RESUMO
The COVID-19 pandemic is a stark reminder that a barren global antiviral pipeline has grave humanitarian consequences. Future pandemics could be prevented by accessible, easily deployable broad-spectrum oral antivirals and open knowledge bases that derisk and accelerate novel antiviral discovery and development. Here, we report the results of the COVID Moonshot, a fully open-science structure-enabled drug discovery campaign targeting the SARS-CoV-2 main protease. We discovered a novel chemical scaffold that is differentiated from current clinical candidates in terms of toxicity, resistance, and pharmacokinetics liabilities, and developed it into noncovalent orally-bioavailable nanomolar inhibitors with clinical potential. Our approach leveraged crowdsourcing, high-throughput structural biology, machine learning, and exascale molecular simulations. In the process, we generated a detailed map of the structural plasticity of the main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. In a first for a structure-based drug discovery campaign, all compound designs (>18,000 designs), crystallographic data (>500 ligand-bound X-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2,400 compounds) for this campaign were shared rapidly and openly, creating a rich open and IP-free knowledgebase for future anti-coronavirus drug discovery.
RESUMO
We analyze the temporal evolution of accumulated hospitalization cases due to COVID-19 in Belgium. The increase of hospitalization cases is consistent with an initial exponential phase, and a subsequent power law growth. For the latter, we estimate a power law exponent of {approx} 2.2, which is consistent with growth kinetics of COVID-19 in China and indicative of the underlying small world network structure of the epidemic. Finally, we fit an SIR-X model to the experimental data and estimate the effect of containment policies in comparison to their effect in China. This model suggests that the base reproduction rate has been significantly reduced, but that the number of susceptible individuals that is isolated from infection is very small. Based on the SIR-X model fit, we analyze the COVID-19 mortality and the number of patients requiring ICU treatment over time.