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.

中文翻译：

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药物和疫苗再利用的系统生物学工作流程：识别小分子 BCG 模拟物以减少或预防 COVID-19 死亡率

目的

预计 2019 年冠状病毒病 (COVID-19) 将继续在世界范围内造成死亡，直到世界人口形成“群体免疫”，或者直到开发出疫苗并用于预防为止。与此同时，迫切需要寻找替代的抗病毒防御手段。卡介苗 (BCG) 疫苗因其对免疫系统的脱靶有益作用而被认可，可用于增强免疫力并预防新出现的新型病毒。

方法

我们开发并采用了系统生物学工作流程，能够识别小分子抗病毒药物和疫苗，这些药物和疫苗具有免疫力并影响多种病毒性疾病途径，以防止新兴病毒的致命后果。

结果

我们的分析表明，BCG 疫苗会影响初始 T 细胞的产生和成熟，从而增强、持久的训练有素的先天免疫反应，从而提供针对新型病毒的保护。我们已经确定了小分子卡介苗模拟物，包括拉替拉韦和洛匹那韦等抗病毒药物，这些药物的可信度很高。引人注目的是，我们的热门药物依米丁和洛匹那韦最近的实验结果独立验证了这些化合物在体外抑制 SARS-CoV-2 的生长。

结论

我们的结果为使用卡介苗和小分子卡介苗模拟物作为针对包括 SARS-CoV-2 在内的新出现病毒的假定疫苗和候选药物提供了系统生物学支持。