Open AccessCritical Interactions Between the SARS-CoV-2 Spike Glycoprotein and the Human ACE2 Receptor
Author(s) -
Elhan Taka,
Sema Zeynep Yilmaz,
Mert Gölcük,
Ceren Kılınç,
Umut Aktas,
Ahmet Yıldız,
Mert Gür
Publication year - 2021
Publication title -
the journal of physical chemistry. b
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 392
eISSN - 1520-6106
pISSN - 1520-5207
DOI - 10.1021/acs.jpcb.1c02048
Subject(s) - glycoprotein , coronavirus , receptor , biophysics , mutagenesis , covid-19 , chemistry , angiotensin converting enzyme 2 , plasma protein binding , hydrophobic effect , molecular dynamics , binding site , virology , microbiology and biotechnology , mutation , biology , biochemistry , gene , medicine , disease , computational chemistry , pathology , infectious disease (medical specialty)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells by binding its spike (S) glycoproteins to angiotensin-converting enzyme 2 (ACE2) receptors and causes the coronavirus disease 2019 (COVID-19). Therapeutic approaches to prevent SARS-CoV-2 infection are mostly focused on blocking S-ACE2 binding, but critical residues that stabilize this interaction are not well understood. By performing all-atom molecular dynamics (MD) simulations, we identified an extended network of salt bridges, hydrophobic and electrostatic interactions, and hydrogen bonds between the receptor-binding domain (RBD) of the S protein and ACE2. Mutagenesis of these residues on the RBD was not sufficient to destabilize binding but reduced the average work to unbind the S protein from ACE2. In particular, the hydrophobic end of RBD serves as the main anchor site and is the last to unbind from ACE2 under force. We propose that blocking the hydrophobic surface of RBD via neutralizing antibodies could prove to be an effective strategy to inhibit S-ACE2 interactions.