tetano
Editor, Senior Moderator
Comput Biol Chem
. 2024 Aug 27:113:108189.
doi: 10.1016/j.compbiolchem.2024.108189. Online ahead of print. Theoretical Investigations of a point mutation affecting H5 Hemagglutinin's receptor binding preference
Quoc Bao Ngo[SUP] 1 [/SUP], André H Juffer[SUP] 2 [/SUP]
Affiliations
The avian influenza A H5N1 virus is a subtype of influenza A virus (IAV) that causes a highly infectious and severe respiratory illness in birds and poses significant economic losses in poultry farming. To infect host cell, the virus uses its surface glycoprotein named Hemagglutinin (HA) to recognize and to interact with the host cell receptor containing either α2,6- (SAα2,6 Gal) or α2,3-linked Sialic Acid (SAα2,3 Gal). The H5N1 virus has not yet acquired the capability for efficient human-to-human transmission. However, studies have demonstrated that even a single amino acid substitution in the HA can switch its glycan receptor preference from the avian-type SAα2,3 Gal to the human-type SAα2,6 Gal. The present study aims to explain the underlying mechanism of a mutation (D94N) on the H5 HA that causes the protein to change its glycan receptor-binding preference using molecular dynamics (MD) simulations. Our results reveal that the mutation alters the electrostatic interactions pattern near the HA receptor binding pocket, leading to a reduced stability for the HA-avian-type SAα2,3 Gal complex. On the other hand, the detrimental effect of the mutation D94N is not observed in the HA-human-type SAα2,6 Gal complex due to the glycan's capability to switch its topology.
Keywords: Hemagglutinin; Influenza A virus; Molecular dynamics; Mutation; Sialic acid.
. 2024 Aug 27:113:108189.
doi: 10.1016/j.compbiolchem.2024.108189. Online ahead of print. Theoretical Investigations of a point mutation affecting H5 Hemagglutinin's receptor binding preference
Quoc Bao Ngo[SUP] 1 [/SUP], André H Juffer[SUP] 2 [/SUP]
Affiliations
- PMID: 39216409
- DOI: 10.1016/j.compbiolchem.2024.108189
The avian influenza A H5N1 virus is a subtype of influenza A virus (IAV) that causes a highly infectious and severe respiratory illness in birds and poses significant economic losses in poultry farming. To infect host cell, the virus uses its surface glycoprotein named Hemagglutinin (HA) to recognize and to interact with the host cell receptor containing either α2,6- (SAα2,6 Gal) or α2,3-linked Sialic Acid (SAα2,3 Gal). The H5N1 virus has not yet acquired the capability for efficient human-to-human transmission. However, studies have demonstrated that even a single amino acid substitution in the HA can switch its glycan receptor preference from the avian-type SAα2,3 Gal to the human-type SAα2,6 Gal. The present study aims to explain the underlying mechanism of a mutation (D94N) on the H5 HA that causes the protein to change its glycan receptor-binding preference using molecular dynamics (MD) simulations. Our results reveal that the mutation alters the electrostatic interactions pattern near the HA receptor binding pocket, leading to a reduced stability for the HA-avian-type SAα2,3 Gal complex. On the other hand, the detrimental effect of the mutation D94N is not observed in the HA-human-type SAα2,6 Gal complex due to the glycan's capability to switch its topology.
Keywords: Hemagglutinin; Influenza A virus; Molecular dynamics; Mutation; Sialic acid.