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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315882

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 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. 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.

2.
J Nanobiotechnology ; 19(1): 33, 2021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1054825

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)
Single-Domain Antibodies/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Binding Sites , HEK293 Cells , Humans , Neutralization Tests , Protein Binding , Protein Domains , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/antagonists & inhibitors
3.
Front Neurol ; 11: 659, 2020.
Article in English | MEDLINE | ID: covidwho-634494

ABSTRACT

SARS-CoV-2 is a novel coronavirus leading to serious respiratory disease and is spreading around the world at a raging speed. Recently there is emerging speculations that the central nervous system (CNS) may be involved during SARS-CoV-2 infection, contributing to the respiratory failure. However, the existence of viral replication in CNS has not been confirmed due to the lack of evidence from autopsy specimens. Considering the tropism of SARS-CoV-2, ACE2, is prevailing in CNS, and the neuro-invasive property of human coronavirus was widely reported, there is a need to identified the possible complications during COVID-19 for CNS. In this review, we conduct a detailed summary for the potential of SARS-CoV-2 to infect central nervous system from latest biological fundamental of SARS-CoV-2 to the clinical experience of other human coronaviruses. To confirm the neuro-invasive property of SARS-CoV-2 and the subsequent influence on patients will require further exploration by both virologist and neurologist.

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