Molecular Docking of Broad-Spectrum Antibodies on Hemagglutinins of Influenza A Virus

Abstract

Influenza A has caused several deadly pandemics throughout human history. The virus is often resistant to developed treatments because of its genetic drift or shift property. Broad-spectrum antibodies show a promising potential to overcome the resistance of influenza viruses. In silico studies on broad-reactive antibodies and their interactions with hemagglutinins might shed light on the rational design of a universal vaccine. In this study, 11 broad-spectrum antibodies (or antigen-binding fragments) and 14 hemagglutinins of H3N2 and H5N1 strains were docked and analyzed to provide information about the construction of the scaffold for using universal antibodies against the influenza A virus. Antigen-binding fragments that have high number of appearances in the top 3 within each H3 and H5 subtypes were chosen for protein-protein interaction analysis. The results show that while the hydrogen bond is important for Ab/Fab binding to H3, the H5-Ab/Fab system may need cation-pi interaction for a strong interaction.

Repurposing of Drugs Against Mutated Strain of Eurasian Avian Like H1N1 (EA H1N1) Swine Flu Virus, Genotype 4(G4) Virus

“…HA protein was chosen as a drug target due to its role in binding of virus to the upper respiratory tract of human, mediating viral entry and fusion(Le et al, 2019).…”

“…HA protein was chosen as a drug target due to its role in binding of virus to the upper respiratory tract of human, mediating viral entry and fusion (Le et al, 2019). Polymerase Acidic (PA) protein was selected as target protein as it is RNA dependent RNA polymerase with several roles such as endonuclease function, protease activity and viral RNA/ complementary RNA promoter binding (Yuan et al 2009).…”

“…The swine viruses possess ability to bind sialic acid in both α-2,3 and α-2,6 linkages (Gamblin & Skehel, 2010) having properties of avian/equine influenza viruses that preferentially binds to the sialic acid in α-2,3-linkage to galactose (Ito et al 1998)and human influenza virus that preferentially bound to α-2,6-linked sialic acid (Ito et al 1998). The initial process of infection occurs when the globular head of the HA binds to the sialic acid receptors present on the host membrane and virion and the lower pH facilitates the cleavage of the cylindrical tail from the globular head for host endosome membrane and viral membrane to fuses together releasing viral RNA and protein into the cytoplasm of the host (K. P. Le et al, 2019;Russell et al, 2018) to internalize through endocytosis. Thus, G4 EAH1N1 influenza virus protein, HA is a good target for treatment and prevention of transmission.…”

Molecular Modeling of Viral Type I Fusion Proteins: Inhibitors of Influenza Virus Hemagglutinin and the Spike Protein of Coronavirus

“…Despite the fact that the first role of HA entails its binding to a cell receptor, the region close to RBS is also attractive for studying the interaction of antibodies with HA 1 , in particular, of influenza viruses of different strains. Thus, in [35] the methods in silico estimated the affinity of a number of antibodies to potential binding sites in the globular domain of HA. Similar studies [36] are of greater interest from the perspective of the rational design of a universal vaccine.…”

Broad-Spectrum Activity of Small Molecules Acting against Influenza a Virus: Biological and Computational Studies

“…A comprehensive computational study has been carried out using both docking and molecular dynamics (MD) calculations to better depict the interaction between these molecules and target HAs, providing a suggestion regarding their mechanism of action. Structure-based approaches are often applied to study the binding of proteins, peptides, and small molecules interacting with HA [ 42 , 43 , 44 , 45 , 46 ]. The schema of the different phases of the work is summarized in Figure 2 .…”