Biology subjects

Davison, G.

Publications and source records attributed to Davison, G..

3 recordsLinked to original sources

bioRxiv2025

A Novel dual Influenza virus and SARS-CoV-2 neutralisation assay

Influenza and SARS-CoV-2 are co-circulating during the traditional influenza season giving rise to potential co-infections; currently estimated at 2.4%. Additionally, this means that the uptake of both vaccines (including SARS-CoV-2 boosters) will be encouraged within the same timeframe. Currently, patients receive separate vaccines in different arms on the same or different days. Induction of neutralising antibodies (NAbs) is used as the measure of efficacy for SARS-CoV-2 vaccinations while, the hemagglutination inhibition (HI) assay is the gold standard for seasonal influenza vaccine assessment. However, with the advent of novel universal influenza vaccine and dual SARS-CoV-2/Influenza vaccine approaches it is possible that functional NAb assays will become an essential component of a vaccine assessment toolbox. This assay is capable of distinguishing NAb responses during both dual vaccination development, and as part of co-infection and imprinting studies. Taking advantage of existing pseudotyped viruses developed by us, we present herein a dual neutralisation assay, which utilises 2 different luciferase (Renilla and Firefly) reporter lentiviral vectors. We configured assays with various combinations of SARS-CoV-2 and influenza subtype/variant combinations and compared sensitivity of this dual approach to neutralisation levels seen in single virus pseudotype Micro-neutralisation (pMN) in a double-blinded test of monoclonal antibody cocktails, and subsequently with a pre-screened serum panel. Mono and dual neutralisation pMN identified correctly positive and negative samples and IC50 values were all within 2-fold of each other, suggesting that specificity and sensitivity are retained post-multiplex. As we have taken a pseudovirus based approach there is the potential to tailor to specific vaccination candidates or currently circulating strains of each virus. The use of this versatile assay could form part of the toolbox of analysis of dual vaccination candidates and investigating responses during co-infection including studies assessing the impact of immune imprinting in the future.

immunology↗

bioRxiv2022

Exercise rejuvenates the skeletal muscle methylome and transcriptome in humans

Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta-analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle samples (n = 3,176). We show that: 1) individuals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, 2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns towards a younger profile, and 3) muscle disuse "ages" the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted towards a younger state after exercise training interventions, while the transcriptome shifted towards an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age-related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity.

molecular biology↗

bioRxiv2020

Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease

COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 or MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through a combined mass spectrometry and X-ray approach against the SARS-CoV-2 main protease, one of two cysteine viral proteases essential for viral replication. Our crystallographic screen identified 71 hits that span the entire active site, as well as 3 hits at the dimer interface. These structures reveal routes to rapidly develop more potent inhibitors through merging of covalent and non-covalent fragment hits; one series of low-reactivity, tractable covalent fragments was progressed to discover improved binders. These combined hits offer unprecedented structural and reactivity information for on-going structure-based drug design against SARS-CoV-2 main protease.

biophysics↗