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Drug repositioning candidates identified using in-silico quasi-quantum molecular simulation demonstrate reduced COVID-19 mortality in 1.5M patient records
Preprint
in English
| medRxiv
| ID: ppmedrxiv-21254110
ABSTRACT
BackgroundDrug repositioning is a key component of COVID-19 pandemic response, through identification of existing drugs that can effectively disrupt COVID-19 disease processes, contributing valuable insights into disease pathways. Traditional non in silico drug repositioning approaches take substantial time and cost to discover effect and, crucially, to validate repositioned effects. MethodsUsing a novel in-silico quasi-quantum molecular simulation platform that analyzes energies and electron densities of both target proteins and candidate interruption compounds on High Performance Computing (HPC), we identified a list of FDA-approved compounds with potential to interrupt specific SARS-CoV-2 proteins. Subsequently we used 1.5M patient records from the National COVID Cohort Collaborative to create matched cohorts to refine our in-silico hits to those candidates that show statistically significant clinical effect. ResultsWe identified four drugs, Metformin, Triamcinolone, Amoxicillin and Hydrochlorothiazide, that were associated with reduced mortality by 27%, 26%, 26%, and 23%, respectively, in COVID-19 patients. ConclusionsTogether, these findings provide support to our hypothesis that in-silico simulation of active compounds against SARS-CoV-2 proteins followed by statistical analysis of electronic health data results in effective therapeutics identification.
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Full text:
Available
Collection:
Preprints
Database:
medRxiv
Type of study:
Cohort_studies
/
Observational study
/
Prognostic study
Language:
English
Year:
2021
Document type:
Preprint