Omicron variants bind to human angiotensin-converting enzyme 2 (ACE2) much stronger due to higher number of charged-charged interactions

KALYONCU UZUNLAR S.

Biotech Studies, vol.32, no.2, pp.75-82, 2023 (Scopus, TRDizin)

  • Publication Type: Article / Article
  • Volume: 32 Issue: 2
  • Publication Date: 2023
  • Doi Number: 10.38042/biotechstudies.1332403
  • Journal Name: Biotech Studies
  • Journal Indexes: Scopus, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.75-82
  • Keywords: Angiotensin-converting enzyme 2 (ACE2), Coronavirus disease 2019 (COVID-19), Omicron, Receptor binding domain (RBD), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
  • Dokuz Eylül University Affiliated: Yes

Abstract

Since the start of COVID-19 pandemic, several mutant variants of SARS-CoV-2 have emerged with different virulence and transmissibility patterns. Some of these variants have been labeled as variants of concern (VOC). There are mainly five strain clades with VOC status: Alpha, Beta, Gamma, Delta, and Omicron. Omicron sub-variants have been currently in circulation around the world, and they show faster transmissibility and lower virulence compared to others. Receptor binding domain (RBD) of SARS-CoV-2 spike protein is the region where it binds to human angiotensin-converting enzyme 2 (hACE2) on the host cell. Mutations on RBD might have direct or indirect effects on differential disease patterns of these variants. In this study, we analyzed sequence and structures of SARS-CoV-2 variants’ RBD domains and documented their predicted affinities and contact interactions with hACE2. We found that Omicron sub-variants have much higher hACE2 affinities compared to other VOC strains. To understand reasons behind this, we checked biophysical characteristics of RBD-hACE2 contacts. Surprisingly, number of charged-charged interactions of Omicron sub-variants were on average 4-fold higher. These higher charged residue mutations on epitope region of Omicron sub-variants leading to stronger affinity for hACE2 might shed light onto why Omicron has less severe disease symptoms.