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Nuclear factor kappa B (NFkB) presents a promising therapeutic opportunity to mitigate COVID-19-induced cytokine storm and reduce the risk of severe morbidity and mortality resulting from the disease. However, the effective clinical application of NFkB modulators in COVID-19 is hampered by a number of factors that must be taken into consideration. This paper therefore explored the modulation of the NFB pathway as a potential strategy to mitigate the severe morbidity and mortality caused by COVID-19. The paper also discusses the factors that form the barrier, and it offers potential solutions to the various limitations that may impede the clinical use of NFkB modulators against COVID-19. This paper revealed and identified three key potential solutions for the future clinical use of NFkB modulators against COVID-19. These solutions are pulmonary tissue-specific NFkB blockade, agents that target common regulatory proteins of both canonical and non-canonical NFkB pathways, and monitoring clinical indicators of hyperinflammation and cytokine storm in COVID-19 prior to using NFkB modulators.<\/jats:p>","DOI":"10.4081\/jphia.2022.1679","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T13:14:22Z","timestamp":1665580462000},"page":"10","source":"Crossref","is-referenced-by-count":5,"title":["Exploring NFkB pathway as a potent strategy to mitigate COVID-19 severe morbidity and mortality"],"prefix":"10.4102","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0001-5408","authenticated-orcid":false,"given":"Mubarak","family":"Muhammad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tasneem M.","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sani S.","family":"Baba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustapha I.","family":"Radda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mubarak M.","family":"Mutawakkil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Majida A.","family":"Musa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sazaly","family":"AbuBakar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih Keng","family":"Loong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim","family":"Yusuf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2580","published-online":{"date-parts":[[2022,9,7]]},"reference":[{"key":"3424","doi-asserted-by":"crossref","unstructured":"Berg MK, Yu Q, Salvador CE, et al. 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