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Background The COVID-19 pandemic continues to devastate communities all over the world. The aim of this study was to evaluate the efficacy and safety of the test agent as a prophylaxis against SARS-CoV-2 infection in a population of high-risk healthcare workers. Methods The study was a multi-centre, prospective, double blind, randomized, placebo-controlled trial. Key eligibility criteria included absence of significant co-morbidity and no previous SARS-CoV-2 infection or vaccination. Participants were randomised to either the active agent nasal spray or placebo using computer generated random number tables. The nasal spray was administered 3 times daily over a 45 day course. The primary end point was the percentage of subjects who tested positive for IgGS (anti-spike, immunoglobulin G specific to the spike protein of SARS-CoV-2) at day 45. Results Between 16th April 2021 and 26th July 2021, 556 participants were analysed for the primary endpoint (275 Test; 281 Placebo). The test agent significantly reduced SARS-CoV-2 infection compared to placebo [36 cases (13.1%) Vs 97 cases (34.5%); OR 0.29 (95% CI; 0.18-0.45), p < 0.0001]. Fewer clinical symptoms were also seen in the test group [57 cases (17.6%) vs 112 cases (34.6%); OR 0.40, (95% CI; 0.27-0.59), p < 0.0001]. No harmful effects were associated with taking the test agent. Conclusion The test agent significantly reduced SARS-CoV-2 infection in healthcare workers, with 62% fewer infections when compared to placebo. It was found to be safe and well tolerated and offers a novel treatment option for prophylaxis against SARS-CoV-2 infection., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. JAS, LS, AD, KED, SGD, MAM, AM, RM, DR, AJR, and RU are shareholders of Raphael Labs LTD. JS is the managing director of Swales Pharma Consulting providing consulting services for a range of pharmaceutical companies. AJM and AR sit on the advisory board of Raphael labs., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Therapeutic approaches to stimulate regeneration and repair have the potential to transform healthcare and improve outcomes for patients suffering from numerous chronic degenerative diseases. To date most approaches have involved the transplantation of therapeutic cells, and while there have been a small number of clinical approvals, major hurdles exist to the routine adoption of such therapies. In recent years humans and other mammals have been shown to possess a regenerative capacity across multiple tissues and organs, and an innate regenerative and repair response has been shown to be activated in these organs in response to injury. These realisations have inspired a transformative approach in regenerative medicine: the development of new agents to directly target these innate regeneration and repair pathways. In this article we will review the current state of the art in the discovery of small molecule modulators of regeneration and their translation towards therapeutic agents, focussing specifically on the areas of neuroregeneration and cardiac regeneration., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The capacity to harness the properties of pluripotent stem cells has a wide-reaching impact on regenerative medicine, drug discovery, and also basic science. Two recent publications by Ursu et al. and Illich et al. demonstrate that inhibition of a CK1 isoform efficiently induces naive pluripotency in epiblast stem cells., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Screening of our chemical library to discover new molecules exhibiting in vitro activity against the invasion of host cells by Eimeria tenella revealed a lead compound with an IC50 of 15μM. Structure-activity relationship studies were conducted with 34 newly synthesized compounds to identify more active molecules and enhance in vitro activity against the parasite. Four compounds were more effective in inhibiting MDBK cell invasion in vitro than the lead compound., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

An in vitro screening of the anti-apicomplexan activity of 51 compounds, stemming from our chemical library and from chemical synthesis, was performed. As a study model, we used Toxoplasma gondii (T. gondii), expressing β-galactosidase for the colorimetric assessment of drug activity on parasites cultivated in vitro. This approach allowed the validation of a new series of molecules with a biphenylimidazoazine scaffold as inhibitors of T. gondii growth in vitro. Hence, 8 molecules significantly inhibited intracellular replication of T. gondii in vitro, with EC50 < 1 μM, while being non-toxic for human fibroblasts at these concentrations. Most attractive candidates were then selected for further biological investigations on other apicomplexan parasites (Neospora caninum, Besnoitia besnoiti, Eimeria tenella and Plasmodium falciparum). Finally, two compounds were able to inhibit growth of four different apicomplexans with EC50 in the submicromolar to nanomolar range, for each parasite. These data, including the broad anti-parasite spectrum of these inhibitors, define a new generation of potential anti-parasite compounds of wide interest, including for veterinary application. Studies realized on E. tenella suggest that these molecules act during the intracellular development steps of the parasite. Further experiments should be done to identify the molecular target(s) of these compounds., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)