Affinity Improvement of a Humanized Antiviral Antibody by Structure-Based Computational Design

  • Tayebeh Farhadi
  • Atefeh Fakharian
  • Seyed MohammadReza HashemianEmail author


Acquired immune deficiency syndrome (AIDS) is one of the most lethal infectious diseases influencing human community. While fusion of HIV-1 and host cell membranes, viral envelope glycoprotein gp120 is dissociated and a cascade of refolding events is initiated in the viral fusion protein gp41. To promote formation of the co-receptor binding site on the gp120 and initial attachment, HIV-1 employs CD4 as its primary receptor. Ibalizumab, a humanized, anti-CD4 monoclonal antibody for HIV-1 infection, was investigated in silico to design a potential improved antibody. Computer-aided antibody engineering has been successful in the design of new biologics for disease diagnosis and therapeutic interventions. Here, crystal structure of CD4 along with monoclonal antibody Ibalizumab was explored. Thr30, Ser31, Asn52, Tyr53, Asn98 and Tyr99 in heavy chain of Ibalizumab were mutated with 19 standard amino acid residues using computational methods. A set of 720 mutant macromolecules were designed, and binding affinity of these macromolecules to CD4 was evaluated through Ag-Ab docking, binding free-energy calculations, and hydrogen binding estimation. In comparison to Ibalizumab, seven designed theoretical antibody demonstrated better result in all assessments. Therefore, these newly designed macromolecules were proposed as potential antibodies to serve as therapeutic options for HIV infection.


Computer-aided antibody engineering Affinity improvement Ibalizumab 


Compliance with Ethical Standards

Conflict of interest

Tayebeh Farhadi, Atefeh Fakharian and Seyed MohammadReza Hashemian declare that they have no conflict of interest.

Research involving with Human and Animal Rights

This article does not contain any studies with human or animal subject performed by the author.

Supplementary material

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Supplementary material 1 (DOCX 2252 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Tayebeh Farhadi
    • 1
  • Atefeh Fakharian
    • 1
  • Seyed MohammadReza Hashemian
    • 1
    Email author
  1. 1.Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran

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