SARS-CoV-2 Protein Structural Molecular Simulation Focused on Variants of Concern/Interest

Our research objective for this submission is to build upon our previously successful drug simulation-based re-purposing research on SARS-CoV-2 enabled by the XSEDE/HPC COVID consortium. Our prior research focused on the alpha variant and resulted into a multi-institution collaboration among ARIScience, the NIH, Johns Hopkins University, Brown University, Oregon Health Sciences University and others. This proposed research extends our prior work into emergent SAR-CoV-2 variants of concern/interest (e.g., Delta and Mu variants). \n \n As before we plan to do this via (a) our novel high performance quasi-quantum simulation platform using FDA-approved compounds against SARS-CoV-2 protein structures and sub-structures – focused on spike protein mutations of variants of concern and variants of interest, (b) epidemiological analysis of discovered candidates via already established access to NIH’s N3C COVID data cohort. Research objective (a) is specifically the subject of this request as it requires significant computational resources.\n \n For the reader’s reference our prior work resulted into three manuscripts, one manuscript directly focused on our simulation and subsequently clinical validation that shows nearly 25% reduction of COVID mortality associated with use of drug interactions we discovered, and two manuscript resulting from exploration ideas from the multi-institution collaboration.\n \n This proposed work is impactful as it will either (a) validate applicability of our findings against SARS-CoV-2 alpha to Delta/Mu/emergent variants or (b) find other drugs with potential clinical impact of SARS-CoV-2