SARS-CoV-2 Delta Variant is Recognized Through GRP78 Host-Cell Surface Receptor, In Silico Perspective

Area of Science:

• Virology
• Molecular Biology
• Biochemistry

Background:

• Emerging SARS-CoV-2 variants, like the delta variant (B.1.617), pose significant global health threats.
• The delta variant features E484Q and L452R mutations in its spike Receptor Binding Domain (RBD).
• Previous predictions suggested host cell receptor Glucose Regulated Protein 78 (GRP78) may recognize SARS-CoV-2 spike proteins.

Purpose of the Study:

• To investigate the binding affinity of the host cell receptor GRP78 to the SARS-CoV-2 delta variant spike RBD.
• To assess the binding interaction between the ACE2 receptor and the delta variant RBD.
• To validate the role of GRP78 in viral entry.

Main Methods:

• Molecular docking simulations were employed to analyze GRP78-delta variant spike RBD interactions.
• Molecular dynamics simulations were performed for up to 100 nanoseconds.
• Protein-protein docking was utilized to study ACE2-RBD interactions.

Main Results:

• GRP78 exhibited comparable average binding affinities to both wildtype and delta variant spike RBDs.
• The binding affinity results support the hypothesis of GRP78's involvement in SARS-CoV-2 recognition.
• ACE2-RBD interactions were also evaluated through protein-protein docking.

Conclusions:

• GRP78 plays a role in SARS-CoV-2 spike protein recognition.
• GRP78 may serve as an auxiliary pathway for viral entry into host cells.
• These findings contribute to understanding SARS-CoV-2 variant infectivity mechanisms.