A Systems Biology Workflow for Drug and Vaccine Repurposing: Identifying
Small-molecule BCG Mimics to Prevent COVID-19 Mortality
Abstract
Background. Coronavirus disease 2019 (COVID-19) is expected to continue
to cause worldwide fatalities until the World population develops ‘herd
immunity’, or until a vaccine is developed and used as a prevention.
However, the vaccine may prove ineffective due to rapid changes in viral
antigenic determinants. Bacillus Calmette–Guérin (BCG) vaccine has been
recognized for its beneficial effects on the immune system, and it is
currently in being tested in clinical trials for COVID-19. However, BCG
shortages may affect clinical decisions regarding the prioritization of
BCG to protect from viral infections, hence, small-molecule BCG-mimics
will be valuable alternatives. Methods. We developed and applied a
systems biology workflow capable of identifying antiviral drugs and
vaccines that can boast immunity and impact viral disease pathways to
prevent the fatal consequences of COVID-19. Results. Our results
indicate that BCG and small-molecule BCG-mimics affect the production
and maturation of naïve T cells, which results in enhanced long-lasting
innate immune responses to tackle novel viruses. Our workflow identified
several antiviral drugs including raltegravir and lopinavir as high
confidence BCG mimics. Top hits including emetine and lopinavir were
validated to inhibit the growth of novel coronavirus SARS-CoV-2 in
vitro. Conclusions. Herein, we provide systems biology support for using
BCG as a protection measure from the lethal consequences of emergent
viruses including SARS-CoV-2. We also provide systems biology evidence
that certain small molecule drugs could mimic the effects of BCG and
serve as alternatives to BCG.