tetano
Editor, Senior Moderator
ACS Nano
. 2023 Mar 27.
doi: 10.1021/acsnano.3c02050. Online ahead of print.
Abiotic Synthetic Antibody Inhibitor with Broad-Spectrum Neutralization and Antiviral Efficacy against Escaping SARS-CoV-2 Variants
Bingxue Li[SUP] 1 [/SUP], Ya Zhao[SUP] 2 [/SUP], Xuefan Wu[SUP] 3 4 [/SUP], Haiyan Wu[SUP] 1 [/SUP], Weicheng Tang[SUP] 1 [/SUP], Xiaoyang Yu[SUP] 1 [/SUP], Jianqiong Mou[SUP] 1 [/SUP], Wenfeng Tan[SUP] 1 [/SUP], Meilin Jin[SUP] 2 5 6 [/SUP], Wei Li[SUP] 7 [/SUP], Qiang Zhang[SUP] 2 5 8 [/SUP], Mingming Liu[SUP] 1 [/SUP]
Affiliations
Abstract
The rapid emergence and spread of vaccine/antibody-escaping variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious challenges to our efforts in combating corona virus disease 2019 (COVID-19) pandemic. A potent and broad-spectrum neutralizing reagent against these escaping mutants is extremely important for the development of strategies for the prevention and treatment of SARS-CoV-2 infection. We herein report an abiotic synthetic antibody inhibitor as a potential anti-SARS-CoV-2 therapeutic agent. The inhibitor, Aphe-NP14, was selected from a synthetic hydrogel polymer nanoparticle library created by incorporating monomers with functionalities complementary to key residues of the SARS-CoV-2 spike glycoprotein receptor binding domain (RBD) involved in human angiotensin-converting enzyme 2 (ACE2) binding. It has high capacity, fast adsorption kinetics, strong affinity, and broad specificity in biologically relevant conditions to both the wild type and the current variants of concern, including Beta, Delta, and Omicron spike RBD. The Aphe-NP14 uptake of spike RBD results in strong blockage of spike RBD-ACE2 interaction and thus potent neutralization efficacy against these escaping spike protein variant pseudotyped viruses. It also inhibits live SARS-CoV-2 virus recognition, entry, replication, and infection in vitro and in vivo. The Aphe-NP14 intranasal administration is found to be safe due to its low in vitro and in vivo toxicity. These results establish a potential application of abiotic synthetic antibody inhibitors in the prevention and treatment of the infection of emerging or possibly future SARS-CoV-2 variants.
Keywords: SARS-CoV-2; abiotic synthetic antibody; escaping variants; hydrogel polymer nanoparticle; spike RBD; therapeutic inhibitor.
. 2023 Mar 27.
doi: 10.1021/acsnano.3c02050. Online ahead of print.
Abiotic Synthetic Antibody Inhibitor with Broad-Spectrum Neutralization and Antiviral Efficacy against Escaping SARS-CoV-2 Variants
Bingxue Li[SUP] 1 [/SUP], Ya Zhao[SUP] 2 [/SUP], Xuefan Wu[SUP] 3 4 [/SUP], Haiyan Wu[SUP] 1 [/SUP], Weicheng Tang[SUP] 1 [/SUP], Xiaoyang Yu[SUP] 1 [/SUP], Jianqiong Mou[SUP] 1 [/SUP], Wenfeng Tan[SUP] 1 [/SUP], Meilin Jin[SUP] 2 5 6 [/SUP], Wei Li[SUP] 7 [/SUP], Qiang Zhang[SUP] 2 5 8 [/SUP], Mingming Liu[SUP] 1 [/SUP]
Affiliations
- PMID: 36971310
- DOI: 10.1021/acsnano.3c02050
Abstract
The rapid emergence and spread of vaccine/antibody-escaping variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious challenges to our efforts in combating corona virus disease 2019 (COVID-19) pandemic. A potent and broad-spectrum neutralizing reagent against these escaping mutants is extremely important for the development of strategies for the prevention and treatment of SARS-CoV-2 infection. We herein report an abiotic synthetic antibody inhibitor as a potential anti-SARS-CoV-2 therapeutic agent. The inhibitor, Aphe-NP14, was selected from a synthetic hydrogel polymer nanoparticle library created by incorporating monomers with functionalities complementary to key residues of the SARS-CoV-2 spike glycoprotein receptor binding domain (RBD) involved in human angiotensin-converting enzyme 2 (ACE2) binding. It has high capacity, fast adsorption kinetics, strong affinity, and broad specificity in biologically relevant conditions to both the wild type and the current variants of concern, including Beta, Delta, and Omicron spike RBD. The Aphe-NP14 uptake of spike RBD results in strong blockage of spike RBD-ACE2 interaction and thus potent neutralization efficacy against these escaping spike protein variant pseudotyped viruses. It also inhibits live SARS-CoV-2 virus recognition, entry, replication, and infection in vitro and in vivo. The Aphe-NP14 intranasal administration is found to be safe due to its low in vitro and in vivo toxicity. These results establish a potential application of abiotic synthetic antibody inhibitors in the prevention and treatment of the infection of emerging or possibly future SARS-CoV-2 variants.
Keywords: SARS-CoV-2; abiotic synthetic antibody; escaping variants; hydrogel polymer nanoparticle; spike RBD; therapeutic inhibitor.