Abstract

USEFUL ROLE OF NON-SELECTIVE P38 MAPK- NF-KB SIGNALING PATHWAY INHIBITORS THAT MAY PREVENT COVID-19 MORBIDITY AND SARS-COV2 MUTATIONS: A PILOT REPORT AND REVIEW

S. E. Oriaifo*, D. O. Oriaifo, R. A. Oriaifo, A. Asalu and B. Adegboro

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Abstract

The World Health Organization (WHO) has not declared the COVID- 19 pandemic over, a disease now associated with approximately 226 million cases with over 4.6 million deaths worldwide (JHU). The number of doses of vaccines administered stand at 5.79 billion offering coverage to 37.7% of world’s population, not enough to guarantee herd immunity (Bloomberg.com). In spite of the success of vaccination efforts, for the disease may now be termed a “pandemic of the unvaccinated”, new SARS-CoV2 variants not fully sensitive to current vaccines and able to infect people becloud any reasonable prediction. Easily available approved drugs that may attenuate COVID-19 symptoms and enhance vaccine efficacy by repressing SARS-CoV2 replication/mutation may be worthwhile. Mechanistically, inhibitors of NF-kB which also inhibit mast cell activation may prevent both type 2 diabetes and COVID-19 as well as their related complications. The non-selective p38 MAPK-NF-kB signaling pathway inhibitors metformin, nifedipine, loratadine and doxazosin display overlapping anti-viral actions against SARS-CoV2 and their judicious use may be beneficial against COVID-19. In the present report, combinatorial use of metformin + nifedipine, metformin + loratadine, metformin + 81 mg aspirin and metformin + doxazosin was significantly more effective (P < 0.05) in decreasing BMI and glucose levels, attenuating occurrence of new infections, preventing Long - COVID and abating complications of vaccinations when compared to metformin alone or to controls. Adjunctive use of these known NF-kB inhibitors may be a compelling need in the present pandemic and their wider trial is indicated.

Keywords: SARS-CoV2; COVID-19, Metformin, Nifedipine, Loratadine, 81 mg Aspirin, Doxazosin, NF-kB inhibitor.