The COVID-19 pandemic is the most serious global health crisis in recent history with over 140,000 deaths in the UK and over 5 million deaths worldwide. Despite extensive vaccination programs, the virus remains transmissible with hospitalisation and mortality remaining high, both in the UK and globally. Infex Therapeutics, in partnership with the University of Liverpool and the Liverpool School of Tropical Medicine, and supported by the Medicines Discovery Catapult, is developing a novel series of drugs to treat coronavirus, including SARS-CoV-2, the cause of the global COVID-19 pandemic. These new drugs work by targeting a key protease essential for viral replication. These inhibitors will help meet a desperate clinical need for novel anti-viral agents which are effective in treating breakthrough cases, unvaccinated and high-risk patients such as those undergoing anti-cancer treatments, leading to reduced hospitalisation and pressure on healthcare systems, and lower death rates. The compounds have potential to treat future SARS-CoV-2 variants and may have utility for use in predicted future pandemics due to the highly conserved nature of the target across different coronaviruses. The objective for this grant is to develop existing hits through lead optimisation to generate advanced drug-like leads, which display in vivo proof of concept in efficacy models and have high potential for preclinical candidate nomination and onwards development towards a safe and effective treatment. This will be achieved by applying a clearly-identified lead-optimisation program including medicinal chemistry, enzymology, virology, safety profiling and efficacy assessment. An innovative airway organoid model using human lung cells will be developed and utilised to aid the translation of preclinical data into clinical trials and will provide broader utility across the industry.

Infections are so common that they are an ever-present risk to the public. Fighting such infections is becoming continually more difficult as the resistance to antibiotics increases. For example, Hospital Acquired Infections - HAIs - increase treatment times, and in extreme cases lead to the death of a patient (an estimated 3.5% of patients who acquire a HAI are reported to die from their infection ~28,000/year in England). Furthermore, the costs incurred to manage a patient who acquires an HAI is around three times higher than that of managing a patient without a HAI. In England, the cost of treating patients infected whilst they are in a hospital is £2.7 billion p.a. and accounts for 7.1 million occupied bed days (corresponding to 21% of the annual number of all bed days across NHS hospitals in England) and 79,700 days of absenteeism among front-line health care professionals. To put the 7.1 million occupied hospital bed days attributable to HAIs into perspective, 5.3 million bed days were occupied by cancer patients in England in 2014; Lung disease in the UK was associated with an estimated 6.1 million occupied bed days in 2011 (BMJ Open 2020;10:e033367\. doi: 10.1136/bmjopen-2019-033367). Typically, the microbes and viral strains that cause such ill health are transmitted by a number of means, most of which originate from contact with a contaminated surface. It is possible to apply various antimicrobial treatments to surfaces and materials, however these are usually applied during the manufacturing stage and have a lower level of performance. Vigorous cleaning of surfaces has varying effectiveness and the chemicals used are damaging to the environment. The project will investigate the feasibility of creating a highly antimicrobial surface that can be applied to the existing built environment with relative ease and reduce the need for surface cleaning. If this can be successfully realised then there will be significant clinical and economic benefits which would accrue from a reduction of the impact that HAIs impose on patients, the NHS and society as a whole.

More than 350,000 people suffer from sepsis in the UK annually, leading to 52,000 deaths. Rapid diagnosis is imperative to enable timely administration of interventional antibiotic treatment, however current methods are insufficient to empower clinicians to act within the critical first hour of admission. Early antibiotic therapy is vital to clinical outcomes, with the risk of septic-shock patient mortality increasing by 7.6% with a delay of every 1 hour in antibiotic administration. As recognised by the UK Government and World Health Organisation objectives, there is an urgent unmet clinical need to develop a simple, rapid and accurate test for sepsis, to facilitate fast intervention for patients with bacterial sepsis. Our technology measures levels of the sepsis-specific CRP-VLDL complex biomarker within a handheld, near-patient point-of-care rapid diagnostic, which seamlessly incorporates into the current clinical care pathway.

Society requires new solutions to reduce the probability of COVID-19 cross-infection as people resume their daily lives. However, common touch surfaces have been shown to contain significant viral and microbial contamination. The SARS-CoV-2 virus can be present on plastic and glass surfaces for several days and multiple users of the same touch surfaces creates a continuous biological load that leads to cross-contamination, despite periodic cleaning. Studies have shown that touch screens of mobile phones belonging to medical staff in COVID-19 wards have a \>80% chance of containing the SARS-CoV-2 virus. It is almost certain that people with COVID-19 will have a highly contaminated mobile phone screens. If they then use public transport ticketing machines, the contamination will pass to that surface, as is the case with other forms of touch screen. A new form of transparent coating has been developed using vacuum coating that is extremely biocidal. These new anti-viral coatings will be tested on ticket machines used widely in transport, and thus break chains of transmission arising from numerous people touching the same surface.

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