disruption. Biochem Biophys Res Commun. 2009;385(2):154-159. PMID:19445898

Wei Z, Wang J, Shi M, Liu W, Yang Z, Fu Y. Saikosaponin a inhibits LPS-induced inflammatory response by inducing liver X receptor alpha activation in primary mouse macrophages. Oncotarget. 2016;7(31):48995-49007.

Murai T. The role of lipid rafts in cancer cell adhesion and migration. Int J Cell Biol. 2012;2012:763283. PMID:22253629

Li YC, Park MJ, Ye SK, Kim CW, Kim YN. Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by cholesterol-depleting agents. Am J Pathol. 2006;168(4):1107-1118. PMID:16565487

Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46(4):586-590. PMID:32125455

Lu Y, Liu DX, Tam JP. Lipid rafts are involved in SARS-CoV entry into Vero E6 cells. Biochem Biophys Res Commun. 2008;369(2):344-349. PMID:18279660

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. PMID:18814896

Wang H, Yuan Z, Pavel MA, Hobson R, Hansen SB. The role of high cholesterol in age-related COVID19 lethality. bioRxiv. 2020.05.09.086249.

How to Cite
Tsuchiya H, Mizogami M. Interaction of drugs with lipid raft membrane domains as a possible target. DTI [Internet]. 22Dec.2020 [cited 22Jan.2021];14(1):34-7. Available from: