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Use of Ultra-High-Throughput Screening in Discovery of COVID-19 Virus Structure

One of the top news topics right now concerns the spread of the highly infectious SARS-CoV-2, which is believed to have begun in Wuhan, China and has since infected hundreds of thousands of people worldwide. The virus, which can cause a severe form of pneumonia and lead to acute respiratory distress, currently has no FDA-approved targeted therapeutic or vaccine. For this reason, researchers around the globe are scrambling to understand this novel virus and figure out its potentially targetable vulnerabilities. Speed is of critical importance to ongoing research efforts, given the virus’ rapid spread combined with a massive worldwide shortage of appropriate ventilator equipment.

Thankfully, a recent study from Shanghai demonstrated that researchers have an ally in their work. Ultra-high-throughput plate readers, which include PerkinElmer’s EnVision®, have offered the ability to screen a vast number of potential leads with high detection sensitivity.

COVID-19’s Main Viral Protease Identified as Target

More Than 10,000 Compounds Quickly Assayed

Using computer-aided drug design, the Shanghai-based team identified an inhibitor of Mpro, called N3. They then visualized not only the crystal structure of the SARS-CoV-2 virus, but also N3 in complex with SARS-CoV-2. Virtual and high-throughput screening became invaluable at this point in the study, as the team assayed more than 10,000 compounds to try to identify potential leads. Of these 10,000 compounds, some were drugs already approved for other uses; others were drug candidates being used in clinical trials. Still others were simply known inhibitors of Mpro. Following the high-throughput screening were cell-based assays, which demonstrated that the identified leads had strong anti-viral action. Beyond the identified leads, the Shanghai team’s study also helped the scientific community by publishing their efficient, ultra-high-throughput screening method. With uncertain times ahead, it is reassuring to know that such technology exists and can be used to rapidly respond to serious, evolving health threats.

Sources

  1. https://www.biorxiv.org/content/biorxiv/early/2020/03/10/2020.02.26.964882.full.pdf
  2. https://www.perkinelmer.com/product/envision-hts-plate-reader-2105-0010

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