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


Ahmad A. Makhmutova Z. Cao W. Majaz S. Amin A. Xie Y.
2023Taylor and Francis Ltd.

Expert Review of Anti-Infective Therapy
2023#21Issue 3317 - 327 pp.

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.

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

Text of the article Перейти на текст статьи

Department of Bioinformatics, Hazara University, Mansehra, Pakistan
Department of Biology, School of Sciences and Humanities, Nazarbayev University, Astana, Kazakhstan
Respiratory Department, The Second Affiliated Hospital of Shandong First Medical University, Shandong, Tai’an, China
Biology Department, UAE University, Al Ain, United Arab Emirates

Department of Bioinformatics
Department of Biology
Respiratory Department
Biology Department

10 лет помогаем публиковать статьи Международный издатель

Книга Публикация научной статьи Волощук 2026 Book Publication of a scientific article 2026