scholarly journals Prediction of the binding interface between monoclonal antibody m102.4 and Nipah attachment glycoprotein using structure-guided alanine scanning and computational docking

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Phanthakarn Tit-oon ◽  
Kannan Tharakaraman ◽  
Charlermchai Artpradit ◽  
Abhinav Godavarthi ◽  
Pareenart Sungkeeree ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Structural Model ◽  
Affinity Maturation ◽  
Hendra Virus ◽  
World Health ◽  
Alanine Scanning Mutagenesis ◽  
Alanine Scanning ◽  
Computational Docking ◽  
Binding Interface ◽  
Starting Point

Abstract Nipah Virus (NiV) has been designated as a priority disease with an urgent need for therapeutic development by World Health Organization. The monoclonal antibody m102.4 binds to the immunodominant NiV receptor-binding glycoprotein (GP), and potently neutralizes NiV, indicating its potential as a therapeutic agent. Although the co-crystal structure of m102.3, an m102.4 derivative, in complex with the GP of the related Hendra Virus (HeV) has been solved, the structural interaction between m102.4 and NiV is uncharacterized. Herein, we used structure-guided alanine-scanning mutagenesis to map the functional epitope and paratope residues that govern the antigen–antibody interaction. Our results revealed that the binding of m102.4 is mediated predominantly by two residues in the HCDR3 region, which is unusually small for an antibody-antigen interaction. We performed computational docking to generate a structural model of m102.4-NiV interaction. Our model indicates that m102.4 targets the common hydrophobic central cavity and a hydrophilic rim on the GP, as observed for the m102.3-HeV co-crystal, albeit with Fv orientation differences. In summary, our study provides insight into the m102.4-NiV interaction, demonstrating that structure-guided alanine-scanning and computational modeling can serve as the starting point for additional antibody reengineering (e.g. affinity maturation) to generate potential therapeutic candidates.

scholarly journals The anti-Mullerian hormone type II receptor: insights into the binding domains recognized by a monoclonal antibody and the natural ligand

2004 ◽  
Vol 379 (3) ◽  
pp. 785-793 ◽  
Author(s):  
Imed SALHI ◽  
Sylvie CAMBON-ROQUES ◽  
Isabelle LAMARRE ◽  
Daniel LAUNE ◽  
Franck MOLINA ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Structural Model ◽  
Transforming Growth Factor ◽  
Chinese Hamster ◽  
Transforming Growth Factor Β ◽  
Cross Reactivity ◽  
Ovary Cell ◽  
Type Ii ◽  
Male Embryo ◽  
Binding Interface

Anti-Müllerian hormone (AMH) [also called Müllerian inhibiting substance (MIS)] is a member of the transforming growth factor-β family. AMH and its type II receptor (AMHR-II) are involved in the regression of the Müllerian ducts in the male embryo, and in gonadal functions in the adult. AMH is also known to be a marker of granulosa and Sertoli cell tumours. We selected a high-affinity monoclonal antibody, mAb 12G4, specific for human AMHR-II (hAMHR-II), by FACS analysis, Western blotting and immunohistochemical staining of a hAMHR-II-transfected CHO (Chinese hamster ovary) cell line, normal adult testicular tissue and granulosa cell tumours. Using peptide array screening, we identified the binding sequences of mAb 12G4 and AMH on the receptor. Identification of Asp53 and Ala55 as critical residues in the DRAQVEM minimal epitopic sequence of mAb 12G4 definitively accounted for the lack of cross-reactivity with the murine receptor, in which there is a glycine residue in place of an aspartic acid residue. In a structural model, the AMH-binding interface was mapped to the concave side of hAMHR-II, whereas the mAb 12G4-binding site was located on the convex side. mAb 12G4, the first mAb to be raised against hAMHR-II, therefore has unique properties that could make it a valuable tool for the immunotargeting of tumours expressing this receptor.

scholarly journals Analysis of Hendra Virus Fusion Protein N-Terminal Transmembrane Residues

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2353
Author(s):  
Chelsea T. Barrett ◽  
Hadley E. Neal ◽  
Kearstin Edmonds ◽  
J. Lizbeth Reyes Zamora ◽  
Carole L. Moncman ◽  
...  
Keyword(s):  
Host Cell ◽  
Protein Function ◽  
Hendra Virus ◽  
Proteolytic Processing ◽  
Viral Envelope ◽  
Alanine Scanning Mutagenesis ◽  
Alanine Scanning ◽  
F Protein ◽  
The Family ◽  
N Terminus

Hendra virus (HeV) is a zoonotic enveloped member of the family Paramyoxviridae. To successfully infect a host cell, HeV utilizes two surface glycoproteins: the attachment (G) protein to bind, and the trimeric fusion (F) protein to merge the viral envelope with the membrane of the host cell. The transmembrane (TM) region of HeV F has been shown to have roles in F protein stability and the overall trimeric association of F. Previously, alanine scanning mutagenesis has been performed on the C-terminal end of the protein, revealing the importance of β-branched residues in this region. Additionally, residues S490 and Y498 have been demonstrated to be important for F protein endocytosis, needed for the proteolytic processing of F required for fusion. To complete the analysis of the HeV F TM, we performed alanine scanning mutagenesis to explore the residues in the N-terminus of this region (residues 487–506). In addition to confirming the critical roles for S490 and Y498, we demonstrate that mutations at residues M491 and L492 alter F protein function, suggesting a role for these residues in the fusion process.

scholarly journals Comprehensive Alanine-scanning Mutagenesis of Escherichia coli CsrA Defines Two Subdomains of Critical Functional Importance

2006 ◽  
Vol 281 (42) ◽  
pp. 31832-31842
Author(s):  
Jeffrey Mercante ◽  
Kazushi Suzuki ◽  
Xiaodong Cheng ◽  
Paul Babitzke ◽  
Tony Romeo
Keyword(s):  
Escherichia Coli ◽  
Functional Importance ◽  
Alanine Scanning Mutagenesis ◽  
Alanine Scanning

scholarly journals Mapping of an NH-terminal Ligand Binding Site of the Insulin Receptor by Alanine Scanning Mutagenesis

1995 ◽  
Vol 270 (7) ◽  
pp. 3012-3016 ◽  
Author(s):  
Paul F. Williams ◽  
Dennis C. Mynarcik ◽  
Gui Qin Yu ◽  
Jonathan Whittaker
Keyword(s):  
Ligand Binding ◽  
Insulin Receptor ◽  
Binding Site ◽  
Ligand Binding Site ◽  
Alanine Scanning Mutagenesis ◽  
Alanine Scanning ◽  
Terminal Ligand

scholarly journals Aspiration in injections: should we continue or abandon the practice?

F1000Research ◽  
2017 ◽  
Vol 3 ◽  
pp. 157
Author(s):  
Yasir Sepah ◽  
Lubna Samad ◽  
Arshad Altaf ◽  
Muhammad Sohail Halim ◽  
Nithya Rajagopalan ◽  
...  
Keyword(s):  
Medical Association ◽  
Simple Procedure ◽  
Health Agency ◽  
Monitoring Network ◽  
Nursing Schools ◽  
Global Network ◽  
World Health ◽  
Sources Of Information ◽  
Starting Point ◽  
The Us

Aspiration during any kind of injection is meant to ensure that the needle tip is at the desired location during this blind procedure. While aspiration appears to be a simple procedure, it has generated a lot of controversy concerning the perceived benefits and indications. Advocates and opponents of aspiration both make logically sound claims. However, due to scarcity of available data, there is no evidence that this procedure is truly beneficial or unwarranted. Keeping in view the huge number of injections given worldwide, it is important that we draw attention to key questions regarding aspiration that, up till now, remain unanswered. In this review, we have attempted to gather and present literature on aspiration both from published and non-published sources in order to provide not only an exhaustive review of the subject, but also a starting point for further studies on more specific areas requiring clarification. A literature review was conducted using the US National Institute of Health’s PubMed service (including Medline), Google Scholar and Scopus. Guidelines provided by the World Health Organization, Safe Injection Global Network, International Council of Nursing, Center for Disease Control, US Federal Drug Agency, UK National Health Services, British Medical Association, Europe Nursing and Midwifery Council, Public Health Agency Canada, Pakistan Medical Association and International Organization of Standardization recommendations 7886 parts 1-4 for sterile hypodermics were reviewed for relevant information. In addition, curricula of several medical/nursing schools from India, Nigeria and Pakistan, the US pharmacopeia Data from the WHO Program for International Drug Monitoring network in regard to adverse events as a result of not aspirating prior to injection delivery were reviewed. Curricula of selected major medical/nursing schools in India, Nigeria and Pakistan, national therapeutic formularies, product inserts of most commonly used drugs and other possible sources of information regarding aspiration and injections were consulted as well.

scholarly journals Managing Borders During Public Health Emergencies of International Concern: A Proposed Typology of Cross-border Health Measures

2021 ◽  
Author(s):  
Kelley Lee ◽  
Karen A Grépin ◽  
Catherine Worsnop ◽  
Summer Marion ◽  
Julianne Piper ◽  
...  
Keyword(s):  
Public Health ◽  
Research Policy ◽  
Grey Literature ◽  
World Health ◽  
Border Health ◽  
Policy And Practice ◽  
Public Health Emergencies ◽  
Cross Border ◽  
Health Measures ◽  
Starting Point

Abstract BackgroundThe near universal adoption of cross-border health measures during the COVID-19 pandemic worldwide has prompted significant debate about their effectiveness and compliance with international law. The number of measures used, and the range of measures applied, have far exceeded previous public health emergencies of international concern. However, efforts to advance research, policy and practice to support their effective use has been hindered by a lack of clear and consistent definition. ResultsBased on a review of existing datasets for cross-border health measures, such as the Oxford Coronavirus Government Response Tracker and World Health Organization Public Health and Social Measures, along with analysis of secondary and grey literature, we propose six categories to define measures more clearly and consistently – type of movement (travel and trade), policy goal, level of jurisdiction, use by public versus private sector, stage of journey, and degree of restrictiveness. These categories are then be brought together into a proposed typology that can support research with generalizable findings and comparative analyses across jurisdictions. The typology facilitates evidence-informed decision-making which takes account of policy complexity including trade-offs and externalities. Finally, the typology can support efforts to strengthen coordinated global responses to outbreaks and inform future efforts to revise the WHO International Health Regulations (2005). ConclusionsThe widespread use of cross-border health measures during the COVID-19 pandemic has prompted significant reflection on available evidence, previous practice and existing legal frameworks. The typology put forth in this paper aims to provide a starting point for strengthening research, policy and practice.

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