Binding of SARS-CoV-2/SARS-CoV spike protein with human ACE2 receptor

Abstract

SARS-CoV-2 virus is the serious health concern throughout the world. A comprehensive investigation of binding of SARS-CoV-2 active site with host receptor protein hACE2 is important in designing effective drugs. In the present work, the major amino acid binding partners between the virus CTD and host receptor have been studied and are compared with SARS-CoV RBD binding with hACE2. Our investigation show that some unique hydrogen bond pairs which were not reported in previous work. Along with hydrogen bonding, salt-bridges, hydrophobic interactions and contributions of electrostatic and van der Waals contacts play significant role in binding mechanism. The binding affinity of SARS-CoV-2 CTD/hACE2 is greater than SARS-CoV RBD/hACE2. This outcome is also verified from the free energy estimation by using umbrella sampling.

Structural and functional insights into the spike protein mutations of emerging SARS-CoV-2 variants

“…K417N mutation is positioned at one of the key determining sites of RBD that is associated with reduced binding with hACE2 receptor. The residue Lys417 forms hydrogen-bonded and salt bridge interactions with Gln24 and Asp30 residues, respectively, of hACE2 receptor [80] (Fig. 5C).…”

Insights from in silico study of receptor energetics of SARS-CoV-2 variants

“…The optimal value of spacing was determined concerning two things: umbrella windows should not be too far apart so that there is no sufficient sampling in between the windows but also not very close so that number of windows required to sample the entire reaction pathway is unmanageably high due to computational cost. As reported in our earlier work, 12 the windows that are successively spaced 1 Å apart along the reaction coordinate proved to provide sufficient sampling (Fig. S1-S3, ESI †) and we only needed altogether ten windows in each of the six variants.…”

“…The protein backbone was used to measure the deviation of C a atoms from their initial configuration. In our previous work, 12 we performed a 250 ns MD simulation of SARS-CoV-2 WT. Since we did not find any significant deviation of RMSD from its average value and the results of our simulation were consistent with works that used much greater simulation time (such as 500 ns and 1 ms in Ali et al (2020) 10 ).…”

“…Several computational research studies have been performed to better understand the role of S protein RBD in the entry mechanism [10][11][12] and many others have attempted to determine the relative order of the binding affinity of different SARS-CoV-2 variants with hACE2 receptor. [13][14][15][16][17][18][19] For instance, Kim et al (2021) 20 conducted steered molecular dynamics (SMD) simulations and microscale thermophoresis (MST) experiments to evaluate the order of binding interaction of RBD of Alpha, Beta, gamma, Delta, Epsilon, and Kappa with the human ACE2.…”

Estudio bibliométrico de la producción científica Ecuatoriana sobre el sars cov 2 en Web of Science

“…A partir de esa premisa se identificaron las siguientes preguntas de investigación: ¿Qué fuentes de información son de valor sobre el SARS COV 2, a través de las métricas de autores principales y filiación institucional?, ¿Qué estudios se han abordado sobre la evolución de la producción científica sobre el SARS COV 2?. Considerando este contexto, el objetivo de este estudio es desarrollar un análisis bibliométrico sobre la producción científica ecuatoriana del COVID-19, dentro de la base de datos Web of Science (WOS) (Felice y Polimeni, 2020;Zyoud y Al-Jabi, 2020;Koirala et al, 2021).…”