This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Rima Hajjo
Al-Zaytoonah University of Jordan
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7090-5425
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Declarations:
Declarations
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
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. However, the vaccine may prove ineffective due to rapid changes in viral antigenic determinants. Bacillus Calmette–Guérin (BCG) vaccine has been recognized for its off-target beneficial effects on the immune system, therefore, can be exploited to boast immunity and protect from emerging novel viruses.
Methods: We developed a systems biology workflow capable of identifying small-molecule antiviral drugs and vaccines that can boast immunity and impact a wide variety of viral disease pathways to protect from the fatal consequences of emerging viruses.
Results: We show that BCG affect the production and maturation of naïve T cells, which results in enhanced long-lasting trained innate immune responses to tackle novel viruses. Our workflow identified small-molecule BCG mimics, including antiviral drugs such as raltegravir and lopinavir as high confidence hits. Strikingly, top hits emetine and lopinavir were validated to 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 a protection measure from the lethal consequences of emergent viruses including SARS-CoV-2.
Keywords
BCG vaccine, BCG mimics, COVID-19, innate immunity, SARS-CoV-2, systems biology.
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Rima Hajjo
Al-Zaytoonah University of Jordan
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7090-5425
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
View the published article at Pharmaceutical Research.
Version 1
Posted 14 Jul, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Declarations:
Declarations
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
View the published article at Pharmaceutical Research.
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. However, the vaccine may prove ineffective due to rapid changes in viral antigenic determinants. Bacillus Calmette–Guérin (BCG) vaccine has been recognized for its off-target beneficial effects on the immune system, therefore, can be exploited to boast immunity and protect from emerging novel viruses.
Methods: We developed a systems biology workflow capable of identifying small-molecule antiviral drugs and vaccines that can boast immunity and impact a wide variety of viral disease pathways to protect from the fatal consequences of emerging viruses.
Results: We show that BCG affect the production and maturation of naïve T cells, which results in enhanced long-lasting trained innate immune responses to tackle novel viruses. Our workflow identified small-molecule BCG mimics, including antiviral drugs such as raltegravir and lopinavir as high confidence hits. Strikingly, top hits emetine and lopinavir were validated to 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 a protection measure from the lethal consequences of emergent viruses including SARS-CoV-2.
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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