Programme

P.20 -- Poster, VCTP-47

Date: Tuesday, 2 August 2022

Time: 08:30 - 10:00

Grafting Methionine on 1F1 Antibody Increases the Broad-Activity on HA Structural-Conserved Residues of H1, H2, and H3 Influenza A Viruses

Hoa Thanh Le (1,2,3), Phuc-Chau Do (3), Ly Le (3,4)

(1) Laboratory of Theoretical and Computational Biophysics, Advanced Institute of Materials Science, Ton Duc Thang University, Ho Chi Minh City, Vietnam; (2) Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam; (3) School of Biotechnology, International University, Vietnam National University, Ho Chi Minh City, Vietnam; (4) Vingroup Big Data Institute, Hanoi, Vietnam

A high level of mutation enables the influenza A virus (IAV) to resist antibiotics treatment. A portion of the structure of hemagglutinin (HA), a protein of IAV responsible for cellular entry is assumed to be well-conserved to maintain its role, while the structure tends to be more conserved than sequence. We aimed to increase the breadth of activity of the complementarity-determining regions (CDR) of antibodies known to target H1 subtype of IAV so that the CDR can target H2 and H3 subtypes as well. The design entailed grafting onto the CDR with a hotspot amino acid that formed favorable contact with the conserved residues on the HA surface identified based on structural alignment. The contact was evaluated using molecular docking, a method employing empirical functions to calculate the change of free energy upon molecular binding. Methionine amino acid was scored best when it is interacting with Tyrosine, Arginine, and Glutamic acid on HA. The methionine-grafted CDR fragment were found to be to form in silico contact with a structurally conserved region across H1, H2, and H3 HA. The binding site lies at the boundary between HA1 and HA2 domains, spreading across different monomers, suggesting a new target for designing broad-spectrum antibody and vaccine. This research presents an affordable method to enhance the spectrum of CDR from known antibodies based on hotspot grafting assisted by molecular docking.

Presenter: Lê Thanh Hòa