Biology subjects

El Moussaoui, M.

Publications and source records attributed to El Moussaoui, M..

2 recordsLinked to original sources

bioRxiv2026

A Unified Agent-Enabled Platform for Drug Repurposing across Molecular, Phenotypic, and Clinical Scales

Drug repurposing offers an effective path to new therapies, yet existing computational approaches rely on a single line of evidence and are rarely validated across biological scales. We present LinkD, an integrated framework that unifies diffusion-based affinity prediction, proteome-wide selectivity scoring, phenotypic validation, and population-scale clinical evidence. LinkD-Bind predicts binding across 14,981 drugs and 20,385 human targets, ranking first in 8 of 9 BindingDB, Davis, and KIBA evaluations, with the largest gains under cold-start conditions. LinkD-Select recovers 95.3% of known drug-target pairs by combining selectivity scoring and molecular docking. LinkD-Pheno integrates drug-sensitivity and CRISPR dependency data across 960 cancer cell lines, identifying 34 novel drug-gene pairs and recovering [~]85% of known targets among the top 50 candidates. Across 11.5 million individuals from Mount Sinai and UK Biobank, LinkD-prioritized {beta}-blockers propranolol (HR 0.82) and carvedilol (HR 0.92) reduced 5-year prostate cancer incidence relative to metoprolol, corroborated by ADRB2 docking and LNCaP growth inhibition. LinkD-Agent, which can effectively orchestrate all evidence layers, is served on a publicly available web platform (https://linkd-agent.onrender.com/), enabling a wide range of users to derive new drug repurposing opportunities through natural language queries.

bioinformatics↗

bioRxiv2025

Pure CD32+ CD4+ Cells Are Cytotoxic Memory CD4+ T Lymphocytes Highly Enriched for HIV-1 DNA

The elusive viral reservoir is the major obstacle to an HIV-1 cure. Cell surface protein CD32 has been proposed to pinpoint cells with a very high proviral enrichment, potentially providing a tool for selective therapeutic targeting of the reservoir. However, this finding has been challenged by subsequent reports. In order to clarify the nature of CD32 expression on CD4+ T cells, here we designed a purification strategy allowing single-cell analysis using state-of-the-art technologies. The established multilevel sorting strategy allowed to characterize a rare (median 0.06% of CD4+ T cells) but bona fide CD32+ CD4+ T-cell population. In vitro cell stimulation could not lead to CD32 upregulation. Detailed phenotyping revealed that CD32+ T cells reside mostly in the memory T-cell compartment with heightened levels of acute and chronic activation markers. Single-cell RNA sequencing identified that CD32+ CD4+ T cells are mostly highly cytotoxic CD4+ cells. Importantly. in HIV-1 infected donors under suppressive antiretroviral therapy, we found that these cells are highly enriched for HIV-1 provirus, harbor a clear cytotoxic memory T-cell transcriptome, as well as TCR clonal enrichment. These findings indicate that CD32 remains a promising candidate marker of the HIV-1 reservoir and underline the importance of further investigation of this marker during latent infection.

immunology↗