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.