Glowacki, D. R. | Search bioRxiv

bioRxiv2025

Autonomic Indicators of Self-Transcendence: Insights from the Numadelic VR Paradigm

Self-transcendent experiences (STEs) offer profound and beneficial shifts in perspective, yet remain largely inaccessible outside elite contemplative or pharmacological contexts. Neural measures have deepened our understanding of these states, but their cost and limited ecological validity constrain broader application. This study evaluates heart rate variability (HRV) amplitude, a measure reflecting dynamic sympathovagal engagement, as a cost-effective and sustainable physiological marker of STE during numadelic virtual reality (VR) experiences. The unique numadelic aesthetic combined with multi-person can induce STE through dissolving self-boundaries and fostering embodied presence. Building on previous work linking non-ordinary states of consciousness (NOSC) with autonomic nervous system activity during psychedelic drug administration, we tested the hypothesis that HRV amplitude may reflect STE depth and relate to affective and relational outcomes during non-drug numadelic VR experiences. Specifically, ninety-six participants engaged in guided meditation within either a numadelic VR setting or a non-VR audio-guided group format. Physiological data (cardiac activity and respiration) were recorded during the meditation, alongside psychological assessments pre- and post-session. Findings confirm that HRV amplitude measured during numadelic VR correlates with subjective STE ratings. It also relates to compassion traits, and emotional improvement following VR practice. Additional analysis of data from a prior psychedelic drug study further validated the relevance of this measure across methods of inducing NOSCs. These results advance the psychophysiological mapping of STEs and highlight HRV amplitude as a potential real-time biomarker which may help to guide participants toward self-transcendent states within adaptive environments. By integrating contemplative science with immersive design, this work supports the development of scalable tools that enhance both access to and understanding of STEs.

neuroscience↗

bioRxiv2021

Discovery of SARS-CoV-2 Mpro Peptide Inhibitors from Modelling Substrate and Ligand Binding

The main protease (Mpro) of SARS-CoV-2 is central to its viral lifecycle and is a promising drug target, but little is known concerning structural aspects of how it binds to its 11 natural cleavage sites. We used biophysical and crystallographic data and an array of classical molecular mechanics and quantum mechanical techniques, including automated docking, molecular dynamics (MD) simulations, linear-scaling DFT, QM/MM, and interactive MD in virtual reality, to investigate the molecular features underlying recognition of the natural Mpro substrates. Analyses of the subsite interactions of modelled 11-residue cleavage site peptides, ligands from high-throughput crystallography, and designed covalently binding inhibitors were performed. Modelling studies reveal remarkable conservation of hydrogen bonding patterns of the natural Mpro substrates, particularly on the N-terminal side of the scissile bond. They highlight the critical role of interactions beyond the immediate active site in recognition and catalysis, in particular at the P2/S2 sites. The binding modes of the natural substrates, together with extensive interaction analyses of inhibitor and fragment binding to Mpro, reveal new opportunities for inhibition. Building on our initial Mpro-substrate models, computational mutagenesis scanning was employed to design peptides with improved affinity and which inhibit Mpro competitively. The combined results provide new insight useful for the development of Mpro inhibitors.

bioinformatics↗