Abstract

PurposeCoronavirus 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.MethodsWe 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.ResultsOur 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (10.1007/s11095-020-02930-9) contains supplementary material, which is available to authorized users.

Highlights

  • Few months after the declaration of COVID-19 pandemic by the World Health Organization (WHO), the disease-causing virus is still sweeping the globe, causing more fatalities, failing health care systems, and resulting in severe economic losses

  • Our results provide systems biology support for using Bacillus Calmette–Guérin (BCG) and small-molecule BCG mimics as putative vaccine and drug candidates against emergent viruses including SARS-CoV-2

  • A consensus gene signature for BCG vaccine was derived from gene expression profiles in peripheral blood mononuclear cells (PBMCs) in response to a BCG challenge test reported by Matsumiya et al [76], GSE58636 dataset on NCBI Gene Expression Omnibus (GEO) [27]

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Summary

Introduction

Few months after the declaration of COVID-19 pandemic by the World Health Organization (WHO), the disease-causing virus is still sweeping the globe, causing more fatalities, failing health care systems, and resulting in severe economic losses. The highly specific virusneutralizing antibodies in recovered patients may be short lived and ineffective in preventing the disease caused by the emerging variable strains of the virus [4]. With these uncertainties regarding an eminent specific SARS-CoV-2 vaccine, there is a need to search for current alternatives, such as agents that can stimulate or emulate the unique capabilities of our innate immune system. Generation antiviral vaccines should be capable of boosting innate immune responses to tackle a wide range of novel pathogens very early after exposure, as single treatments or adjuvants to traditional vaccines targeting the adaptive immune system

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