Targeting Spike-ACE2 Interaction Using Reinforcement Learning Guided Virtual Screening
Amit Michaeli
Head of Research and Director, Pepticom
The ongoing COVID19 pandemic, caused by the SARS-CoV-2 virus, presents a global drug discovery challenge, with over 2 million deaths recorded by January 2021. Similar to the 2003 SARS epidemic, viral host cell entry was shown to be mediated by the human angiotensin-converting enzyme 2 (ACE2) receptor binding a viral spike protein. Concentrated scientific efforts, yielded structures of the SARS-CoV-2 spike/ACE2 complex deposited in the Protein Data Bank (www.pdb.org) by February 2020, allowing the early application of structure-based drug design. The relatively flat spike/ACE2 interface and the conformational shifts of the Receptor Binding Domain (RBD) allow the application of macrocycle discovery for both direct and allosteric inhibition strategies. In this talk I will review Pepticom’s application of its discovery platform in the two different targeting strategies for the spike/ACE2 complex and share early results for each strategy.