Structural and simulation analysis of hotspot residues interactions of SARS-CoV 2 with human ACE2 receptor

Abstract

The novel corona virus disease 2019 (SARS-CoV 2) pandemic outbreak was alarming. The binding of SARS-CoV (CoV) spike protein (S-Protein) Receptor Binding Domain (RBD) to Angiotensin converting enzyme 2 (ACE2) receptor initiates the entry of corona virus into the host cells leading to the infection. However, considering the mutations reported in the SARS-CoV 2 (nCoV), the structural changes and the binding interactions of the S-protein RBD of nCoV were not clear. The present study was designed to elucidate the structural changes, hot spot binding residues and their interactions between the nCoV S-protein RBD and ACE2 receptor through computational approaches. Based on the sequence alignment, a total of 58 residues were found mutated in nCoV S-protein RBD. These mutations led to the structural changes in the nCoV S-protein RBD 3d structure with 4 helices, 10 sheets and intermittent loops. The nCoV RBD was found binding to ACE2 receptor with 11 hydrogen bonds and 1 salt bridge. The major hot spot amino acids involved in the binding identified by interaction analysis after simulations includes Glu 35, Tyr 83, Asp 38, Lys 31, Glu 37, His 34 amino acid residues of ACE2 receptor and Gln 493, Gln 498, Asn 487, Tyr 505 and Lys 417 residues in nCoV S-protein RBD. Based on the hydrogen bonding, RMSD and RMSF, total and potential energies, the nCoV was found binding to ACE2 receptor with higher stability and rigidity. Concluding, the hotspots information will be useful in designing blockers for the nCoV spike protein RBD.

Emerging of composition variations of SARS-CoV-2 spike protein and human ACE2 contribute to the level of infection: in silico approaches

“…Study by Amin et al ( 2020 ) reported hACE2 receptor [E329] variant with SARS-CoV spike protein with high contribution for binding energy. Recently, a study proved that wild hACE2 receptor and SARS-CoV-2 spike protein (–35.33 Kcal/mol) are having a stable interaction and are present at the moderate zone similar to the present results (Veeramachaneni et al, 2020 ). Previous study reported that SARS-CoV-2 spike protein [G476S] variant has a significant very strong point and a strong direct binding affinity with hACE2 receptor, and similarly, the G476S variant showed strong binding [G726R] of spike and falling in the very strong zone (Korber et al, 2020 ).…”

Traditional medicinal plants against replication, maturation and transmission targets of SARS-CoV-2: computational investigation

“…Based on the recent structural and MD studies, many key amino acid residues of the ACE2 receptor are identified in interacting with its partner proteins (Lan et al, 2020 ; Veeramachaneni et al, 2020 ). The human ACE2 receptor contains two hotspot residues Lys31 and Lys353.…”

“…Molecular docking of standard drugs and bioactives from medicinal plants with receptor molecules was performed using AutoDock Vina (Trott & Olson, 2010 ). The catalytic site of SARS-CoV-2 M pro (His41 and Cys145), receptor binding motif of S-protein (Leu455, Phe486, Glu493 and Ser494) and hotspot binding residues of ACE2 receptor (Lys31 and Lys353) were chosen as binding sites for docking analysis (Jin et al, 2020 ; Lan et al, 2020 ; Shang et al, 2020 ; Veeramachaneni et al, 2020 ; Yan et al, 2020 ). Grid box was generated using ADT with dimensions relative to the ligands (XYZ) with a resolution of 1 Å.…”

Culinary spice bioactives as potential therapeutics against SARS-CoV-2: Computational investigation

“…Based on the recent structural and molecular dynamics studies, many important amino acid residues of the ACE2 receptor are recognized in interacting with its partner proteins [ 8 , 45 ]. The human ACE2 receptor contains hotspot Lys31 and hotspot Lys353.…”