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Niacinamide enhances cathelicidin mediated SARS-CoV-2 membrane disruption

View ORCID ProfileTanay Bhatt, View ORCID ProfileSneha Uday Khedkar, View ORCID ProfileBinita Dam, View ORCID ProfileSahil Lall, Subhashini Pandey, View ORCID ProfileSunny Kataria, Paul M Dias, Morris Waskar, Janhavi Raut, View ORCID ProfileVaradharajan Sundaramurthy, View ORCID ProfilePraveen Kumar Vemula, Naresh Ghatlia, Amitabha Majumdar, View ORCID ProfileColin Jamora
doi: https://doi.org/10.1101/2022.08.26.505399
Tanay Bhatt
1IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, Karnataka 560065
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  • ORCID record for Tanay Bhatt
Sneha Uday Khedkar
1IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, Karnataka 560065
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Binita Dam
1IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, Karnataka 560065
2Department of Biological Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka 576104
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Sahil Lall
3National Centre for Biological Sciences (TIFR), Bangalore, Karnataka 560065
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Subhashini Pandey
4Integrative Chemical Biology, Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, Karnataka 560065
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Sunny Kataria
1IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, Karnataka 560065
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Paul M Dias
5Unilever R&D Bangalore, Karnataka 560066
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Morris Waskar
5Unilever R&D Bangalore, Karnataka 560066
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Janhavi Raut
5Unilever R&D Bangalore, Karnataka 560066
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Varadharajan Sundaramurthy
3National Centre for Biological Sciences (TIFR), Bangalore, Karnataka 560065
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  • ORCID record for Varadharajan Sundaramurthy
Praveen Kumar Vemula
4Integrative Chemical Biology, Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, Karnataka 560065
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Naresh Ghatlia
6Unilever R&D Trumbull, Connecticut 06611
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Amitabha Majumdar
5Unilever R&D Bangalore, Karnataka 560066
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  • For correspondence: amitabha.majumdar@unilever.com colinj@instem.res.in
Colin Jamora
1IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, Karnataka 560065
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  • For correspondence: amitabha.majumdar@unilever.com colinj@instem.res.in
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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 inverse correlation between LL37 levels and disease severity of COVID-19 positive patients, suggesting enhancement of AMP response as an interesting 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 potentially overcome vaccine escape.

Competing Interest Statement

PMD, JR, MW, NG, and AM are employees of Unilever R&D

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 26, 2022.
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Niacinamide enhances cathelicidin mediated SARS-CoV-2 membrane disruption
Tanay Bhatt, Sneha Uday Khedkar, Binita Dam, Sahil Lall, Subhashini Pandey, Sunny Kataria, Paul M Dias, Morris Waskar, Janhavi Raut, Varadharajan Sundaramurthy, Praveen Kumar Vemula, Naresh Ghatlia, Amitabha Majumdar, Colin Jamora
bioRxiv 2022.08.26.505399; doi: https://doi.org/10.1101/2022.08.26.505399
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Niacinamide enhances cathelicidin mediated SARS-CoV-2 membrane disruption
Tanay Bhatt, Sneha Uday Khedkar, Binita Dam, Sahil Lall, Subhashini Pandey, Sunny Kataria, Paul M Dias, Morris Waskar, Janhavi Raut, Varadharajan Sundaramurthy, Praveen Kumar Vemula, Naresh Ghatlia, Amitabha Majumdar, Colin Jamora
bioRxiv 2022.08.26.505399; doi: https://doi.org/10.1101/2022.08.26.505399

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