tetano
Editor, Senior Moderator
Sci Rep
. 2021 Jul 26;11(1):15162.
doi: 10.1038/s41598-021-94602-w.
S494 O-glycosylation site on the SARS-CoV-2 RBD affects the virus affinity to ACE2 and its infectivity; a molecular dynamics study
Shadi Rahnama[SUP] 1 [/SUP], Maryam Azimzadeh Irani[SUP] 2 [/SUP], Mehriar Amininasab[SUP] 3 [/SUP], Mohammad Reza Ejtehadi[SUP] 4 [/SUP]
Affiliations
Abstract
SARS-CoV-2 is a strain of Coronavirus family that caused the ongoing pandemic of COVID-19. Several studies showed that the glycosylation of virus spike (S) protein and the Angiotensin-Converting Enzyme 2 (ACE2) receptor on the host cell is critical for the virus infectivity. Molecular Dynamics (MD) simulations were used to explore the role of a novel mutated O-glycosylation site (D494S) on the Receptor Binding Domain (RBD) of S protein. This site was suggested as a key mediator of virus-host interaction. By exploring the dynamics of three O-glycosylated models and the control systems of unglcosylated S4944 and S494D complexes, it was shown that the decoration of S494 with elongated O-glycans results in stabilized interactions on the direct RBD-ACE2. Calculation of the distances between RBD and two major H1, H2 helices of ACE2 and the interacting pairs of amino acids in the interface showed that the elongated O-glycan maintains these interactions by forming several polar contacts with the neighbouring residues while it would not interfere in the direct binding interface. Relative binding free energy of RBD-ACE2 is also more favorable in the O-glycosylated models with longer glycans. The increase of RBD binding affinity to ACE2 depends on the size of attached O-glycan. By increasing the size of O-glycan, the RBD-ACE2 binding affinity will increase. Hence, this crucial factor must be taken into account for any further inhibitory approaches towards RBD-ACE2 interaction.
. 2021 Jul 26;11(1):15162.
doi: 10.1038/s41598-021-94602-w.
S494 O-glycosylation site on the SARS-CoV-2 RBD affects the virus affinity to ACE2 and its infectivity; a molecular dynamics study
Shadi Rahnama[SUP] 1 [/SUP], Maryam Azimzadeh Irani[SUP] 2 [/SUP], Mehriar Amininasab[SUP] 3 [/SUP], Mohammad Reza Ejtehadi[SUP] 4 [/SUP]
Affiliations
- PMID: 34312429
- DOI: 10.1038/s41598-021-94602-w
Abstract
SARS-CoV-2 is a strain of Coronavirus family that caused the ongoing pandemic of COVID-19. Several studies showed that the glycosylation of virus spike (S) protein and the Angiotensin-Converting Enzyme 2 (ACE2) receptor on the host cell is critical for the virus infectivity. Molecular Dynamics (MD) simulations were used to explore the role of a novel mutated O-glycosylation site (D494S) on the Receptor Binding Domain (RBD) of S protein. This site was suggested as a key mediator of virus-host interaction. By exploring the dynamics of three O-glycosylated models and the control systems of unglcosylated S4944 and S494D complexes, it was shown that the decoration of S494 with elongated O-glycans results in stabilized interactions on the direct RBD-ACE2. Calculation of the distances between RBD and two major H1, H2 helices of ACE2 and the interacting pairs of amino acids in the interface showed that the elongated O-glycan maintains these interactions by forming several polar contacts with the neighbouring residues while it would not interfere in the direct binding interface. Relative binding free energy of RBD-ACE2 is also more favorable in the O-glycosylated models with longer glycans. The increase of RBD binding affinity to ACE2 depends on the size of attached O-glycan. By increasing the size of O-glycan, the RBD-ACE2 binding affinity will increase. Hence, this crucial factor must be taken into account for any further inhibitory approaches towards RBD-ACE2 interaction.