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Hardy, E.; Sarker, H.; Fernandez-Patron, C. Non-Cellular Molecular Interactome in the Blood Circulation. Encyclopedia. Available online: (accessed on 07 December 2023).
Hardy E, Sarker H, Fernandez-Patron C. Non-Cellular Molecular Interactome in the Blood Circulation. Encyclopedia. Available at: Accessed December 07, 2023.
Hardy, Eugenio, Hassan Sarker, Carlos Fernandez-Patron. "Non-Cellular Molecular Interactome in the Blood Circulation" Encyclopedia, (accessed December 07, 2023).
Hardy, E., Sarker, H., & Fernandez-Patron, C.(2023, June 28). Non-Cellular Molecular Interactome in the Blood Circulation. In Encyclopedia.
Hardy, Eugenio, et al. "Non-Cellular Molecular Interactome in the Blood Circulation." Encyclopedia. Web. 28 June, 2023.
Non-Cellular Molecular Interactome in the Blood Circulation

Much like artificial nanoparticles, relatively more complex biological entities with nanometric dimensions such as pathogens (viruses, bacteria, and other microorganisms) may also acquire a biomolecular corona upon entering the blood circulation of an organism. 

nanoparticles virus bacteria protein corona

1. Introduction

Any atomic/molecular assembly (nanoparticles, vaccine constructs) or pathogen (virus, bacteria, fungi, parasite) that is introduced to the blood circulation of an organism interacts with cellular and non-cellular (extracellular) components of the blood.
The innate immune system is an ancient form of host defence that has evolved over time to protect organisms from infection and damaged self [1][2]. There are two main types of innate immunity: constitutive and inducible. Constitutive innate immunity is considered the first line of defence against foreign pathogens and danger signals and includes physical barriers, cellular components (e.g., macrophages), and other components such as natural antibodies, acute phase proteins, the complement system, and the coagulation cascade [2]. Constitutive defences share common features, such as their manifestation at sites of constant interaction with pathogens, their destructive potential focused exclusively on the stimuli (e.g., microbes)—not on host cells or tissues, and their lack of potential to augment the innate immune response [3][4]. Most endogenous defence mechanisms are activated by infection, but some need specific recognition of the pathogen [3][4][5]. Inducible innate immunity generally involves pathogen-associated molecular patterns which are highly conserved molecular structures produced only by microorganisms (such as pathogenic microbes), but not by the host [3][4][5]. Upon recognition of pathogen-associated molecular patterns by receptors in cells of the innate immune system known as pattern-recognition receptors, a variety of signals such as costimulatory molecules, inflammatory cytokines, and chemokines are released that mediate a series of antimicrobial immune responses. These signals also activate and instruct the generation of pathogen-specific and sustained adaptive immune responses against persistent pathogens [3][4][5]. Innate mechanisms dependent on inducible pattern-recognition receptors can lead to very potent and effective protective responses, but also to excessive inflammatory and immunopathological reactions [5]. Although a wealth of published data exists on inducible innate responses mediated by pattern-recognition receptors that protect individuals from viral, bacterial, and parasitic infections, much remains to be understood about the constitutive immune mechanisms [5].

2. Artificial Nanoparticles and Their ‘Acquired Protein Coronas’

The term nanoparticle refers to any natural or artificial structure, including tubes and fibers, with external dimensions between 1 and 100 nanometers (nm) [6][7][8]. A spectrum of technologies enables nanoparticles to be manufactured and engineered with a specific synthetic (material-intrinsic) identity including rational coating of their surface to facilitate specific applications such as tissue targeting in biomedical applications [9][10][11][12]. For example, nanoparticles that have been covalently linked to macromolecules such as polyethylene glycol, antibodies, or peptides are designed to ensure desirable levels of solubility, stability, or biological activity in drug delivery.
One of the major aims in manipulating the surface properties of nanoparticles is to control their targeting and pharmacokinetics properties which are necessary for efficacious drug delivery [13][14]. When exposed to a physiological environment, such as the blood, nanoparticles interact with components of their environment. It is known that proteins in the blood convert naked nanoparticles into nanoparticles with a surface protein coat called a “protein corona” [15][16][17][18]. The formation of a protein corona on nanoparticles is mediated by mutual electrostatic and hydrophobic interactions, hydrogen bonding, van der Waals forces, or π-π stacking. The protein corona confers a new physical, chemical, and biological identity to the nanoparticles [17][18][19][20][21][22][23][24][25].
There is no universal protein corona; rather, each type of nanoparticle in a given environment acquires (i.e., adsorbs) a protein corona whose composition depends on the particle—and the environment. 
A protein that has been adsorbed to a nanoparticle can desorb from it or be replaced by another protein with a higher affinity [16][17][26]. The composition of the protein corona may thus evolve over time. A recent model postulates that the protein corona can form in a few seconds [16][20]. Further, nanoparticles carry proteins from one biological environment to another on their protein corona [16][20].
Much of the biological behavior of nanoparticles, including aggregation, circulation time, clearance rate, and targeting, are greatly influenced by the protein corona [9][15][19][21][27][28], which may include proteins involved in blood coagulation, immune responses including complement activation, and lipid transport. Protein coronas can concentrate proteins known as opsonins, such as complement proteins, coagulation proteins, and antibodies. Opsonins stimulate immune cell recognition and facilitate rapid clearance of nanoparticles from the bloodstream by immune cells such as macrophages [28][29][30][31][32][33]. Opsonic properties are also shared by proteins involved in lipid transport such as apolipoprotein A-I and apolipoprotein E [31]. Alpha-2-HS-glycoprotein can act as an opsonin, enhancing macrophage-deactivating mechanisms [34]. Apolipoproteins or other proteins with dysopsonin-like properties, such as histidine-rich glycoprotein, clusterin (apolipoprotein J), and albumin, which are present in protein coronas of nanoparticles, may prolong the time that nanoparticles circulate in blood [31].
Interestingly, protein coronas have also been identified on nanoparticles whose surface has been chemically modified, e.g., through the attachment of hydrophilic polymers such as polyethylene glycol, which is useful to lengthen blood circulation times and to decrease the hepatic uptake of the nanoparticles. Protein coronas have been described for nanoparticles both in vivo (as discussed) as well as in vitro.
Nanoparticles in biological environments including saliva, lung fluid, and blood have been found to interact with phospholipids, carbohydrates, nucleic acids, and other metabolites, in addition to proteins and peptides [9][35][36]. As a result, a layer of biomolecules (biocorona) may end up coating the nanoparticles’ surface giving nanoparticles a new biological identity [15][19][20][21][22][25][37]. Ultimately, the biocorona mediates interactions between the nanoparticle and the host biological system [19][20][21][22][23][38][39].

3. Nanoparticles Can Acquire Biocoronas: Do Viruses also Acquire a Biocorona?

Viral particles can have diverse shapes, including helical and icosahedral, and nanometric sizes (typically ranging from 20 to 300 nm) [40]. Apart from a nucleocapsid made of identical proteins (capsomers) enclosing the viral genome that can be RNA or DNA, viruses can have an envelope structure with phospholipids taken from host cells and pH-dependent surface charge [41]. In non-enveloped viruses, a coat protein controls the viral surface charge [42].
The recruitment of biocoronas described for artificial nanoparticles may be pervasive and affect the physico-chemical and biochemical potential of many structures, not just nanoparticles. Much like artificial nanoparticles in extracellular environments, viruses can attract layers of ions and molecules to their surface, including large biomolecules (e.g., proteins, peptides) and small biomolecules (e.g., metabolites such as lipids, steroids, or saccharides) that form a viral biocorona capable of influencing viral infectivity. In fact, phosphate and calcium ions from the surrounding intra- and extra-cellular media can bind to moieties on the viral surface, potentially changing the isoelectric point and overall surface charge of viral particles [42]. Antimicrobial peptides such as defensins (e.g., natural human neutrophil defensin 1-3, human defensin 5, and human β-defensin 3) can interact with glycoproteins from herpes simplex virus-1 and -2, thus affecting viral entry into host cells [43][44][45]. Distinct acquired coronas are displayed by different coronavirus variants [46].
The acquisition of a biocorona is expected to influence the viral particles’ behavior outside of host cells as well as virus–host cell interactions [46]. Rich and unique acquired biocoronas have been documented in herpes simplex virus type 1 and respiratory syncytial virus in various biological fluids to yield viral particle populations ranging from tens to a few hundreds of nanometers in size and diverse biocorona profiles [47]. Conceivably, these viral particles can be endocytosed by macrophages. Complement factors, properdin, protein S100, vimentin, and annexin A1 have been found in protein coronas of respiratory syncytial virus and may contribute to viral neutralization and/or influence viral infectivity as well as play roles in the modulation of the host immune response to the virus [47].

4. Cortisol and Dexamethasone Can Bind to Multiple Sites on SARS-CoV-2 S1: Could Glucocorticoids Be Components of Viral Biocoronas?

SARS-CoV-2 viral particles are approximately 60–140 nm in diameter and infect human cells through binding of the viral Spike protein (which is approximately 9 to 12 nm in length) to receptor proteins on the host cell surface [48]. Spike comprises two subunits, S1 and S2, which share an extracellular domain. The S1 subunit includes an N-terminal domain and receptor binding domain (RBD) which allow these coronaviruses to bind to host angiotensin converting enzyme 2 (ACE2 receptor) during virus entry into cells [49]. Clusters of differentiation 147 and 26 (CD147 and CD26 receptors) and transmembrane protease serine 2 (TMPRSS2 co-receptor) also participate in enabling the viral infection process [49][50].
SARS-CoV-2 can trigger the hypothalamic–pituitary–adrenal axis, leading to increased secretion of glucocorticoids from the adrenal cortex [51]. Once released, glucocorticoids circulate in the blood and contribute to the regulation of inflammatory signaling, systemic immune responses, and the metabolism of lipids and carbohydrates [52]. By binding to cytosolic/nuclear receptors, glucocorticoids can exert their effects through signal transduction pathways [52][53][54].
In contrast to the traditional view of the effects of glucocorticoids on cellular immunity, which is complex and cell-type specific [55][56], a new non-traditional view of the effects of endogenous glucocorticoids would be that constitutively secreted and SARS-CoV-2-induced glucocorticoids may be available to interact with viral components. Starting with in-silico studies (docking and molecular dynamics), researchers identified and validated unique pockets in SARS-CoV-2 S1 available for high-affinity binding of cortisol to S1, and concentration-dependent inhibition of the S1-ACE2 interaction [57]. These binding pockets are situated and distributed across the RBD, N-terminal domain, RBD–RBD interface, and N-terminal domain–RBD interface. Researchers used limited proteolysis coupled to liquid chromatography–mass spectrometry to confirm several of the cortisol-binding pockets identified by molecular dynamics (e.g., HCY_8, HCY_29, HCY_35, HCY_59, HCY_88, HCY_112, HCY_153, and HCY_161). Also, researchers determined the amino acid sequences to which cortisol binds. And corroborated cortisol-S1 interaction data with a cortisol-acetylcholinesterase conjugate assay, which showed that S1 can bind and scavenge free cortisol in solution and that binding of cortisol to S1 causes denaturation of S1, as shown using a GloMelt™ Thermal Shift Protein Stability [57]. Moreover, researchers found that nanomolar concentrations of cortisol inhibited the interaction between S1 and ACE2 [57]. Cortisol (100 nM) inhibited the interaction between the SARS-CoV-2 S1 Beta variant (E484K, K417N, N501Y) and ACE2 by ~55% inhibition. In contrast, some mutations in the Delta and Omicron variants of concern are located in or in the vicinity of cortisol-binding pockets and may reduce the effectiveness of cortisol binding to these variants of S1 [57]. As Spike mutations affecting cortisol binding to SARS-CoV-2 S1 could increase SARS-CoV-2 infectivity, cortisol interactions with S1 could be important for viral infectivity [51][57].
Researchers have proposed that the interactions between endogenous glucocorticoids and viral components such as S1 in SARS-CoV-2 may present a potentially novel innate immunity mechanism, through which glucocorticoids could participate in directly reducing viral infectivity [51][57]. A question that has not yet been experimentally addressed is whether there are other constitutive or viral-induced molecules in the human blood such as peptides and non-antibody proteins which define a non-cellular interactome cognate to structural components of SARS-CoV-2 (including S1) and capable of influencing SARS-CoV-2 infectivity either directly or in concert with glucocorticoids, such as cortisol.
When it comes to interactions with host factors, many viruses (including coronaviruses other than SARS-CoV-2) display similarities with artificial nanoparticles in that both can attract and become decorated by host factors found in extracellular environments. This should be unsurprising given the nanometric dimensions of viral particles.
In particular, the coronavirus particles, which range in size from 60 to 120 nm, have a viral surface made of a lipid bilayer (~85 nm in diameter) that is embedded with structural glycoproteins, including the membrane, envelope, and spike structural proteins [58][59]. Spike proteins, the component responsible for the surface’s crown-like appearance of coronaviruses (i.e., so named for their ‘inherited’ corona), are typically 20 nm long [60]. As with artificial nanoparticles, host proteins may be attracted to the surface of coronaviruses forming biomolecular coronas (‘acquired’ biocoronas) [46]. These acquired biocoronas can be as diverse as the dissimilar tissue microenvironments in which they develop and their different molecular compositions [46]. Mixed acquired biocoronas might result from the replacement of some molecular components of an initial biocorona with other biomolecules found in areas where coronaviruses are found, such as the circulation or body tissues [46]. Conceivably, the acquired corona can influence the interaction between the coronavirus and the host interrupting coronavirus binding through unconventional lung cell receptors, disrupting the lysosome’s capacity to break down invasive coronaviruses, biodistributing coronaviruses in various tissues, stimulating immune responses, and altering symptoms brought on by the coronavirus, as described for SARS-CoV-2 variants with altered acquired biocorona [46]. One example is human serum albumin, whose interactions with SARS-CoV-2 S1 may block antigenic sites on the RBD of S1, thus interfering with neutralizing antibodies with affinity for the RBD [61][62]. Another example is glucocorticoids. SARS-CoV-2 has 52 high-affinity glucocorticoid binding pockets on S1; the binding of cortisol to multiple sites on S1 decreases S1 affinity for ACE2 and may thus influence infectivity and disease severity. Conceivably, other molecules in the blood with affinity for S1 could influence (positively or negatively) cortisol affinity for S1 as well as S1 affinity for ACE2. This influence may be as diverse as competitive binding to cortisol pockets on S1, non-competitive binding to S1 regardless of whether cortisol is already bound or not, or non-competitive binding to preformed cortisol/S1 complexes.

5. Nanoparticles and Many Different Viruses Can Acquire Biocoronas: Do Pathogenic Bacteria and Other Microorganisms Acquire a Biocorona?

Bacterial cells, which range in size from 0.15 to 700 μm, can be thought of as colloidal particles [63]. The prokaryotic cell membrane is rich in cardiolipin and phosphatidylglycerol, which are glycerophospholipids with a net negative charge [64]. Teichoic and lipoteichoic acids as well as lipopolysaccharides are additional anionic membrane components on Gram-positive bacteria and Gram-negative bacteria, respectively [64]. The resultant negatively charged surface of many bacteria is known to attract positively charged antimicrobial peptides in blood, tears, saliva, and urine [65][66]. Depending on concentration, secondary structure, and physical-chemical characteristics (surface charge, hydrophobicity, and stability) of the lipid membrane, antimicrobial peptides can increase bacterial membrane permeability or result in structural damage followed by bacterial death [65][66][67][68][69]. In addition to antimicrobial peptides, a variety of antimicrobial proteins produced by tissues and innate immune cells are attracted to negatively charged surfaces of bacterial pathogens. Some of these host proteins serve as pattern-recognition receptors (extracellular soluble pattern-recognition molecules) for components on pathogenic bacteria [70]. Examples of these pattern-recognition molecules are conserved multimeric proteins called pentraxins (e.g., C-reactive protein and serum amyloid P), lectins such as collagen-like lectins known as collectins (e.g., mannose-binding lectin and surfactant protein A) and ficolins, and other complement molecules such as the complement component 1q and complement component C3b. Ficolin molecules contain a fibrinogen-like domain in addition to a collagen-like domain, and this domain has a particular affinity for N-acetylglucosamine [71].
Soluble pattern-recognition molecules in extracellular fluids are known to interact with pathogen-associated molecular patterns such as bacterial surface glycolipids and glycoproteins [68]. For instance, host C-reactive protein binds with high affinity to phosphocholine linked to bacterial polysaccharides as well as to phospholipids and glycans [72]. Serum amyloid P binds to phosphorylcholine, phosphatidylethanolamine, lipopolysaccharides, and bacterial surface sugars (e.g., galactose, mannose) [73][74][75]. Mannose-binding lectin binds to phospholipids, carbohydrates (mannose, N-acetylglucosamine), and non-glycosylated proteins [76]. Surfactant protein A binds N-acetyl mannosamine and bacterial phospholipids [77]. Collectins/ficolins bind to carbohydrate moieties displayed on bacterial surfaces through their carbohydrate-recognition (lectin) domains [71]. Ficolins typically bind to acetylated polysaccharides, including N-acetylgalactosamine and N-acetylglucosamine, and they may also interact with bacterial peptidoglycan, lipopolysaccharides, and sialic acid [78]. Complement component 1q can bind directly to pathogenic bacteria as well as to antigen–antibody (IgM, IgG1, and IgG3) complexes found on the bacteria surface [79][80]. C3b is a stable fragment derived from complement component 3 that covalently binds to bacterial lipopolysaccharides [81]. These well-known examples illustrate how the non-cellular blood interactome affects bacterial pathogens leading to the equivalent of an ‘acquired’ biocorona on the bacterial surface. There is a wealth of knowledge on the impact of bacteria–host interactions on bacterial pathogenicity. Soluble pattern-recognition molecules contribute to host innate immune defence mechanisms, such as complement activation and opsonization, which facilitate uptake by phagocytes, bacterial neutralization, and inflammation control.


  1. Kumar, H.; Kawai, T.; Akira, S. Pathogen Recognition by the Innate Immune System. Int. Rev. Immunol. 2011, 30, 16–34.
  2. Janeway, C.A.; Medzhitov, R. Innate Immune Recognition. Annu. Rev. Immunol. 2002, 20, 197–216.
  3. Medzhitov, R.; Janeway, C. Innate Immune Recognition: Mechanisms and Pathways. Immunol. Rev. 2000, 173, 89–97.
  4. Medzhitov, R.; Janeway, C. Innate Immunity. N. Engl. J. Med. 2000, 343, 338–344.
  5. Paludan, S.R.; Pradeu, T.; Masters, S.L.; Mogensen, T.H. Constitutive Immune Mechanisms: Mediators of Host Defence and Immune Regulation. Nat. Rev. Immunol. 2020, 21, 137–150.
  6. APTI (Air Pollution Training Institute). Module 3: Characteristics of Particles—Particle Size Categories. Basic Concepts in Environmental Sciences. USEPA (United States Environmental Protection Agency). “Less than 0.1 Microns”. Available online: (accessed on 10 April 2023).
  7. Vert, M.; Doi, Y.; Hellwich, K.H.; Hess, M.; Hodge, P.; Kubisa, P.; Rinaudo, M.; Schué, F. Terminology for Biorelated Polymers and Applications (IUPAC Recommendations 2012). Pure Appl. Chem. 2012, 84, 377–410.
  8. ISO/TS 80004-2: 2015—Nanotechnologies—Vocabulary—Part 2: Nano-Objects. Available online: (accessed on 10 April 2023).
  9. Fadeel, B. Understanding the Immunological Interactions of Engineered Nanomaterials: Role of the Bio-Corona. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2022, 14, e1798.
  10. Sun, Y.; Wang, X.; Fan, L.; Xie, X.; Miao, Z.; Ma, Y.; He, T.; Zha, Z. Facile Synthesis of Monodisperse Chromogenic Amylose-Iodine Nanoparticles as an Efficient Broad-Spectrum Antibacterial Agent. J. Mater. Chem. B 2020, 8, 3010–3015.
  11. Wang, X.; Shi, Q.; Zha, Z.; Zhu, D.; Zheng, L.; Shi, L.; Wei, X.; Lian, L.; Wu, K.; Cheng, L. Copper Single-Atom Catalysts with Photothermal Performance and Enhanced Nanozyme Activity for Bacteria-infected Wound Therapy. Bioact. Mater. 2021, 6, 4389.
  12. Wu, K.; Zhu, D.; Dai, X.; Wang, W.; Zhong, X.; Fang, Z.; Peng, C.; Wei, X.; Qian, H.; Chen, X.; et al. Bimetallic Oxide Cu1.5Mn1.5O4 Cage-like Frame Nanospheres with Triple Enzyme-like Activities for Bacterial-Infected Wound Therapy. Nanotoday 2022, 43, 101380.
  13. Manzari, M.T.; Shamay, Y.; Kiguchi, H.; Rosen, N.; Scaltriti, M.; Heller, D.A. Targeted Drug Delivery Strategies for Precision Medicines. Nat. Rev. Mater. 2021, 6, 351–370.
  14. Mitchell, M.J.; Billingsley, M.M.; Haley, R.M.; Wechsler, M.E.; Peppas, N.A.; Langer, R. Engineering Precision Nanoparticles for Drug Delivery. Nat. Rev. Drug Discov. 2020, 20, 101–124.
  15. Monopoli, M.P.; Åberg, C.; Salvati, A.; Dawson, K.A. Biomolecular Coronas Provide the Biological Identity of Nanosized Materials. Nat. Nanotechnol. 2012, 7, 779–786.
  16. Tenzer, S.; Docter, D.; Kuharev, J.; Musyanovych, A.; Fetz, V.; Hecht, R.; Schlenk, F.; Fischer, D.; Kiouptsi, K.; Reinhardt, C.; et al. Rapid Formation of Plasma Protein Corona Critically Affects Nanoparticle Pathophysiology. Nat. Nanotechnol. 2013, 8, 772–781.
  17. Nel, A.E.; Mädler, L.; Velegol, D.; Xia, T.; Hoek, E.M.V.; Somasundaran, P.; Klaessig, F.; Castranova, V.; Thompson, M. Understanding Biophysicochemical Interactions at the Nano-Bio Interface. Nat. Mater. 2009, 8, 543–557.
  18. Champion, J.A.; Pustulka, S.M.; Ling, K.; Pish, S.L. Protein Nanoparticle Charge and Hydrophobicity Govern Protein Corona and Macrophage Uptake. ACS Appl. Mater. Interfaces 2020, 12, 48284–48295.
  19. Corbo, C.; Molinaro, R.; Parodi, A.; Toledano Furman, N.E.; Salvatore, F.; Tasciotti, E. The Impact of Nanoparticle Protein Corona on Cytotoxicity, Immunotoxicity and Target Drug Delivery. Nanomedicine 2016, 11, 81–100.
  20. Docter, D.; Strieth, S.; Westmeier, D.; Hayden, O.; Gao, M.; Knauer, S.K.; Stauber, R.H. No King without a Crown—Impact of the Nanomaterial-Protein Corona on Nanobiomedicine. Nanomedicine 2015, 10, 503–519.
  21. Ke, P.C.; Lin, S.; Parak, W.J.; Davis, T.P.; Caruso, F. A Decade of the Protein Corona. ACS Nano 2017, 11, 11773–11776.
  22. Docter, D.; Westmeier, D.; Markiewicz, M.; Stolte, S.; Knauer, S.K.; Stauber, R.H. The Nanoparticle Biomolecule Corona: Lessons Learned—Challenge Accepted? Chem. Soc. Rev. 2015, 44, 6094–6121.
  23. Farrera, C.; Fadeel, B. It Takes Two to Tango: Understanding the Interactions between Engineered Nanomaterials and the Immune System. Eur. J. Pharm. Biopharm. 2015, 95, 3–12.
  24. Francia, V.; Yang, K.; Deville, S.; Reker-Smit, C.; Nelissen, I.; Salvati, A. Corona Composition Can Affect the Mechanisms Cells Use to Internalize Nanoparticles. ACS Nano 2019, 13, 11107–11121.
  25. Ren, J.; Andrikopoulos, N.; Velonia, K.; Tang, H.; Cai, R.; Ding, F.; Ke, P.C.; Chen, C. Chemical and Biophysical Signatures of the Protein Corona in Nanomedicine. J. Am. Chem. Soc. 2022, 144, 9184–9205.
  26. Casals, E.; Pfaller, T.; Duschl, A.; Oostingh, G.J.; Puntes, V. Time Evolution of the Nanoparticle Protein Corona. ACS Nano 2010, 4, 3623–3632.
  27. Dilliard, S.A.; Siegwart, D.J. Passive, Active and Endogenous Organ-Targeted Lipid and Polymer Nanoparticles for Delivery of Genetic Drugs. Nat. Rev. Mater. 2023, 8, 282.
  28. Berardi, A.; Baldelli Bombelli, F. Oral Delivery of Nanoparticles—Let’s Not Forget about the Protein Corona. Expert Opin. Drug Deliv. 2019, 16, 563–566.
  29. Nguyen, V.H.; Lee, B.J. Protein Corona: A New Approach for Nanomedicine Design. Int. J. Nanomed. 2017, 12, 3137–3151.
  30. Wang, Y.-F.; Zhou, Y.; Sun, J.; Wang, X.; Jia, Y.; Ge, K.; Yan, Y.; Dawson, K.A.; Guo, S.; Zhang, J.; et al. The Yin and Yang of the Protein Corona on the Delivery Journey of Nanoparticles. Nano Res. 2023, 16, 715–734.
  31. Papini, E.; Tavano, R.; Mancin, F. Opsonins and Dysopsonins of Nanoparticles: Facts, Concepts, and Methodological Guidelines. Front. Immunol. 2020, 11, 567365.
  32. Moein Moghimi, S.; Patel, H.M. Serum Opsonins and Phagocytosis of Saturated and Unsaturated Phospholipid Liposomes. BBA-Biomembr. 1989, 984, 384–387.
  33. Tavano, R.; Gabrielli, L.; Lubian, E.; Fedeli, C.; Visentin, S.; Polverino De Laureto, P.; Arrigoni, G.; Geffner-Smith, A.; Chen, F.; Simberg, D.; et al. C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-Methyl-2-Oxazoline)-Coated Silica Nanoparticles by Human Phagocytes. ACS Nano 2018, 12, 5834–5847.
  34. Wang, H.; Zhang, M.; Bianchi, M.; Sherry, B.; Sama, A.; Tracey, K.J. Fetuin (Alpha2-HS-Glycoprotein) Opsonizes Cationic Macrophagedeactivating Molecules. Proc. Natl. Acad. Sci. USA 1998, 95, 14429–14434.
  35. Abarca-Cabrera, L.; Fraga-García, P.; Berensmeier, S. Bio-Nano Interactions: Binding Proteins, Polysaccharides, Lipids and Nucleic Acids onto Magnetic Nanoparticles. Biomater. Res. 2021, 25, 12.
  36. Abarca-Cabrera, L.; Xu, L.; Berensmeier, S.; Fraga-García, P. Competition at the Bio-Nano Interface: A Protein, a Polysaccharide, and a Fatty Acid Adsorb onto Magnetic Nanoparticles. ACS Appl. Bio Mater. 2023, 6, 146–156.
  37. Lynch, I.; Cedervall, T.; Lundqvist, M.; Cabaleiro-Lago, C.; Linse, S.; Dawson, K.A. The Nanoparticle-Protein Complex as a Biological Entity; a Complex Fluids and Surface Science Challenge for the 21st Century. Adv. Colloid Interface Sci. 2007, 134–135, 167–174.
  38. Al-Ahmady, Z.S.; Hadjidemetriou, M.; Gubbins, J.; Kostarelos, K. Formation of Protein Corona in Vivo Affects Drug Release from Temperature-Sensitive Liposomes. J. Control Release 2018, 276, 157–167.
  39. Fasoli, E. Protein Corona: Dr. Jekyll and Mr. Hyde of Nanomedicine. Biotechnol. Appl. Biochem. 2021, 68, 1139–1152.
  40. Pellett, P.E.; Mitra, S.; Holland, T.C. Basics of Virology. Handb. Clin. Neurol. 2014, 123, 45.
  41. Michen, B.; Graule, T. Isoelectric Points of Viruses. J. Appl. Microbiol. 2010, 109, 388–397.
  42. Heffron, J.; Mayer, B.K. Virus Isoelectric Point Estimation: Theories and Methods. Appl. Environ. Microbiol. 2021, 87, e02319-20.
  43. Wilson, S.S.; Wiens, M.E.; Smith, J.G. Antiviral Mechanisms of Human Defensins. J. Mol. Biol. 2013, 425, 4965–4980.
  44. Hazrati, E.; Galen, B.; Lu, W.; Wang, W.; Ouyang, Y.; Keller, M.J.; Lehrer, R.I.; Herold, B.C. Human Alpha- and Beta-Defensins Block Multiple Steps in Herpes Simplex Virus Infection. J. Immunol. 2006, 177, 8658–8666.
  45. Rapista, A.; Ding, J.; Benito, B.; Lo, Y.T.; Neiditch, M.B.; Lu, W.; Chang, T.L. Human Defensins 5 and 6 Enhance HIV-1 Infectivity through Promoting HIV Attachment. Retrovirology 2011, 8, 45.
  46. Gao, J.; Zeng, L.; Yao, L.; Wang, Z.; Yang, X.; Shi, J.; Hu, L.; Liu, Q.; Chen, C.; Xia, T.; et al. Inherited and Acquired Corona of Coronavirus in the Host: Inspiration from the Biomolecular Corona of Nanoparticles. Nano. Today 2021, 39, 101161.
  47. Ezzat, K.; Pernemalm, M.; Pålsson, S.; Roberts, T.C.; Järver, P.; Dondalska, A.; Bestas, B.; Sobkowiak, M.J.; Levänen, B.; Sköld, M.; et al. The Viral Protein Corona Directs Viral Pathogenesis and Amyloid Aggregation. Nat. Commun. 2019, 10, 2331.
  48. Bar-On, Y.M.; Flamholz, A.; Phillips, R.; Milo, R. SARS-CoV-2 (COVID-19) by the Numbers. eLife 2020, 9, e57309.
  49. Tay, M.Z.; Poh, C.M.; Rénia, L.; MacAry, P.A.; Ng, L.F.P. The Trinity of COVID-19: Immunity, Inflammation and Intervention. Nat. Rev. Immunol. 2020, 20, 363–374.
  50. Wang, L.; Wang, Y.; Ye, D.; Liu, Q. Review of the 2019 Novel Coronavirus (SARS-CoV-2) Based on Current Evidence. Int. J. Antimicrob. Agents 2020, 55, 105948.
  51. Hardy, E.; Fernandez-Patron, C. Could Endogenous Glucocorticoids Influence SARS-CoV-2 Infectivity? Cells 2022, 11, 2955.
  52. Stahn, C.; Buttgereit, F. Genomic and Nongenomic Effects of Glucocorticoids. Nat. Clin. Pract. Rheumatol. 2008, 4, 525–533.
  53. Chrousos, G.P.; Kino, T. Glucocorticoid Action Networks and Complex Psychiatric and/or Somatic Disorders. Stress 2007, 10, 213–219.
  54. Taves, M.D.; Gomez-Sanchez, C.E.; Soma, K.K. Extra-Adrenal Glucocorticoids and Mineralocorticoids: Evidence for Local Synthesis, Regulation, and Function. Am. J. Physiol. Endocrinol. Metab. 2011, 301, E11–E24.
  55. Shimba, A.; Ikuta, K. Control of Immunity by Glucocorticoids in Health and Disease. Semin. Immunopathol. 2020, 42, 669–680.
  56. Shimba, A.; Ikuta, K. Immune-Enhancing Effects of Glucocorticoids in Response to Day-Night Cycles and Stress. Int. Immunol. 2020, 32, 703–708.
  57. Sarker, H.; Panigrahi, R.; Hardy, E.; Glover, J.N.M.; Elahi, S.; Fernandez-Patron, C. Glucocorticoids Bind to SARS-CoV-2 S1 at Multiple Sites Causing Cooperative Inhibition of SARS-CoV-2 S1 Interaction with ACE2. Front. Immunol. 2022, 13, 2833.
  58. Fehr, A.R.; Perlman, S. Coronaviruses: An Overview of Their Replication and Pathogenesis. Methods Mol. Biol. 2015, 1282, 1–23.
  59. Ziebuhr, J. Molecular Biology of Severe Acute Respiratory Syndrome Coronavirus. Curr. Opin. Microbiol. 2004, 7, 412–419.
  60. Bosch, B.J.; van der Zee, R.; de Haan, C.A.M.; Rottier, P.J.M. The Coronavirus Spike Protein Is a Class I Virus Fusion Protein: Structural and Functional Characterization of the Fusion Core Complex. J. Virol. 2003, 77, 8801.
  61. Yin, Y.; Sheng, Y.; Wang, M.; Ni, S.; Ding, H.; Ma, Y. Protein Corona Critically Affects the Bio-Behaviors of SARS-CoV-2. arXiv 2021, arXiv:2102.05440.
  62. Iles, J.; Zmuidinaite, R.; Sadee, C.; Gardiner, A.; Lacey, J.; Harding, S.; Ule, J.; Roblett, D.; Heeney, J.; Baxendale, H.; et al. SARS-CoV-2 Spike Protein Binding of Glycated Serum Albumin-Its Potential Role in the Pathogenesis of the COVID-19 Clinical Syndromes and Bias towards Individuals with Pre-Diabetes/Type 2 Diabetes and Metabolic Diseases. Int. J. Mol. Sci. 2022, 23, 4126.
  63. Weiser, J.N. The Battle with the Host over Microbial Size. Curr. Opin. Microbiol. 2013, 16, 59–62.
  64. Sohlenkamp, C.; Geiger, O. Bacterial Membrane Lipids: Diversity in Structures and Pathways. FEMS Microbiol. Rev. 2016, 40, 133–159.
  65. Bastos, P.; Trindade, F.; da Costa, J.; Ferreira, R.; Vitorino, R. Human Antimicrobial Peptides in Bodily Fluids: Current Knowledge and Therapeutic Perspectives in the Postantibiotic Era. Med. Res. Rev. 2018, 38, 101–146.
  66. Bechinger, B.; Gorr, S.U. Antimicrobial Peptides: Mechanisms of Action and Resistance. J. Dent. Res. 2017, 96, 254–260.
  67. Lei, J.; Sun, L.C.; Huang, S.; Zhu, C.; Li, P.; He, J.; Mackey, V.; Coy, D.H.; He, Q.Y. The Antimicrobial Peptides and Their Potential Clinical Applications. Am. J. Transl. Res. 2019, 11, 3919.
  68. Huan, Y.; Kong, Q.; Mou, H.; Yi, H. Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields. Front. Microbiol. 2020, 11, 582779.
  69. Giangaspero, A.; Sandri, L.; Tossi, A. Amphipathic Alpha Helical Antimicrobial Peptides. Eur. J. Biochem. 2001, 268, 5589–5600.
  70. Li, D.; Wu, M. Pattern Recognition Receptors in Health and Diseases. Signal Transduct. Target. Ther. 2021, 6, 291.
  71. Howard, M.; Farrar, C.A.; Sacks, S.H. Structural and Functional Diversity of Collectins and Ficolins and Their Relationship to Disease. Semin. Immunopathol. 2018, 40, 75–85.
  72. Pepys, M.B.; Hirschfield, G.M. C-Reactive Protein: A Critical Update. J. Clin. Investig. 2003, 111, 1805–1812.
  73. Pepys, M.B.; Booth, D.R.; Hutchinson, W.L.; Gallimore, J.R.; Collins, P.M.; Hohenester, E. Amyloid P Component. A Critical Review. J. Protein Fold. Disord. 1997, 4, 274–295.
  74. Clos, T.W. Du Pentraxins: Structure, Function, and Role in Inflammation. ISRN Inflamm. 2013, 2013, 379040.
  75. Schwalbe, R.A.; Nelsestuen, G.L.; Dahlbáck, B.; Coe, J.E. Pentraxin Family of Proteins Interact Specifically with Phosphorylcholine and/or Phosphorylethanolamine. Biochemistry 1992, 31, 4907–4915.
  76. Dommett, R.M.; Klein, N.; Turner, M.W. Mannose-Binding Lectin in Innate Immunity: Past, Present and Future. Tissue Antigens 2006, 68, 193–209.
  77. Kingma, P.; Jobe, A.H. The Surfactant System. In Kendig’s Disorders of the Respiratory Tract in Children; Elsevier: Amsterdam, The Netherlands, 2019; pp. 57–62.e2.
  78. Bidula, S.; Sexton, D.W.; Schelenz, S. Ficolins and the Recognition of Pathogenic Microorganisms: An Overview of the Innate Immune Response and Contribution of Single Nucleotide Polymorphisms. J. Immunol. Res. 2019, 2019, 3205072.
  79. Reid, K.B.M. Complement Component C1q: Historical Perspective of a Functionally Versatile, and Structurally Unusual, Serum Protein. Front. Immunol. 2018, 9, 764.
  80. Kishore, U.; Ghai, R.; Greenhough, T.J.; Shrive, A.K.; Bonifati, D.M.; Gadjeva, M.G.; Waters, P.; Kojouharova, M.S.; Chakraborty, T.; Agrawal, A. Structural and Functional Anatomy of the Globular Domain of Complement Protein C1q. Immunol. Lett. 2004, 95, 113–128.
  81. Elsevier. Complement. In Immunology for Pharmacy; Elsevier: Amsterdam, The Netherlands, 2012; pp. 87–96.
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