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

The Year 1999: An Attempt at Political Forecasting

Political events will to a considerable degree predominate over economics in 1999, although the economic crisis, in turn, will affect the course of the political election races, imposing on them certain constraints beyond which no political force will be able to go. If we view the crisis of 1998-99 as a systemic (and cyclical) one, it can be said that unless a number of political and governmental problems are solved, it will be impossible to overcome the economic crisis, and that the state of the Russian economy will impede the adoption of various political and governmental decisions.

Reducing the complexity of financial networks using network embeddings

Abstract Accounting scandals like Enron (2001) and Petrobas (2014) remind us that untrustworthy financial information has an adverse effect on the stability of the economy and can ultimately be a source of systemic risk. This financial information is derived from processes and their related monetary flows within a business. But as the flows are becoming larger and more complex, it becomes increasingly difficult to distill the primary processes for large amounts of transaction data. However, by extracting the primary processes we will be able to detect possible inconsistencies in the information efficiently. We use recent advances in network embedding techniques that have demonstrated promising results regarding node classification problems in domains like biology and sociology. We learned a useful continuous vector representation of the nodes in the network which can be used for the clustering task, such that the clusters represent the meaningful primary processes. The results show that we can extract the relevant primary processes which are similar to the created clusters by a financial expert. Moreover, we construct better predictive models using the flows from the extracted primary processes which can be used to detect inconsistencies. Our work will pave the way towards a more modern technology and data-driven financial audit discipline

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