Computational biophysical characterization of the SARS-CoV-2 spike protein binding with the ACE2 receptor and implications for infectivity.

Computational and Structural Biotechnology Journal
R. ChowdhuryCostas D Maranas

Abstract

SARS-CoV-2 is a novel highly virulent pathogen which gains entry to human cells by binding with the cell surface receptor - angiotensin converting enzyme (ACE2). We computationally contrasted the binding interactions between human ACE2 and coronavirus spike protein receptor binding domain (RBD) of the 2002 epidemic-causing SARS-CoV-1, SARS-CoV-2, and bat coronavirus RaTG13 using the Rosetta energy function. We find that the RBD of the spike protein of SARS-CoV-2 is highly optimized to achieve very strong binding with human ACE2 (hACE2) which is consistent with its enhanced infectivity. SARS-CoV-2 forms the most stable complex with hACE2 compared to SARS-CoV-1 (23% less stable) or RaTG13 (11% less stable). Notably, we calculate that the SARS-CoV-2 RBD lowers the binding strength of angiotensin 2 receptor type I (ATR1) which is the native binding partner of ACE2 by 44.2%. Strong binding is mediated through strong electrostatic attachments with every fourth residue on the N-terminus alpha-helix (starting from Ser19 to Asn53) as the turn of the helix makes these residues solvent accessible. By contrasting the spike protein SARS-CoV-2 Rosetta binding energy with ACE2 of different livestock and pet species we find strongest binding w...Continue Reading

References

Nov 24, 1986·Physical Review Letters·R H Swendsen, J S Wang
Feb 3, 2004·The Journal of Biological Chemistry·Paul TowlerMichael W Pantoliano
Mar 11, 2004·Journal of Computational Chemistry·Yang Zhang, Jeffrey Skolnick
Jul 12, 2007·Proteins·Julian MintserisZhiping Weng
Sep 6, 2011·Nucleic Acids Research·Mikhail A LomizeAndrei L Lomize
Apr 27, 2012·International Journal of Peptides·Chris Tikellis, M C Thomas
Nov 10, 2012·Protein Science : a Publication of the Protein Society·P Benjamin Stranges, Brian Kuhlman
Apr 13, 2013·Journal of Computer-aided Molecular Design·G Madhavi SastryWoody Sherman
Dec 3, 2014·Journal of Computational Chemistry·Robert J PantazesCostas D Maranas
Apr 18, 2015·Nucleic Acids Research·Jianyi Yang, Yang Zhang
Apr 22, 2017·Journal of Chemical Theory and Computation·Rebecca F AlfordJeffrey J Gray
Feb 26, 2020·International Journal of Oral Science·Hao XuQianming Chen
Mar 11, 2020·Cell·Alexandra C WallsDavid Veesler
Mar 15, 2020·The Lancet. Respiratory Medicine·Lei FangMichael Roth
Apr 25, 2020·International Journal of Molecular Sciences·Ayumu AsaiHideshi Ishii
May 29, 2020·The Journal of Physical Chemistry Letters·Angelo SpinelloAlessandra Magistrato
Jun 12, 2020·The Journal of Infectious Diseases·Bruna G G PintoHelder I Nakaya
Jun 27, 2020·BioRxiv : the Preprint Server for Biology·Tyler N StarrJesse D Bloom
Dec 12, 2020·Cell·Alexandra C WallsDavid Veesler

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Citations

Dec 3, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Loai M SaadahIman A Basheti
Mar 25, 2021·Computational and Structural Biotechnology Journal·Ettore Lo CascioAlessandro Arcovito
Jun 18, 2021·Physical Chemistry Chemical Physics : PCCP·Zhendong Li, John Z H Zhang

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Methods Mentioned

BETA
co-immunoprecipitation

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