Critical Interactions Between the SARS-CoV-2 Spike Glycoprotein and the Human ACE2 Receptor

Taka E., Yilmaz S. Z., Golcuk M., Kilinc C., Aktas U., Yildiz A., ...Daha Fazla

JOURNAL OF PHYSICAL CHEMISTRY B, cilt.125, sa.21, ss.5537-5548, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 125 Sayı: 21
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1021/acs.jpcb.1c02048
  • Dergi Adı: JOURNAL OF PHYSICAL CHEMISTRY B
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, Aquatic Science & Fisheries Abstracts (ASFA), Chemical Abstracts Core, Chimica, Compendex, Computer & Applied Sciences, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.5537-5548
  • İstanbul Teknik Üniversitesi Adresli: Evet

Özet

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.