During a pandemic, nonspecific immunoprophylaxis of
SARS-CoV-2 infection and other acute
respiratory infections (ARI), which can worsen the course of
COVID-19, is increasingly in demand in addition to specific immunization.
BCG vaccine appears to be one of the candidate
immunostimulants in this regard. At the same time, other microbe-derived preparations capable of inducing a state of trained immunity deserve attention. BCG and other bacterial immunostimulatory agents containing a large number of biologically active subunits have long been considered as objects of search for promising pharmacological substances. The review analyzes the linkages between BCG, mycobacterial adjuvants,
bacterial lysates, trained immunity, muramylpeptides (MPs) and NOD2 receptors in light of the choice of a low molecular weight alternative to multicomponent bacterial
immunostimulants for ARI prevention during the
COVID-19 pandemic. The search for key molecules by which bacteria stimulate innate and adaptive immune responses proceeds in a spiral. On different loops of this spiral, MPs have repeatedly reproduced the nonspecific effects of multicomponent bacterial adjuvants,
vaccines and
immunostimulants. MPs and peptidoglycans containing MPs determine the adjuvant properties of the cell walls of mycobacteria and their
peptide-
glycolipid fraction (
wax D). MPs were able to replace Mycobacterium tuberculosis in complete
Freunds adjuvant. MPs determine the NOD2-dependent ability of BCG to induce trained immunity. Probably, MPs provide NOD2-mediated long-term prophylactic action of
bacterial lysates. All of the above has prompted revisiting the previously obtained evidence of the efficacy of
glucosaminylmuramyl dipeptide (GMDP) as a NOD2 agonist in treatment/prevention of
respiratory infections. We speculate here that MPs, in particular GMDP, at rational dosing regimens will be able to reproduce many aspects of the nonspecific effects of BCG and multicomponent bacterial
immunostimulants in preventing ARI during the
COVID-19 pandemic and in the post-pandemic period.