4.8 Article

Niacinamide enhances cathelicidin mediated SARS-CoV-2 membrane disruption

Journal

FRONTIERS IN IMMUNOLOGY
Volume 14, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2023.1255478

Keywords

COVID-19; SARS-CoV-2; antimicrobial peptides; niacinamide; LL37; skin immunity; viral membrane

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The emergence of SARS-CoV-2 variants poses a threat to global vaccination programs, necessitating the exploration of additional strategies for containment. Human cathelicidin (LL37), an antimicrobial peptide, has been found to neutralize multiple strains of SARS-CoV-2 by disrupting the viral membrane. This antiviral activity can be enhanced by niacinamide, and there is an inverse correlation between LL37 levels and COVID-19 disease severity, suggesting its potential as a therapeutic avenue.
The continual emergence of SARS-CoV-2 variants threatens to compromise the effectiveness of worldwide vaccination programs, and highlights the need for complementary strategies for a sustainable containment plan. An effective approach is to mobilize the body's own antimicrobial peptides (AMPs), to combat SARS-CoV-2 infection and propagation. We have found that human cathelicidin (LL37), an AMP found at epithelial barriers as well as in various bodily fluids, has the capacity to neutralise multiple strains of SARS-CoV-2. Biophysical and computational studies indicate that LL37's mechanism of action is through the disruption of the viral membrane. This antiviral activity of LL37 is enhanced by the hydrotropic action of niacinamide, which may increase the bioavailability of the AMP. Interestingly, we observed an inverse correlation between LL37 levels and disease severity of COVID-19 positive patients, suggesting enhancement of AMP response as a potential therapeutic avenue to mitigate disease severity. The combination of niacinamide and LL37 is a potent antiviral formulation that targets viral membranes of various variants and can be an effective strategy to overcome vaccine escape.

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