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Development of multivalent nanobodies blocking SARS-CoV-2 infection by targeting RBD of spike protein.
Lu, Qizhong; Zhang, Zongliang; Li, Hexian; Zhong, Kunhong; Zhao, Qin; Wang, Zeng; Wu, Zhiguo; Yang, Donghui; Sun, Shuang; Yang, Nian; Zheng, Meijun; Chen, Qiang; Long, Cheng; Guo, Wenhao; Yang, Hui; Nie, Chunlai; Tong, Aiping.
  • Lu Q; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Zhang Z; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Li H; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Zhong K; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Zhao Q; Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China.
  • Wang Z; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Wu Z; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Yang D; College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, 712100, China.
  • Sun S; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Yang N; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Zheng M; Department of Otolaryngology, Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Chen Q; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Long C; Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Guo W; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Yang H; Department of Otolaryngology, Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Nie C; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China. niecl1022@scu.edu.cn.
  • Tong A; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China. aipingtong@scu.edu.cn.
J Nanobiotechnology ; 19(1): 33, 2021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1054825
Semantic information from SemMedBD (by NLM)
1. VHH Immunoglobulin Fragments AFFECTS COVID-19
Subject
VHH Immunoglobulin Fragments
Predicate
AFFECTS
Object
COVID-19
2. RNA Recognition Motif PART_OF M Protei
Subject
RNA Recognition Motif
Predicate
PART_OF
Object
M Protei
3. Virus LOCATION_OF VHH Immunoglobulin Fragments
Subject
Virus
Predicate
LOCATION_OF
Object
VHH Immunoglobulin Fragments
4. Single-Chain Antibodies CONVERTS_TO VHH Immunoglobulin Fragments
Subject
Single-Chain Antibodies
Predicate
CONVERTS_TO
Object
VHH Immunoglobulin Fragments
5. VHH Immunoglobulin Fragments AFFECTS COVID-19
Subject
VHH Immunoglobulin Fragments
Predicate
AFFECTS
Object
COVID-19
6. RNA Recognition Motif PART_OF M Protein, multiple myeloma
Subject
RNA Recognition Motif
Predicate
PART_OF
Object
M Protein, multiple myeloma
7. Virus LOCATION_OF VHH Immunoglobulin Fragments
Subject
Virus
Predicate
LOCATION_OF
Object
VHH Immunoglobulin Fragments
8. Single-Chain Antibodies CONVERTS_TO VHH Immunoglobulin Fragments
Subject
Single-Chain Antibodies
Predicate
CONVERTS_TO
Object
VHH Immunoglobulin Fragments
ABSTRACT

BACKGROUND:

The 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 single­chain 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.

RESULTS:

Totally, 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 IC50 value at approximately 1.54 nM.

CONCLUSIONS:

The 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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Single-Domain Antibodies / Spike Glycoprotein, Coronavirus Limits: Humans Language: English Journal: J Nanobiotechnology Year: 2021 Document Type: Article Affiliation country: S12951-021-00768-w

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Single-Domain Antibodies / Spike Glycoprotein, Coronavirus Limits: Humans Language: English Journal: J Nanobiotechnology Year: 2021 Document Type: Article Affiliation country: S12951-021-00768-w