Androgen receptor, a possible anti-infective therapy target and a potent immune respondent in SARS-CoV-2 spike binding: a computational approach

Ashfaq Ahmad, Zhandaulet Makhmutova, Wenwen Cao, Sidra Majaz, Amr Amin, Yingqiu Xie

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Background: Although androgen in gender disparity of COVID-19 has been implied, no direct link has been provided. Research design and methods: Here, we applied AlphaFold multimer, network and single cells database analyses to highlight specificity of Androgen receptor (AR) against spike receptor binding protein (RBD) of SARS-CoV-2. Results: LXXL motifs in spike RBD are essential for AR binding. RBD LXXA mutation complex with the AR depicting slightly reduced binding energy, as LXXLL motif usually mediates nuclear receptor binding to coregulators. Moreover, AR preferred to bind a LYRL motif in specificity and interaction interface, and showed reduced affinity against Omicron compared to other variants (alpha, beta, gamma, and delta). Importantly, RBD LYRL motif is a conserved antigenic epitope (9 residues) for T-cell response. Network analysis of AR-related genes against COVID-19 database showed T-cell signaling regulation, and CD8+ T-cell spatial location in AR+ single cells, which is consistent with the AR binding motif LYRL in epitope function. Conclusions: We provided the potent mechanisms of AR binding to RBD linking to immune response and vaccination shift. AR could be an anti-infective therapy target for anti-Omicron new lineages.

Original languageEnglish
Pages (from-to)317-327
Number of pages11
JournalExpert Review of Anti-Infective Therapy
Volume21
Issue number3
DOIs
Publication statusPublished - 2023

Keywords

  • Androgen receptor
  • COVID-19
  • Immune response
  • LXXL motif
  • LXXLL motif
  • Prostate cancer

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)
  • Infectious Diseases
  • Virology

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