@article{e65e9d7d9e814eaaad9f3a06d70f699b,
title = "Potent antiviral activity against HSV-1 and SARS-CoV-2 by antimicrobial peptoids",
abstract = "Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of antiviral drugs involves the identification of a unique viral target, followed by the design of an agent that addresses that target. Antimicrobial peptides (AMPs) represent a novel source of potential antiviral drugs. AMPs have been shown to inactivate numerous different enveloped viruses through the disruption of their viral envelopes. However, the clinical development of AMPs as antimicrobial therapeutics has been hampered by a number of factors, especially their enzymatically labile structure as peptides. We have examined the antiviral potential of peptoid mimics of AMPs (sequence-specific N-substituted glycine oligomers). These peptoids have the distinct advantage of being insensitive to proteases, and also exhibit increased bioavailability and stability. Our results demonstrate that several peptoids exhibit potent in vitro antiviral activity against both HSV-1 and SARS-CoV-2 when incubated prior to infection. In other words, they have a direct effect on the viral structure, which appears to render the viral particles non-infective. Visualization by cryo-EM shows viral envelope disruption similar to what has been observed with AMP activity against other viruses. Furthermore, we observed no cytotoxicity against primary cultures of oral epithelial cells. These results suggest a common or biomimetic mechanism, possibly due to the differences between the phospholipid head group makeup of viral envelopes and host cell membranes, thus underscoring the potential of this class of molecules as safe and effective broad-spectrum antiviral agents. We discuss how and why differing molecular features between 10 peptoid candidates may affect both antiviral activity and selectivity.",
keywords = "Air-liquid interface, Antivirals, COVID-19, Cytotoxicity, HSV-1, LL-37, Membrane disruption, Peptoids, SARS-CoV-2",
author = "Gill Diamond and Natalia Molchanova and Claudine Herlan and Fortkort, {John A.} and Lin, {Jennifer S.} and Erika Figgins and Nathen Bopp and Ryan, {Lisa K.} and Donghoon Chung and Adcock, {Robert Scott} and Michael Sherman and Barron, {Annelise E.}",
note = "Funding Information: Funding: This work was funded by a grant from Maxwell Biosciences, Inc. to G.D. at University of Louisville, and the U.S. Public Health Services (including an NIH Pioneer Award to Annelise Barron, grant # 1DP1 OD029517-01). Work at the Molecular Foundry was supported by the Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. Funding Information: This work was funded by a grant from Maxwell Biosciences, Inc. to G.D. at University of Louisville, and the U.S. Public Health Services (including an NIH Pioneer Award to Annelise Barron, grant # 1DP1 OD029517-01). Work at the Molecular Foundry was supported by the Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. The authors thank Jillian Cramer for her invaluable assistance with the TEM. This work was performed in part at the Electron Microscopy Center which belongs to the National Science Foundation NNCI Kentucky Multiscale Manufacturing and Nano Integration Node, supported by ECCS-1542174. We also thank H?vard Jenssen (Roskilde University) Michael Connolly, and Stefan Br?se (Karlsruhe Institute of Technology) for their support and mentorship, and Josefine Eilsoe Nielsen and Reidar Lund for helpful comments. Funding Information: Acknowledgments: The authors thank Jillian Cramer for her invaluable assistance with the TEM. This work was performed in part at the Electron Microscopy Center which belongs to the National Science Foundation NNCI Kentucky Multiscale Manufacturing and Nano Integration Node, supported by ECCS-1542174. We also thank H{\aa}vard Jenssen (Roskilde University) Michael Connolly, and Stefan Br{\"a}se (Karlsruhe Institute of Technology) for their support and mentorship, and Josefine Eilsoe Nielsen and Reidar Lund for helpful comments. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2021",
month = apr,
doi = "10.3390/ph14040304",
language = "English (US)",
volume = "14",
journal = "Pharmaceuticals",
issn = "1424-8247",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "4",
}