Niacinamide enhances cathelicidin mediated SARS-CoV-2 membrane disruption

Abstract

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.

Mechanistic Insights into the Multiple Functions of Niacinamide: Therapeutic Implications and Cosmeceutical Applications in Functional Skincare Products

“…Studies demonstrated that keratinocytes treated with a niacinamide solution were successfully stimulated to synthesize AMPs in vitro, providing protection against skin infection [68]. Furthermore, there is evidence that niacinamide can potentiate the activity of cathelidicin LL-37 [77,79]. Specifically, due to niacinamide's amphiphilic nature, the molecule modulates the physical properties of the bacterial membrane and increases LL-37 bioavailability [77,79].…”

“…Furthermore, there is evidence that niacinamide can potentiate the activity of cathelidicin LL-37 [77,79]. Specifically, due to niacinamide's amphiphilic nature, the molecule modulates the physical properties of the bacterial membrane and increases LL-37 bioavailability [77,79]. Of note, several studies correlated niacinamide's antimicrobial activity with increased neutrophil activity, demonstrating that niacinamide selectively enhanced the neutrophil killing of Staphylococcus aureus and Citrobacter rodentium [75,77,80].…”

The Potential Use of Vitamin D3 and Phytochemicals for Their Anti-Ageing Effects

“…During viral infections, type-1 interferon (IFN), IFN-α, and IFN-β exert antiviral activity during viral infections, and CAMP/LL-37 exerts antiviral activity as well [43]. Vitamin D3 acts protectively during infections with several viral strains, including hepatitis viruses, the human immunodeficiency virus, and respiratory pathogenic viruses.…”