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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. 

A global international initiative, such as the Earth BioGenome Project (EBP), requires both agreement and coordination on standards to ensure that the collective effort generates rapid progress toward its goals. To this end, the EBP initiated five technical standards committees comprising volunteer members from the global genomics scientific community: Sample Collection and Processing, Sequencing and Assembly, Annotation, Analysis, and IT and Informatics. The current versions of the resulting standards documents are available on the EBP website, with the recognition that opportunities, technologies, and challenges may improve or change in the future, requiring flexibility for the EBP to meet its goals. Here, we describe some highlights from the proposed standards, and areas where additional challenges will need to be met.