McLellan, S. | Search bioRxiv

bioRxiv2026

Community-Based Surveillance for Highly Pathogenic Avian Influenza Viruses among Deceased Birds

Highly pathogenic avian influenza (HPAI) viruses of H5N1 clade 2.3.4.4b, are spreading worldwide, posing a threat to wildlife, domestic animals, and humans. In 2025, a multidisciplinary collaboration for HPAI H5N1 surveillance among birds within Galveston County, Texas, was initiated. Between November and December 2025, oropharyngeal and cloacal swabs were collected from wild and domestic birds reported as dead or dying by Galveston County residents. Specimens were studied with molecular assays, Sanger sequencing, virus isolation, and next-generation sequencing. Molecular evidence of HPAI H5N1 was detected in 7 of 10 (70%) birds, and the virus was successfully cultured in MDCK cells. Next-generation sequencing analysis of eight influenza A genome segments demonstrated a 4:4 gene segment reassortant constellation within clade 2.3.4.4b, consistent with genotype D1.1. Community members exposed to HPAI were offered antiviral prophylaxis. No human infections were identified. This surveillance demonstrates that community involvement combined with cross-sectoral collaboration can ensure rapid detection and characterization of circulating avian influenza viruses. Sustained local surveillance is essential for early warning, risk assessment, and prevention of virus spread to poultry, mammals, and humans.

molecular biology↗

bioRxiv2025

SyntheMol-RL: a flexible reinforcement learning framework for designing novel and synthesizable antibiotics

The rise of antibiotic-resistant pathogens such as Staphylococcus aureus has created an urgent need for new antibiotics. Generative artificial intelligence (AI) has shown promise in drug discovery, but existing models often fail to propose compounds that are both effective and synthetically tractable. To address these challenges, we introduce SyntheMol-RL, a reinforcement learning-based generative model that can rapidly design synthetically accessible small molecule drug candidates from a massive chemical space of 46 billion compounds. SyntheMol-RL improves upon our prior Monte Carlo Tree Search (MCTS)-based SyntheMol model by generalizing across chemically similar building blocks and enabling multi-parameter optimization. We applied SyntheMol-RL to generate candidate antibiotics against S. aureus by optimizing for both antibacterial activity and aqueous solubility, and we found that SyntheMol-RL generated molecules with improved predicted properties compared to both the previous MCTS version of SyntheMol as well as an AI-based virtual screening baseline. We synthesized 79 SyntheMol-RL compounds that were unique relative to the training dataset and found that 13 showed potent in vitro activity, of which seven were structurally novel after detailed literature searches. Furthermore, one hit compound, synthecin, demonstrated efficacy in a murine wound infection model of methicillin-resistant S. aureus (MRSA). These results validate SyntheMol-RLs ability to generate novel and synthetically accessible candidate antibiotics and position SyntheMol-RL as a powerful tool for drug design across therapeutic domains.

biochemistry↗