Biology subjects

Vasan, S. S.

Publications and source records attributed to Vasan, S. S..

6 recordsLinked to original sources

bioRxiv2026

Experimental validation of computationally prioritized bisphosphonates reveals no direct in vitro antiviral activity against SARS-CoV-2

It is essential to experimentally evaluate antiviral efficacy predicted by molecular docking and related in silico approaches, which this study achieves for three bisphosphonates (alendronate, minodronate, zoledronate) and treprostinil, identified as potential antiviral therapies in our previous work. These investigational compounds had no detectable cytotoxicity at concentrations up to 25M in Vero E6 cells but also failed to show any antiviral effect against the PQ.8.1 isolate of SARS-CoV-2, when compared to control drugs (ensitrelvir, nirmatrelvir, and remdesivir). It appears that for bisphosphonates, any protective effect is likely due to other virus- or host-mediated mechanisms of action. This study demonstrates the importance of iterating between theoretical hypotheses and experiments to elucidate underlying mechanisms at play.

molecular biology↗

bioRxiv2025

Participatory development of innovation and implementation strategy - a practical approach

BackgroundHealthcare and academic institutions face growing challenges in strategic planning due to rapid advances in medicine and technology, alongside fiscal and workforce constraints that limit traditional consultation. Participatory approaches offer a way to integrate diverse stakeholder perspectives under these constraints, generating contextually relevant strategies that can indicate whether current directions are appropriate or whether priorities have been overlooked. MethodsA structured participatory workshop was conducted at the 10th Grampian Research Conference (June 2025). One hundred seventy-eight participants including National Health Service (NHS) staff, academics, industry partners, patients, and public contributors, engaged in 14 parallel roundtable discussions. Contributions were captured using posters and Post-it notes, collecting 148 written annotations. Data were analysed using thematic and content analysis, supplemented by strategic frameworks including Strengths, Weaknesses, Opportunities and Threats (SWOT/TOWS), and Easy Wins, to identify and prioritise actionable strategies. ResultsFive core themes emerged: (1) access to healthcare and services, (2) patient and public involvement and engagement, (3) digital health and service delivery innovation, (4) data access, integration, and governance, and (5) workforce development and culture. SWOT analysis identified strengths in telemedicine, interdisciplinary student training, and patient and public involvement, alongside weaknesses in fragmented data, referral tracking, and workforce pressures. TOWS matrix produced strategy-oriented recommendations such as AI-enabled scheduling, remote monitoring, and transparent referral systems. Easy Wins framework assessment highlighted immediate, low-cost improvements including identifiable NHS caller identification, automated text message reminders, updated informational videos and multilingual materials. ConclusionBy combining participatory outputs with structured strategy tools, this approach demonstrated a resource-efficient model for adaptive planning. The findings align with and extend current national health policy frameworks, offering a replicable approach for institutions aiming to obtain meaningful stakeholder engagement despite fiscal and temporal constraints.

scientific communication and education↗

bioRxiv2024

Use of Stem Cell-Derived Cardiomyocyte and Nasal Epithelium Models to Establish a Multi-Tissue Model Platform to Validate Repurposed Drugs Against SARS-CoV-2 Infection

The novel coronavirus disease (COVID-19) and any future coronavirus outbreaks will require more affordable, effective and safe treatment options to complement current ones such as Paxlovid. Drug repurposing can be a promising approach if we are able to find a rapid, robust and reliable way to down-select and screen candidates using in silico and in vitro approaches. With repurposed drugs, ex vivo models could offer a rigorous route to human clinical trials with less time invested into nonclinical animal (in vivo) studies. We have previously shown the value of commercially available ex vivo/3D airway and alveolar tissue models, and this paper takes this further by developing and validating human nasal epithelial model and embryonic stem cells derived cardiomyocyte model. Five shortlisted candidates (fluvoxamine, everolimus, pyrimethamine, aprepitant and sirolimus) were successfully compared with three control drugs (remdesivir, molnupiravir, nirmatrelvir) when tested against key variants of the SARS-CoV-2 virus including Delta and Omicron, and we were able to reconfirm our earlier finding that fluvoxamine can induce antiviral efficacy in combination with other drugs. Scalability of this high-throughput screening approach has been demonstrated using a liquid handling robotic platform for future Disease-X outbreaks.

microbiology↗

bioRxiv2022

Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies Against Delta and Omicron in Mice

As existing vaccines fail to completely prevent COVID-19 infections or community transmission, there is an unmet need for vaccines that can better combat SARS-CoV-2 variants of concern (VOC). We have previously developed highly thermo-tolerant monomeric and trimeric receptor binding domain derivatives that can withstand 100{degrees}C for 90 minutes and 37{degrees}C for four weeks, and help eliminate cold chain requirements. We show that mice immunised with these vaccine formulations elicit high titres of antibodies that neutralise SARS-CoV-2 variants VIC31 (with Spike: D614G mutation), Delta and Omicron (BA.1.1) VOC. Compared to VIC31, there was an average 14.4-fold reduction in neutralisation against BA.1.1 for the three monomeric antigen-adjuvant combinations, and 16.5-fold reduction for the three trimeric antigen-adjuvant combinations; the corresponding values against Delta were 2.5 and 3.0. Our findings suggest that monomeric formulations are suitable for the upcoming Phase I human clinical trials, and that there is potential for increasing efficacy with vaccine matching to improve responses against emerging variants. These findings are consistent with in silico modelling and AlphaFold predictions which show that while oligomeric presentation can be generally beneficial, it can make important epitopes inaccessible, and also carries the risk of eliciting unwanted antibodies against the oligomerisation domain.

immunology↗

bioRxiv2021

But Mouse, you are not alone: On some severe acute respiratory syndrome coronavirus 2 variants infecting mice

In silico predictions combined with in vitro, in vivo and in situ observations collectively suggest that mouse adaptation of the SARS-CoV-2 virus requires an aromatic substitution in position 501 or position 498 (but not both) of the spike proteins receptor binding domain. This effect could be enhanced by mutations in positions 417, 484, and 493 (especially K417N, E484K, Q493K and Q493R), and to a lesser extent by mutations in positions 486 and 499 (such as F486L and P499T). Such enhancements due to more favourable binding interactions with residues on the complementary angiotensin-converting enzyme 2 (ACE2) interface, are however, unlikely to sustain mouse infectivity on their own based on theoretical and experimental evidence to date. Our current understanding thus points to the Alpha, Beta, Gamma, and Omicron variants of concern infecting mice, while Delta and Delta Plus lack a similar biomolecular basis to do so. This paper identifies eleven countries (Brazil, Chile, Djibouti, Haiti, Malawi, Mozambique, Reunion, Suriname, Trinidad and Tobago, Uruguay and Venezuela) where targeted local field surveillance of mice is encouraged because they may have come in contact with humans who had the virus with adaptive mutation(s). It also provides a systematic methodology to analyze the potential for other animal reservoirs and their likely locations.

bioinformatics↗

bioRxiv2021

Live virus neutralisation of the 501Y.V1 and 501Y.V2 SARS-CoV-2 variants following INO-4800 vaccination of ferrets

The ongoing COVID-19 pandemic has resulted in significant global morbidity and mortality on a scale similar to the influenza pandemic of 1918. Over the course of the last few months, a number of SARS-CoV-2 variants have been identified against which vaccine-induced immune responses may be less effective. These "variants-of-concern" have garnered significant attention in the media, with discussion around their impact on the future of the pandemic and the ability of leading COVID-19 vaccines to protect against them effectively. To address concerns about emerging SARS-CoV-2 variants affecting vaccine-induced immunity, we investigated the neutralisation of representative G614, 501Y.V1 and 501Y.V2 virus isolates using sera from ferrets that had received prime-boost doses of the DNA vaccine, INO-4800. Neutralisation titres against G614 and 501Y.V1 were comparable, but titres against the 501Y.V2 variant were approximately 4-fold lower, similar to results reported with other nucleic acid vaccines and supported by in silico biomolecular modelling. The results confirm that the vaccine-induced neutralising antibodies generated by INO-4800 remain effective against current variants-of-concern, albeit with lower neutralisation titres against 501Y.V2 similar to other leading nucleic acid-based vaccines.

immunology↗