A community effort in SARS-CoV-2 drug discovery.

peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric

Photonic Lab-on-a-Chip analytical systems for nuclear applications: optical performance and UV–Vis–IR material characterization after chemical exposure and gamma irradiation

International audienceThe use of microfluidics technology and the miniaturization of analytical techniques is of high interest for the chemical and nuclear industries. In the latter, the reduction of effluents deriving from actinides concentration monitoring along R&D and pilot-scale purification processes is a permanent concern. Indeed, the extremely harsh operation conditions limit the implementation of standard analytical techniques and methodologies, and in this regard, the use of spectrophotometric techniques for effluents characterization becomes advantageous in terms of robustness, implementation and sensitivity at the microfluidic scale. In this work, we report a study of the effect of exposure to different chemicals used in hydrometallurgical processes, and to gamma radiation typical of the Plutonium and Uranium Refining by Extraction process, on the optical and structural properties of different polymeric materials commonly used for the fabrication of microfluidic and optofluidic systems. This study shows that low-cost castable and/or engravable materials (e.g. polydimethylsiloxane and poly-methyl methacrylate) are ideal for the study and development of Photonic Lab on a Chip systems that will be used in a nuclear environment

A community effort to discover small molecule SARS-CoV-2 inhibitors

The COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of a community effort, the “Billion molecules against Covid-19 challenge”, to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 potentially active molecules, which were subsequently ranked to find ‘consensus compounds’. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (Nsp12 domain), and (alpha) spike protein S. Overall, 27 potential inhibitors were experimentally confirmed by binding-, cleavage-, and/or viral suppression assays and are presented here. All results are freely available and can be taken further downstream without IP restrictions. Overall, we show the effectiveness of computational techniques, community efforts, and communication across research fields (i.e., protein expression and crystallography, in silico modeling, synthesis and biological assays) to accelerate the early phases of drug discovery