scholarly journals Isolation and Characterization of Human Monoclonal Antibodies That Recognize the Influenza A(H1N1)pdm09 Virus Hemagglutinin Receptor-Binding Site and Rarely Yield Escape Mutant Viruses

2018 ◽  
Vol 9 ◽  
Author(s):  
Atsuhiro Yasuhara ◽  
Seiya Yamayoshi ◽  
Mutsumi Ito ◽  
Maki Kiso ◽  
Shinya Yamada ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Binding Site ◽  
Receptor Binding ◽  
Influenza A ◽  
Escape Mutant ◽  
Human Monoclonal Antibodies ◽  
Receptor Binding Site ◽  
Isolation And Characterization ◽  
Influenza A H1n1

scholarly journals Characterization of Two Human Monoclonal Antibodies Neutralizing Influenza A H7N9 Viruses

2015 ◽  
Vol 89 (17) ◽  
pp. 9115-9118 ◽  
Author(s):  
Jianmin Wang ◽  
Zhe Chen ◽  
Linlin Bao ◽  
Weijia Zhang ◽  
Ying Xue ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Global Health ◽  
Influenza A ◽  
Severe Infection ◽  
Health Concern ◽  
Phage Library ◽  
Human Monoclonal Antibodies ◽  
Receptor Binding Site ◽  
Antibody Phage

H7N9 was a cause of significant global health concern due to its severe infection and approximately 35% mortality in humans. By screening a Fab antibody phage library derived from patients who recovered from H7N9 infections, we characterized two human monoclonal antibodies (HuMAbs), HNIgGD5 and HNIgGH8. The epitope of these two antibodies was dependent on two residues in the receptor binding site at positions V186 and L226 of the hemagglutinin glycoprotein. Both antibodies possessed high neutralizing activity.

scholarly journals Potent sialic acid inhibitors that target influenza A virus hemagglutinin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu-Jen Chang ◽  
Cheng-Yun Yeh ◽  
Ju-Chien Cheng ◽  
Yu-Qi Huang ◽  
Kai-Cheng Hsu ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Antiviral Activity ◽  
Binding Site ◽  
Influenza A Virus ◽  
Receptor Binding ◽  
Influenza A ◽  
The United States ◽  
Ligand Complex ◽  
Receptor Binding Site ◽  
Computational Strategy

AbstractEradicating influenza A virus (IAV) is difficult, due to its genetic drift and reassortment ability. As the infectious cycle is initiated by the influenza glycoprotein, hemagglutinin (HA), which mediates the binding of virions to terminal sialic acids moieties, HA is a tempting target of anti-influenza inhibitors. However, the complexity of the HA structure has prevented delineation of the structural characterization of the HA protein–ligand complex. Our computational strategy efficiently analyzed > 200,000 records of compounds held in the United States National Cancer Institute (NCI) database and identified potential HA inhibitors, by modeling the sialic acid (SA) receptor binding site (RBS) for the HA structure. Our modeling revealed that compound NSC85561 showed significant antiviral activity against the IAV H1N1 strain with EC50 values ranging from 2.31 to 2.53 µM and negligible cytotoxicity (CC50 > 700 µM). Using the NSC85561 compound as the template to generate 12 derivatives, robust bioassay results revealed the strongest antiviral efficacies with NSC47715 and NSC7223. Virtual screening clearly identified three SA receptor binding site inhibitors that were successfully validated in experimental data. Thus, our computational strategy has identified SA receptor binding site inhibitors against HA that show IAV-associated antiviral activity.

scholarly journals Novel Mutations Evading Avian Immunity around the Receptor Binding Site of the Clade 2.3.2.1c Hemagglutinin Gene Reduce Viral Thermostability and Mammalian Pathogenicity

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 923 ◽  
Author(s):  
An ◽  
Lee ◽  
Hong ◽  
Song ◽  
Kim ◽  
...  
Keyword(s):  
Binding Site ◽  
Receptor Binding ◽  
Mammalian Cells ◽  
Influenza A ◽  
Receptor Binding Site ◽  
Receptor Affinity ◽  
Replication Efficiency ◽  
Adaptive Mutations ◽  
H5n1 Avian Influenza ◽  
Clade 2.3.2.1C

Abstract: Since 2007, highly pathogenic clade 2.3.2 H5N1 avian influenza A (A(H5N1)) viruses have evolved to clade 2.3.2.1a, b, and c; currently only 2.3.2.1c A(H5N1) viruses circulate in wild birds and poultry. During antigenic evolution, clade 2.3.2.1a and c A(H5N1) viruses acquired both S144N and V223I mutations around the receptor binding site of hemagglutinin (HA), with S144N generating an N-glycosylation sequon. We introduced single or combined reverse mutations, N144S and/or I223V, into the HA gene of the clade 2.3.2.1c A(H5N1) virus and generated PR8-derived, 2 + 6 recombinant A(H5N1) viruses. When we compared replication efficiency in embryonated chicken eggs, mammalian cells, and mice, the recombinant virus containing both N144S and I223V mutations showed increased replication efficiency in avian and mammalian hosts and pathogenicity in mice. The N144S mutation significantly decreased avian receptor affinity and egg white inhibition, but not all mutations increased mammalian receptor affinity. Interestingly, the combined reverse mutations dramatically increased the thermostability of HA. Therefore, the adaptive mutations possibly acquired to evade avian immunity may decrease viral thermostability as well as mammalian pathogenicity.

scholarly journals Diversity of antigenic mutants of influenza A(H1N1)pdm09 virus escaped from human monoclonal antibodies

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Atsuhiro Yasuhara ◽  
Seiya Yamayoshi ◽  
Priyanka Soni ◽  
Toru Takenaga ◽  
Chiharu Kawakami ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Influenza A ◽  
Human Monoclonal Antibodies ◽  
Pdm09 Virus ◽  
Influenza A H1n1

scholarly journals Substitutions near the Hemagglutinin Receptor-Binding Site Determine the Antigenic Evolution of Influenza A H3N2 Viruses in U.S. Swine

2014 ◽  
Vol 88 (9) ◽  
pp. 4752-4763 ◽  
Author(s):  
N. S. Lewis ◽  
T. K. Anderson ◽  
P. Kitikoon ◽  
E. Skepner ◽  
D. F. Burke ◽  
...  
Keyword(s):  
Binding Site ◽  
Receptor Binding ◽  
Influenza A ◽  
Receptor Binding Site ◽  
Antigenic Evolution

scholarly journals Monoclonal antibodies targeting the influenza virus N6 neuraminidase

2021 ◽  
Author(s):  
Shirin Strohmeier ◽  
Fatima Amanat ◽  
Juan Manuel Carreño ◽  
Florian Krammer
Keyword(s):  
Monoclonal Antibodies ◽  
Influenza A ◽  
Neutralization Assay ◽  
Escape Mutant ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
Lateral Ridge

AbstractInfluenza A viruses are a diverse species that include 16 hemagglutinin (HA) subtypes and 9 neuraminidase (NA) subtypes. While the antigenicity of many HA subtypes is reasonably well studied, less is known about NA antigenicity, especially when it comes to non-human subtypes that only circulate in animal reservoirs. The N6 NA subtypes are mostly found in viruses infecting birds. However, they have also been identified in viruses that infect mammals, such as swine and seals. More recently, highly pathogenic H5N6 subtype viruses have caused rare infections and mortality in humans. Here, we generated murine mAbs to the N6 NA, characterized their breadth and antiviral properties in vitro and in vivo and mapped their epitopes by generating escape mutant viruses. We found that the antibodies had broad reactivity across the American and Eurasian N6 lineages, but relatively little binding and inhibition of the H5N6 NA. Several of the antibodies exhibited strong NA inhibition activity and some also showed activity in the antibody dependent cellular cytotoxicity reporter assay and neutralization assay. In addition, we generated escape mutant viruses for six monoclonal antibodies and found mutations on the lateral ridge of the NA. Lastly, we observed variable protection in H4N6 and H5N6 mouse challenge models when the antibodies were given prophylactically.ImportanceThe N6 NA has recently gained prominence due to the emergence of highly pathogenic H5N6 viruses. Currently, there is limited characterization of the antigenicity of avian N6 neuraminidase. Our data is an important first step towards a better understanding of the N6 NA antigenicity.

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