Computational blind challenges offer critical, unbiased opportunities to assess and accelerate scientific progress, as demonstrated by a breadth of breakthroughs over the past decade. We report the outcomes and key insights from an open science community blind challenge focused on computational methods in drug discovery, using lead optimization data from the AI-driven Structure-enabled Antiviral Platform Discovery Consortium's pan-coronavirus antiviral discovery program, in partnership with Polaris and the OpenADMET project. This collaborative initiative invited global participants from both academia and industry to develop and apply computational methods to predict the biochemical potency and crystallographic ligand poses of small molecules against key coronavirus targets, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) main protease (Mpro), as well as multiple ADMET assay end points, using previously undisclosed comprehensive experimental drug discovery data sets as benchmarks. By evaluating submissions across multiple tasks and compounds, we established performance leaderboards and conducted meta-analyses to assess methodological strengths, common pitfalls, and areas for improvement. This analysis provides a foundation for best practices in real-world machine learning evaluation, grounded in community-driven benchmarking. We also highlight how next-generation platforms, such as Polaris, enable rigorous challenge design, embedded evaluation frameworks, and broad community engagement. This paper reports the collective findings of the challenge, offering a high-level overview of the data, evaluation infrastructure, and top-performing strategies. We further provide context and support for the accompanying papers authored by the challenge participants in this special issue, which explore individual approaches in greater depth. Together, these contributions aim to advance reproducible, trustworthy, and high-impact computational methods in drug discovery, and to explore best practices and pitfalls in future blind challenge design and execution, including planned initiatives for the OpenADMET project.