1 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. Currently there are no approved drugs to treat COVID-19, and new vaccine development is expected to take at least 12-18 months, with growing fears of possible failure associated with rapid changes in viral antigenic determinants. Additionally, the highly specific virus-neutralizing antibodies in recovered patients may be short lived and ineffective in preventing the disease caused by the emerging variable strains of the virus. With these uncertainties regarding an eminent specific SARS-CoV-2 vaccine, we should start thinking about alternatives, such as exploiting the unique capabilities of our innate immune system.
Recent immuno-oncology success stories indicate that the best cancer-fighting strategies results from unleashing the patients’ immune power. And there is an increased awareness that harnessing innate immune responses, opens up new possibilities for long-term, multifaceted tumor control and infectious disease prevention. Therefore, next 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.
Accumulating evidence from the biomedical literature indicates that SARS-CoV-mediated pathology, a very similar pathology to SARS-CoV-2, was mainly caused by ineffective innate immune responses, associated with a severe reduction in the number of T cells in the blood. Recent evidence indicated that SARS-CoV-2 and Mycobacterium tuberculosis(Mtb ) share unique similarities in terms of host protein interaction partners, and both pathogens infect lung tissues. On the other hand, old ‘polypharmacological vaccines’, such as the BCG vaccine for tuberculosis (TB), has shown promising therapeutic effects on a wide range of infectious and non-infectious diseases including bladder cancer. Studies showed that BCG’s polypharmacological effects were not limited to memory T cell immunity, but promoted strong, beneficial, and long-lasting effects on innate immunity. The WHO has also recognized these beneficial ‘off-target’ effects of BCG, calling for a further investigation to repurpose for other orphan life-threatening diseases. There are 35 clinical trials reported on clinicaltrials.gov, testing BCG for non-TB conditions including COVID-19. Additionally, few recent peer-reviewed reports have pointed to an epidemiological relationship between BCG and COVID-19 without providing substantial evidence. Therefore, the results of the randomized clinical trials (RCTs) will provide more clues soon.
Herein, we describe a unique drug and vaccine repurposing workflow, and list high confidence proteins and pharmacological classes of compounds, that work as BCG mimics on the systems level by inducing beneficial long lasting trained immune response. Thus, BCG mimics can be used as alternatives to BCG in protecting from COVID-19 and other emergent infectious diseases, or as treatments for bladder cancer and other tumors.