Gender trend of monkeypox virus infection.

INTRODUCTION: An outbreak of monkeypox (mpox) in 2022 has been declared as a 'public health emergency of international concern' by the World Health Organization (WHO). There are many reports about the cases of male-to-male transmission of the recent mpox virus (MPXV). However, the mechanism and trend of male infection are unclear. We analyzed public data to test whether men are vulnerable to mpox by gender effect. AREAS COVERED: Public data of previously and recently reported cohort cases, including gender information of MPXV-infected patients, from PubMed, Google Scholar, and EBSCO databases were collected and analyzed. Network analysis was used to explore the potent intersections between male hormone receptor, androgen receptor (AR) signaling, and mpox-related and -infected host cell response genes. Furthermore, gene ontology enrichment and KEGG genomic signaling pathways were analyzed using intersection genes. EXPERT OPINION: MPXV infections among the male population are more frequent than the female population using multiple cohort public data analysis. AR signaling-related gene list against mpox host cell response gene list data of two sets showed that the most intersection genes are related to human immunodeficiency virus (HIV) infection, inflammation, and transcription. AR signaling may be essential to the infection and might be a potent target in anti-mpox infective therapy.

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

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.