Related Experiment Video
Updated: Dec 6, 2025
Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
Published on: December 11, 2016
A Systems Biology Workflow for Drug and Vaccine Repurposing: Identifying Small-Molecule BCG Mimics to Reduce or
Rima Hajjo1, Alexander Tropsha2
1Department of Pharmacy - Computational Chemical Biology, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan. rhajjo@gmail.com.
Purpose:
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. Meanwhile, there is an urgent need to identify alternative means of antiviral defense. Bacillus Calmette-Guérin (BCG) vaccine that has been recognized for its off-target beneficial effects on the immune system can be exploited to boast immunity and protect from emerging novel viruses.
Methods:
We developed and employed a systems biology workflow capable of identifying small-molecule antiviral drugs and vaccines that can boast immunity and affect a wide variety of viral disease pathways to protect from the fatal consequences of emerging viruses.
Results:
Our analysis demonstrates that BCG vaccine affects the production and maturation of naïve T cells resulting in enhanced, long-lasting trained innate immune responses that can provide protection against novel viruses. We have identified small-molecule BCG mimics, including antiviral drugs such as raltegravir and lopinavir as high confidence hits. Strikingly, our top hits emetine and lopinavir were independently validated by recent experimental findings that these compounds inhibit the growth of SARS-CoV-2 in vitro.
Conclusions:
Our results provide systems biology support for using BCG and small-molecule BCG mimics as putative vaccine and drug candidates against emergent viruses including SARS-CoV-2.
Insights
The Bacillus Calmette-Guérin (BCG) vaccine enhances trained innate immunity, offering protection against novel viruses. Small-molecule mimics of BCG, including antiviral drugs like emetine and lopinavir, show promise for treating emerging viral infections.
Area of Science:
- Immunology
- Virology
- Systems Biology
- Pharmacology
Background:
- Emerging viruses like SARS-CoV-2 pose a significant global health threat.
- The development of herd immunity or effective vaccines is crucial for controlling pandemics.
- There is an urgent need for alternative antiviral defense strategies.
Purpose of the Study:
- To identify novel antiviral drugs and vaccines using a systems biology approach.
- To explore the potential of the Bacillus Calmette-Guérin (BCG) vaccine in boosting immunity against emerging viruses.
- To discover small-molecule mimics of BCG with antiviral properties.
Main Methods:
- Development and application of a systems biology workflow.
- Identification of small molecules affecting viral disease pathways.
- Analysis of BCG vaccine's impact on immune responses.
Main Results:
- BCG vaccine enhances naive T cell production and maturation, leading to trained innate immunity.
- Small-molecule BCG mimics, including raltegravir and lopinavir, were identified as high-confidence hits.
- Emetine and lopinavir demonstrated in vitro inhibition of SARS-CoV-2, validating their antiviral potential.
Conclusions:
- Systems biology supports BCG and its mimics as potential vaccine and drug candidates against emergent viruses.
- BCG-mimicking small molecules offer a promising avenue for antiviral drug development.
- This research provides a foundation for developing new strategies against SARS-CoV-2 and other novel viruses.
Related Concept Videos
01:29Microorganisms in Medicine and Therapeutics
01:28Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
01:26Drug Discovery: Overview