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Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms

Research output: Contribution to Journal/Magazine › Journal article › peer-review

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Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms. / Hall, Steven R; Rasmussen, Sean A; Crittenden, Edouard et al.
In: Nature Communications, Vol. 14, No. 1, 7812, 14.12.2023, p. 1-15.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Hall, SR, Rasmussen, SA, Crittenden, E, Dawson, CA, Bartlett, KE, Westhorpe, AP, Albulescu, L-O, Kool, J, Gutiérrez, JM & Casewell, NR 2023, 'Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms', Nature Communications, vol. 14, no. 1, 7812, pp. 1-15. https://doi.org/10.1038/s41467-023-43510-w

APA

Hall, S. R., Rasmussen, S. A., Crittenden, E., Dawson, C. A., Bartlett, K. E., Westhorpe, A. P., Albulescu, L-O., Kool, J., Gutiérrez, J. M., & Casewell, N. R. (2023). Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms. Nature Communications, 14(1), 1-15. Article 7812. https://doi.org/10.1038/s41467-023-43510-w

Vancouver

Hall SR, Rasmussen SA, Crittenden E, Dawson CA, Bartlett KE, Westhorpe AP et al. Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms. Nature Communications. 2023 Dec 14;14(1):1-15. 7812. doi: 10.1038/s41467-023-43510-w

Author

Hall, Steven R ; Rasmussen, Sean A ; Crittenden, Edouard et al. / Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms. In: Nature Communications. 2023 ; Vol. 14, No. 1. pp. 1-15.

Bibtex

@article{2f3a6bd6c696490cb64bc3bc49d2afee,
title = "Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms",
abstract = "Morbidity from snakebite envenoming affects approximately 400,000 people annually. Tissue damage at the bite-site often leaves victims with catastrophic life-long injuries and is largely untreatable by current antivenoms. Repurposed small molecule drugs that inhibit specific snake venom toxins show considerable promise for tackling this neglected tropical disease. Using human skin cell assays as an initial model for snakebite-induced dermonecrosis, we show that the drugs 2,3-dimercapto-1-propanesulfonic acid (DMPS), marimastat, and varespladib, alone or in combination, inhibit the cytotoxicity of a broad range of medically important snake venoms. Thereafter, using preclinical mouse models of dermonecrosis, we demonstrate that the dual therapeutic combinations of DMPS or marimastat with varespladib significantly inhibit the dermonecrotic activity of geographically distinct and medically important snake venoms, even when the drug combinations are delivered one hour after envenoming. These findings strongly support the future translation of repurposed drug combinations as broad-spectrum therapeutics for preventing morbidity caused by snakebite.",
keywords = "Mice, Humans, Animals, Snake Bites/drug therapy, Snake Venoms/toxicity, Drug Combinations",
author = "Hall, {Steven R} and Rasmussen, {Sean A} and Edouard Crittenden and Dawson, {Charlotte A} and Bartlett, {Keirah E} and Westhorpe, {Adam P} and Laura-Oana Albulescu and Jeroen Kool and Guti{\'e}rrez, {Jos{\'e} Mar{\'i}a} and Casewell, {Nicholas R}",
year = "2023",
month = dec,
day = "14",
doi = "10.1038/s41467-023-43510-w",
language = "English",
volume = "14",
pages = "1--15",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Repurposed drugs and their combinations prevent morbidity-inducing dermonecrosis caused by diverse cytotoxic snake venoms

AU - Hall, Steven R

AU - Rasmussen, Sean A

AU - Crittenden, Edouard

AU - Dawson, Charlotte A

AU - Bartlett, Keirah E

AU - Westhorpe, Adam P

AU - Albulescu, Laura-Oana

AU - Kool, Jeroen

AU - Gutiérrez, José María

AU - Casewell, Nicholas R

PY - 2023/12/14

Y1 - 2023/12/14

N2 - Morbidity from snakebite envenoming affects approximately 400,000 people annually. Tissue damage at the bite-site often leaves victims with catastrophic life-long injuries and is largely untreatable by current antivenoms. Repurposed small molecule drugs that inhibit specific snake venom toxins show considerable promise for tackling this neglected tropical disease. Using human skin cell assays as an initial model for snakebite-induced dermonecrosis, we show that the drugs 2,3-dimercapto-1-propanesulfonic acid (DMPS), marimastat, and varespladib, alone or in combination, inhibit the cytotoxicity of a broad range of medically important snake venoms. Thereafter, using preclinical mouse models of dermonecrosis, we demonstrate that the dual therapeutic combinations of DMPS or marimastat with varespladib significantly inhibit the dermonecrotic activity of geographically distinct and medically important snake venoms, even when the drug combinations are delivered one hour after envenoming. These findings strongly support the future translation of repurposed drug combinations as broad-spectrum therapeutics for preventing morbidity caused by snakebite.

AB - Morbidity from snakebite envenoming affects approximately 400,000 people annually. Tissue damage at the bite-site often leaves victims with catastrophic life-long injuries and is largely untreatable by current antivenoms. Repurposed small molecule drugs that inhibit specific snake venom toxins show considerable promise for tackling this neglected tropical disease. Using human skin cell assays as an initial model for snakebite-induced dermonecrosis, we show that the drugs 2,3-dimercapto-1-propanesulfonic acid (DMPS), marimastat, and varespladib, alone or in combination, inhibit the cytotoxicity of a broad range of medically important snake venoms. Thereafter, using preclinical mouse models of dermonecrosis, we demonstrate that the dual therapeutic combinations of DMPS or marimastat with varespladib significantly inhibit the dermonecrotic activity of geographically distinct and medically important snake venoms, even when the drug combinations are delivered one hour after envenoming. These findings strongly support the future translation of repurposed drug combinations as broad-spectrum therapeutics for preventing morbidity caused by snakebite.

KW - Mice

KW - Humans

KW - Animals

KW - Snake Bites/drug therapy

KW - Snake Venoms/toxicity

KW - Drug Combinations

U2 - 10.1038/s41467-023-43510-w

DO - 10.1038/s41467-023-43510-w

M3 - Journal article

C2 - 38097534

VL - 14

SP - 1

EP - 15

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 7812

ER -