Development of multivalent nanobodies blocking SARS-CoV-2 infection by targeting RBD of spike protein

التفاصيل البيبلوغرافية
العنوان: Development of multivalent nanobodies blocking SARS-CoV-2 infection by targeting RBD of spike protein
المؤلفون: Aiping Tong, Cheng Long, Shuang Sun, Qiang Chen, Donghui Yang, Meijun Zheng, Zongliang Zhang, Hui Yang, Qin Zhao, Chunlai Nie, Zhiguo Wu, Nian Yang, Hexian Li, Wenhao Guo, Zeng Wang, Kunhong Zhong, Qizhong Lu
المصدر: Journal of Nanobiotechnology
Journal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-12 (2021)
بيانات النشر: BioMed Central, 2021.
سنة النشر: 2021
مصطلحات موضوعية: lcsh:Medical technology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lcsh:Biotechnology, Protein domain, Biomedical Engineering, Pharmaceutical Science, Medicine (miscellaneous), Bioengineering, Spike, Plasma protein binding, medicine.disease_cause, Antibodies, Viral, Applied Microbiology and Biotechnology, RBD, 03 medical and health sciences, 0302 clinical medicine, Protein Domains, Neutralization Tests, lcsh:TP248.13-248.65, medicine, Humans, Binding site, 030304 developmental biology, Coronavirus, 0303 health sciences, Binding Sites, biology, SARS-CoV-2, Research, HEK 293 cells, Spike Protein, Single-Domain Antibodies, Virology, Antibodies, Neutralizing, HEK293 Cells, lcsh:R855-855.5, 030220 oncology & carcinogenesis, Spike Glycoprotein, Coronavirus, biology.protein, Nanobody, Molecular Medicine, Antibody, Pseudovirus neutralization, Protein Binding
الوصف: BackgroundThe outbreak and pandemic of coronavirus SARS-CoV-2 caused significant threaten to global public health and economic consequences. It is extremely urgent that global people must take actions to develop safe and effective preventions and therapeutics. Nanobodies, which are derived from single‑chain camelid antibodies, had shown antiviral properties in various challenge viruses. In this study, multivalent nanobodies with high affinity blocking SARS-CoV-2 spike interaction with ACE2 protein were developed.ResultsTotally, four specific nanobodies against spike protein and its RBD domain were screened from a naïve VHH library. Among them, Nb91-hFc and Nb3-hFc demonstrated antiviral activity by neutralizing spike pseudotyped viruses in vitro. Subsequently, multivalent nanobodies were constructed to improve the neutralizing capacity. As a result, heterodimer nanobody Nb91-Nb3-hFc exhibited the strongest RBD-binding affinity and neutralizing ability against SARS-CoV-2 pseudoviruses with an IC50value at approximately 1.54 nM.ConclusionsThe present study indicated that naïve VHH library could be used as a potential resource for rapid acquisition and exploitation of antiviral nanobodies. Heterodimer nanobody Nb91-Nb3-hFc may serve as a potential therapeutic agent for the treatment of COVID-19.
اللغة: English
تدمد: 1477-3155
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0497190dcad17a44f4c3f573d54455e3
http://europepmc.org/articles/PMC7844813
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....0497190dcad17a44f4c3f573d54455e3
قاعدة البيانات: OpenAIRE