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  1. Article ; Online: Orthogonal immunoassays for IgG antibodies to SARS-CoV-2 antigens reveal that immune response lasts beyond 4 mo post illness onset.

    Sasisekharan, Varun / Pentakota, Niharika / Jayaraman, Akila / Tharakaraman, Kannan / Wogan, Gerald N / Narayanasami, Uma

    Proceedings of the National Academy of Sciences of the United States of America

    2020  Volume 118, Issue 5

    Abstract: Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the current pandemic remains a field of immense interest and active research worldwide. Although the severity of acute infection may depend on the intensity ... ...

    Abstract Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the current pandemic remains a field of immense interest and active research worldwide. Although the severity of acute infection may depend on the intensity of innate and adaptive immunity, leading to higher morbidity and mortality, the longevity of IgG antibodies, including neutralizing activity to SARS-CoV-2, is viewed as a key correlate of immune protection. Amid reports and concern that there is a rapid decay of IgG antibody levels within 1 mo to 2 mo after acute infection, we set out to study the pattern and duration of IgG antibody response to various SARS-CoV-2 antigens in asymptomatic and symptomatic patients in a community setting. Herein, we show the correlation of IgG anti-spike protein S1 subunit, receptor binding domain, nucleocapsid, and virus neutralizing antibody titers with each other and with clinical features such as length and severity of COVID-19 illness. More importantly, using orthogonal measurements, we found the IgG titers to persist for more than 4 mo post symptom onset, implying that long-lasting immunity to COVID-19 from infection or vaccination might be observed, as seen with other coronaviruses such as SARS and Middle East respiratory syndrome.
    MeSH term(s) Adult ; Antibodies, Viral/blood ; COVID-19/immunology ; Female ; Humans ; Immunity, Humoral ; Immunoassay ; Immunoglobulin G/blood ; Longitudinal Studies ; Male ; Middle Aged ; SARS-CoV-2/immunology
    Chemical Substances Antibodies, Viral ; Immunoglobulin G
    Language English
    Publishing date 2020-12-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2021615118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Prediction of the binding interface between monoclonal antibody m102.4 and Nipah attachment glycoprotein using structure-guided alanine scanning and computational docking.

    Tit-Oon, Phanthakarn / Tharakaraman, Kannan / Artpradit, Charlermchai / Godavarthi, Abhinav / Sungkeeree, Pareenart / Sasisekharan, Varun / Kerdwong, Jarunee / Miller, Nathaniel Loren / Mahajan, Bhuvna / Khongmanee, Amnart / Ruchirawat, Mathuros / Sasisekharan, Ram / Fuangthong, Mayuree

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 18256

    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 ... ...

    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.
    MeSH term(s) Alanine/chemistry ; Alanine/genetics ; Animals ; Antibodies, Monoclonal/chemistry ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/metabolism ; Antibodies, Neutralizing/chemistry ; Antibodies, Neutralizing/immunology ; Antibodies, Neutralizing/metabolism ; Antigen-Antibody Complex/chemistry ; Antigen-Antibody Complex/immunology ; Antigen-Antibody Complex/metabolism ; Computer Simulation ; Epitopes/immunology ; Glycoproteins/chemistry ; Glycoproteins/genetics ; Glycoproteins/metabolism ; Henipavirus Infections/immunology ; Henipavirus Infections/metabolism ; Henipavirus Infections/virology ; Humans ; Mutagenesis, Site-Directed ; Nipah Virus/immunology ; Nipah Virus/isolation & purification ; Nipah Virus/metabolism ; Protein Structural Elements/immunology ; Viral Envelope Proteins/chemistry ; Viral Envelope Proteins/genetics ; Viral Envelope Proteins/metabolism
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antigen-Antibody Complex ; Epitopes ; Glycoproteins ; Viral Envelope Proteins ; Alanine (OF5P57N2ZX)
    Language English
    Publishing date 2020-10-26
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-75056-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Prediction of the binding interface between monoclonal antibody m102.4 and Nipah attachment glycoprotein using structure-guided alanine scanning and computational docking

    Phanthakarn Tit-oon / Kannan Tharakaraman / Charlermchai Artpradit / Abhinav Godavarthi / Pareenart Sungkeeree / Varun Sasisekharan / Jarunee Kerdwong / Nathaniel Loren Miller / Bhuvna Mahajan / Amnart Khongmanee / Mathuros Ruchirawat / Ram Sasisekharan / Mayuree Fuangthong

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 11

    Abstract: 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 ... ...

    Abstract 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.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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