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10.1073/pnas.2025581118 http://scihub22266oqcxt.onion/10.1073/pnas.2025581118 33906951!8126852!33906951     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=33906951&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Proc+Natl+Acad+Sci+U+S+A 2021 ; 118 (19): ä Nephropedia Template TP {{tp|p=33906951|t=2021. Network medicine framework for identifying drug-repurposing opportunities for COVID-19 |pdf=|usr=}}{{33906951}} gab.com Text Network medicine framework for identifying drug-repurposing opportunities for COVID-19 JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=33906951 #FOAvip The COVID-19 pandemic has highlighted the need to quickly and reliably prioritize clinically approved compounds for their potential effectiveness for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Here, we deployed algorithms relying on artificial intelligence, network diffusion, and network proximity, tasking each of them to rank 6,340 drugs for their expected efficacy against SARS-CoV-2. To test the predictions, we used as ground truth 918 drugs experimentally screened in VeroE6 cells, as well as the list of drugs in clinical trials that capture the medical community's assessment of drugs with potential COVID-19 efficacy. We find that no single predictive algorithm offers consistently reliable outcomes across all datasets and metrics. This outcome prompted us to develop a multimodal technology that fuses the predictions of all algorithms, finding that a consensus among the different predictive methods consistently exceeds the performance of the best individual pipelines. We screened in human cells the top-ranked drugs, obtaining a 62% success rate, in contrast to the 0.8% hit rate of nonguided screenings. Of the six drugs that reduced viral infection, four could be directly repurposed to treat COVID-19, proposing novel treatments for COVID-19. We also found that 76 of the 77 drugs that successfully reduced viral infection do not bind the proteins targeted by SARS-CoV-2, indicating that these network drugs rely on network-based mechanisms that cannot be identified using docking-based strategies. These advances offer a methodological pathway to identify repurposable drugs for future pathogens and neglected diseases underserved by the costs and extended timeline of de novo drug development. Twit Text FOAVip Network medicine framework for identifying drug-repurposing opportunities for COVID-19 ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=33906951 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33906951 #FOAvip English Wikipedia <ref>{{Cite pmid|33906951}}</ref> Network medicine framework for identifying drug-repurposing opportunities for COVID-19 #MMPMID33906951 Morselli Gysi D; do Valle I; Zitnik M; Ameli A; Gan X; Varol O; Ghiassian SD; Patten JJ; Davey RA; Loscalzo J; Barabasi AL Proc Natl Acad Sci U S A 2021[May]; 118 (19): ä PMID33906951show ga The COVID-19 pandemic has highlighted the need to quickly and reliably prioritize clinically approved compounds for their potential effectiveness for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Here, we deployed algorithms relying on artificial intelligence, network diffusion, and network proximity, tasking each of them to rank 6,340 drugs for their expected efficacy against SARS-CoV-2. To test the predictions, we used as ground truth 918 drugs experimentally screened in VeroE6 cells, as well as the list of drugs in clinical trials that capture the medical community's assessment of drugs with potential COVID-19 efficacy. We find that no single predictive algorithm offers consistently reliable outcomes across all datasets and metrics. This outcome prompted us to develop a multimodal technology that fuses the predictions of all algorithms, finding that a consensus among the different predictive methods consistently exceeds the performance of the best individual pipelines. We screened in human cells the top-ranked drugs, obtaining a 62% success rate, in contrast to the 0.8% hit rate of nonguided screenings. Of the six drugs that reduced viral infection, four could be directly repurposed to treat COVID-19, proposing novel treatments for COVID-19. We also found that 76 of the 77 drugs that successfully reduced viral infection do not bind the proteins targeted by SARS-CoV-2, indicating that these network drugs rely on network-based mechanisms that cannot be identified using docking-based strategies. These advances offer a methodological pathway to identify repurposable drugs for future pathogens and neglected diseases underserved by the costs and extended timeline of de novo drug development. |*COVID-19 Drug Treatment[MESH] |Animals[MESH] |Antiviral Agents/administration & dosage/pharmacology/therapeutic use[MESH] |Chlorocebus aethiops[MESH] |Databases, Pharmaceutical[MESH] |Drug Repositioning/*methods[MESH] |Humans[MESH] |Neural Networks, Computer[MESH] |Protein Binding[MESH] |Systems Biology/*methods[MESH] |Vero Cells[MESH]Network medicine framework for identifying drug-repurposing opportunit(epmc).pdf DeepDyve Pubget Overpricing