Site mapping and small molecule blind docking reveal a possible target site on the SARS-CoV-2 main protease dimer interface
Julia Liang, Chris Karagiannis, Eleni Pitsillou, Kevion K Darmawan, Ken Ng, Andrew Hung, Tom C Karagiannis
Computational Biology and Chemistry | ELSEVIER SCI LTD | Published : 2020
The SARS-CoV-2 virus is causing COVID-19 resulting in an ongoing pandemic with serious health, social, and economic implications. Much research is focused in repurposing or identifying new small molecules which may interact with viral or host-cell molecular targets. An important SARS-CoV-2 target is the main protease (Mpro), and the peptidomimetic α-ketoamides represent prototypical experimental inhibitors. The protease is characterised by the dimerization of two monomers each which contains the catalytic dyad defined by Cys145 and His41 residues (active site). Dimerization yields the functional homodimer. Here, our aim was to investigate small molecules, including lopinavir and ritonavir, α..View full abstract
We would like to acknowledge intellectual and financial support by McCord Research (Iowa, USA). JL and KKD are supported by an Australian Government Research Training Program Scholarship. We are indebted to Alfonso Perez Escudero and the team at Crowdfightcovid for enabling access to supercomputing facilities and to Matthew Gasperetti and the team at Hypernet Labs (Galileo), for enabling cloud computing for this project. We thank the National Computing Infrastructure (NCI), and in particular the Pawsey Supercomputing Centre (which provided specific time for COVID-19 related work on the Topaz GPU cluster), in Australia (funded by the Australian Government). We are grateful for the expert support provided by Marco De La Pierre (supercomputing application specialist). Further, we thank the Spartan High Performance Computing service (University of Melbourne), and the Partnership for Advanced Computing in Europe (PRACE) for awarding the access to Piz Daint, hosted at the Swiss National Supercomputing Centre (CSCS), Switzerland. All data is available in the main text or supplementary materials.