Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Potent Antiviral Activity Against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids

Version 1 : Received: 8 March 2021 / Approved: 9 March 2021 / Online: 9 March 2021 (10:25:03 CET)

A peer-reviewed article of this Preprint also exists.

Diamond, G.; Molchanova, N.; Herlan, C.; Fortkort, J.A.; Lin, J.S.; Figgins, E.; Bopp, N.; Ryan, L.K.; Chung, D.; Adcock, R.S.; Sherman, M.; Barron, A.E. Potent Antiviral Activity against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids. Pharmaceuticals 2021, 14, 304. Diamond, G.; Molchanova, N.; Herlan, C.; Fortkort, J.A.; Lin, J.S.; Figgins, E.; Bopp, N.; Ryan, L.K.; Chung, D.; Adcock, R.S.; Sherman, M.; Barron, A.E. Potent Antiviral Activity against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids. Pharmaceuticals 2021, 14, 304.

Journal reference: Pharmaceuticals 2021, 14, 304
DOI: 10.3390/ph14040304

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 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. Visualization by cryo-EM shows viral envelope disruption similar to what has been observed with AMP activity against other viruses. This suggests a common or biomimetic mechanism, possibly due to the differences between the phospholipid head group makeup of viral envelopes and host cell membranes. Furthermore, we observed no cytotoxicity against primary cultures of oral epithelial cells, thus underscoring the potential of this class of molecules as safe and effective broad-spectrum antiviral agents.

Subject Areas

Antivirals; peptoids; LL-37; air-liquid interface; cytotoxicity; membrane disruption; COVID-19; HSV-1; SARS-CoV-2

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