A Multifunctional Neutralizing Antibody‐Conjugated Nanoparticle Inhibits and Inactivates SARS‐CoV‐2

Abstract

The outbreak of 2019 coronavirus disease (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has resulted in a global pandemic. Despite intensive research, the current treatment options show limited curative efficacies. Here the authors report a strategy incorporating neutralizing antibodies conjugated to the surface of a photothermal nanoparticle (NP) to capture and inactivate SARS‐CoV‐2. The NP is comprised of a semiconducting polymer core and a biocompatible polyethylene glycol surface decorated with high‐affinity neutralizing antibodies. The multifunctional NP efficiently captures SARS‐CoV‐2 pseudovirions and completely blocks viral infection to host cells in vitro through the surface neutralizing antibodies. In addition to virus capture and blocking function, the NP also possesses photothermal function to generate heat following irradiation for inactivation of virus. Importantly, the NPs described herein significantly outperform neutralizing antibodies at treating authentic SARS‐CoV‐2 infection in vivo. This multifunctional NP provides a flexible platform that can be readily adapted to other SARS‐CoV‐2 antibodies and extended to novel therapeutic proteins, thus it is expected to provide a broad range of protection against original SARS‐CoV‐2 and its variants.

Behavior of Citrate-Capped Ultrasmall Gold Nanoparticles on a Supported Lipid Bilayer Interface at Atomic Resolution

“…The inability of the AuNP to successfully embed completely within the gel-phase bilayer (i.e., interfacial interaction) has potential implications for other hard–soft matter or lipid–NP interactions and other biological–bilayer interactions, as other materials with similar properties may exhibit similar behavior. The ability of the AuNP to localize within the central core of the fluid-phase bilayer has potential applications in targeting specific membrane embedded protein anchorage motifs (i.e., nonpolar/hydrophobic regions of proteins). , Specificity of these domains and functionality can be further enhanced via AuNP–protein/peptide conjugation, − while cell penetration can be enhanced via alteration of ligand coating and conjugation to cell-penetrating peptides . The ability of the AuNP to potentially translocate across the gel-phase bilayer upper leaflet surface allows it to potentially illicit effects and/or delivery compounds to the cell without direct interference with intracellular organelles or other cellular constituents.…”

Nanoscale Technologies in the Fight against COVID-19: From Innovative Nanomaterials to Computer-Aided Discovery of Potential Antiviral Plant-Derived Drugs

“…Among them, a successful approach might be represented by using photothermal NPs, due to the heat sensitivity of SARS-CoV-2 ( Figure 15 ). This interesting approach finalized to capture and inactivate SARS-CoV-2 has been adopted by Cai et al [ 191 ]. The researchers prepared a nanosystem based on neutralizing antibodies conjugated on the surface of photothermal multifunctional NPs, prepared through self-assembly of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N [carboxy(polyethyleneglycol)-2000, NHS ester] (DSPE-PEG2000-NHS) (to form an amphiphilic polymer shell) and poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b’]dithiophene)-alt-4,7(2,1,3-benzothiadiazole)] (PCPDTBT) (to form a semiconducting polymer core), and functionalized with an anti-SARS-CoV-2 neutralizing antibody (IgG2b), covalently attached to the NP surface by the NHS ester coupling.…”

Discovery of a Phage Peptide Specifically Binding to the SARS-CoV-2 Spike S1 Protein for the Sensitive Phage-Based Enzyme-Linked Chemiluminescence Immunoassay of the SARS-CoV-2 Antigen

“… 5 The S protein consists of two subunits: the S1 subunit is composed of the N-terminal domain (NTD) and receptor binding domain (RBD), which binds to cells expressing viral receptors, while the S2 subunit mediates fusion between the virus and the cell membrane. 6 , 7 S protein is an abundant viral transmembrane protein, and the amino acid sequence of this glycoprotein is different from other coronaviruses, so S protein is a suitable target protein for selective recognition of SARS-CoV-2.…”

“…There are four main proteins encoded by the SARS-CoV-2 genome: spike (S) protein, nucleocapsid (N) protein, membrane (M) protein, and envelope (E) protein. , Among them, the S protein is a type I fusion protein and plays an important role in the process of virus infection and pathogenesis . The S protein consists of two subunits: the S1 subunit is composed of the N-terminal domain (NTD) and receptor binding domain (RBD), which binds to cells expressing viral receptors, while the S2 subunit mediates fusion between the virus and the cell membrane. , S protein is an abundant viral transmembrane protein, and the amino acid sequence of this glycoprotein is different from other coronaviruses, so S protein is a suitable target protein for selective recognition of SARS-CoV-2.…”