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The COVID-19 pandemic has shone a light on virology and highlighted the need for public engagement to convey both results and processes behind the research. We designed a 20-minute escape room (Escape Lab) to ask ‘How can antiviral drugs be identified and developed?’ Escape Lab is aimed for children (secondary school-aged and above) and adults, with no expectation of prior scientific expertise. The goal is to find the structure of a potent antiviral compound that a scientist in the lab has discovered. The activities mimicked some of the key stages of our drug-discovery research: (1) screening compounds for antiviral activity; (2) checking cytotoxicity; (3) chemically modifying hit compounds to improve potency. Teams interpreted protocols and results from the scientist’s lab notebook and undertook ‘experiments’ to generate clues for each stage. The team ‘escaped’ the lab when they built a molecular model of the antiviral compound. Successful teams were given certificates and finish times recorded on a leaderboard to generate a sense of competition. Participants could also talk with current researchers to relate the activities to real data generated in our lab. Escape Lab was run at two events (British Science Festival, Leicester and Leicester Business Festival) in 2022. We had overwhelmingly positive feedback (95% 5-stars) and ~50% of participants seeking to learn more about our research. Overall, this offers a blueprint for a fun and engaging way to bring research to the public, with the flexibility to update the scenario to incorporate novel research and target different age groups.

Aim: The emergence of three pandemic coronaviruses in the last two decades combined with numerous coronaviruses circulating in bats suggest that spillover of new coronaviruses into humans is likely in the future. The development of broad-spectrum antivirals is vital to allow rapid deployment to patients in the absence of a pan-coronavirus vaccine. This project aims to employ a model coronavirus system as an initial screening tool to identify novel natural product-derived antivirals. Methods: Antiviral activity of a panel of natural compounds and synthetic xanthones based on bioactive compounds from the medicinal plant Swertia chirayita were tested against a model seasonal human coronavirus (HCoV) OC43. Infected baby hamster kidney (BHK-21) cells were treated with compounds and impact on infectivity determined by quantifying viral titres. Alongside, cytotoxicity of the compounds was also determined. Results: Our initial screen identified six compounds that indicated antiviral activity, with synthetic xanthones showing a significant reduction in viral infectivity of HCoV-OC43 at non-cytotoxic concentrations. Preliminary experiments suggest that these inhibit the virus at early stages of the viral life cycle. Conclusions: We have identified bioactive compounds derived from Swertia chirayita, which show significant antiviral efficacy in a human coronavirus. Further work to evaluate their pan-coronavirus activity, as well as to understand the mechanism of action are on-going.

Aims: This study aimed to investigate the stability of HCoV-OC43 on leather and transfer to other surfaces and to determine the antiviral activity of a silver-based leather coating. Methods and Results: The infectivity of HCoV-OC43 (6.6 log10 TCID50) on patent, nubuck, full-grain calf and corrected grain leathers (untreated and silver-coated) was measured over 72 hours by titration on BHK-21 cells. Recovery from pig skin (8-9 log10 TCID50) was also assessed. Transfer of infectious HCoV-OC43 from leather onto cardboard and stainless steel (0-48 hours post-inoculation) was quantified. HCoV-OC43 remained infectious for 6-48 hours on patent, finished and calf leathers; no infectious HCoV-OC43 was recovered from nubuck at 0 hours. Silver coating of full-grain calf and corrected grain leathers significantly reduced HCoV-OC43 infectivity (p≤0.05) after 2 hours, where no infectious virus was recovered. Transfer of HCoV-OC43 (≤3.1-5.5 log10) was detected from calf, finished and patent leather onto stainless steel and carboard up to 2 hours after inoculation, while no transfer was detected for silver-coated leathers at 2 hours. Leather has also been utilised as a skin surrogate for investigating fomite transmission. HCoV-OC43 was reduced by 4.71 log10 on pig skin at 0 hours, in a similar trend to highly absorbent nubuck leather. Conclusions: Human coronaviruses remain infectious on leather for up to 48 hours and transfer onto cardboard and stainless steel up to 2 hours post-inoculation. Absorbency contributes to the recovery/persistence of HCoV-OC43 on surfaces. A silver-based leather coating demonstrated antiviral activity and limited viral transfer onto other surfaces. Significance of Study: This investigation suggests that leather could pose a risk of indirect transmission of human coronaviruses; this is of significance for settings where there is close contact with leathers such as in manufacturing, retail and domestic environments. A silver-based leather coating demonstrated antiviral activity and limited viral transfer onto other surfaces, reducing the potential for indirect transmission from leathers.

Aims The aim of this investigation was to determine the persistence of human coronaviruses on a range of textiles both in the environment and during laundering. Methods and Results The stability of human coronaviruses HCoV-OC43 and HCoV-229E on cotton, polycotton and polyester textiles was determined up to 72 hours. The transfer of HCoV-OC43 from textiles to plastic or another textile was quantified. Persistence of HCoV-OC43 on cotton during domestic and industrial laundering was also investigated in the presence and absence of detergents and temperature (40-75°C). Infectious virus was quantified by titration on mammalian cells. Infectious HCoV-OC43 was detectable for 6 hours on polycotton, 24 hours on cotton and ≥72 hours on polyester. HCoV-229E was less stable, where it was detectable for 2 hours on polycotton, 6 hours on cotton and 24 hours on polyester. HCoV-OC43 transferred from polyester to PVC and polyester up to 72 hours post-inoculation, whereas no transfer was detected from cotton or polycotton. Domestic and industrial laundering without temperature and detergent completely removed HCoV-OC43 from cotton (≥ 4.58 log10 reduction) under clean conditions. Under dirty conditions, HCoV-OC43 was detected on cotton (≤1.78 log10) after domestic laundering without temperature and detergent. However, HCoV-OC43 was removed by domestic laundering with temperature (40°C) and detergent, or industrial laundering without temperature and detergent. Conclusions Human coronaviruses can persist on textiles for up to 3 days and readily transfer from polyester to other surfaces. HCoV-OC43 were removed from cotton during both domestic and industrial laundering. Significance of Study Polyester could potentially act as fomites for the transmission of coronaviruses, demonstrating the importance of infection control procedures for handling of contaminated textiles. Human coronaviruses are removed from textiles during common domestic and industrial wash programmes, indicating that typical healthcare washing procedures are likely to be suitable for decontaminating textiles.

Previous research indicates that SARS-CoV-2 persists on stainless steel and plastic for 72 hours to 7 days and appears to be less stable on porous surfaces. However, there is limited research on the stability of coronaviruses on a range of textiles, of which the composition and construction could have an effect on its persistence. Determination of the persistence of coronaviruses on textiles is required to evaluate the potential risk of fomite transmission via textiles; this is of particular importance in healthcare settings to inform laundering policies for the adequate decontamination of hospital linens and staff uniforms. The aim of this study is to determine the stability of model human coronaviruses for SARS-CoV-2 on a range of textile fibres and how best to decontaminate them. Human coronavirus (HCoV) OC43 was cultured on HCT-8 cells and HCoV-229E was cultured on MRC-5 cells. The optimal recovery method of virus from textiles was first determined by comparing the recovery efficiency of HCoV-OC43 from 100% cotton using differing diluents (cell culture media, phosphate buffered saline (PBS) and maximum recovery diluent (MRD)) and recovery methods (vortexing, stomaching and shaking by hand). The stability of HCoV-OC43 and HCoV-229E was then determined on 100% cotton, polyester/cotton blend, 100% polyester and calf leather up to 48 hours. A no virus (culture media only) control was included. Infectious virus was quantified by titration of the supernatant on BHK-21 cells in 96-well plates. The recovery of HCoV-OC43 from 100% cotton was comparable between PBS and culture media as diluents, whereas recovery was reduced using MRD. Shaking by hand was the most efficient recovery method used, with 98.56% of the inoculum being recovered. The stability of HCoV-OC43 was greatest on polyester, where it remained infectious for at least 6 hours. Investigations into the decontamination of model human coronaviruses under wash parameters are ongoing. Investigations on the survival of coronaviruses is required to evaluate the infection control risk of contaminated textiles and to identify laundering parameters required to adequately decontaminate linen. This study demonstrates that model coronaviruses survive on textiles, indicating that there may be a risk within the healthcare and domestic environments.

Summary HIV-1 spreads between CD4 T cells most efficiently through virus-induced cell-cell contacts. To test whether this process potentiates viral spread by activating signaling pathways, we developed an approach to analyze the phosphoproteome in infected and uninfected mixed-population T cells using differential metabolic labeling and mass spectrometry. We discovered HIV-1-induced activation of signaling networks during viral spread encompassing over 200 cellular proteins. Strikingly, pathways downstream of the T cell receptor were the most significantly activated, despite the absence of canonical antigen-dependent stimulation. The importance of this pathway was demonstrated by the depletion of proteins, and we show that HIV-1 Env-mediated cell-cell contact, the T cell receptor, and the Src kinase Lck were essential for signaling-dependent enhancement of viral dissemination. This study demonstrates that manipulation of signaling at immune cell contacts by HIV-1 is essential for promoting virus replication and defines a paradigm for antigen-independent T cell signaling., Graphical Abstract, Highlights • Unbiased global analysis of T cell signaling changes during HIV-1 cell-cell spread • Experimental system to map dynamic signaling changes in mixed cell populations over time • More than 200 host cell proteins are modified as HIV-1 disseminates between T cells • HIV-1 activates antigen-independent TCR signaling to drive viral spread, HIV-1 rapidly spreads between T cells. Len et al. have developed an approach to interrogate real-time signaling changes in infected and uninfected cells during viral dissemination. They report that HIV-1-induced cell-cell contact activates antigen-independent T cell signaling that is necessary for HIV-1 to spread efficiently between cells.