Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Antiviral Effect of Antimicrobial Peptoids and a Murine Model of Respiratory Coronavirus Infection

Maxim Lebedev
ORCID logo ,
Aaron Benjamin
ORCID logo ,
Sathish Kumar
,
Natalia Molchanova
,
Jennifer S. Lin
,
Kent J. Koster
,
Julian L. Leibowitz
,
Annelise E. Barron
ORCID logo ,
Jeffrey D. Cirillo
*
Version 1 : Received: 21 February 2024 / Approved: 21 February 2024 / Online: 22 February 2024 (09:24:34 CET)

A peer-reviewed article of this Preprint also exists.

Lebedev, M.; Benjamin, A.B.; Kumar, S.; Molchanova, N.; Lin, J.S.; Koster, K.J.; Leibowitz, J.L.; Barron, A.E.; Cirillo, J.D. Antiviral Effect of Antimicrobial Peptoid TM9 and Murine Model of Respiratory Coronavirus Infection. Pharmaceutics 2024, 16, 464. Lebedev, M.; Benjamin, A.B.; Kumar, S.; Molchanova, N.; Lin, J.S.; Koster, K.J.; Leibowitz, J.L.; Barron, A.E.; Cirillo, J.D. Antiviral Effect of Antimicrobial Peptoid TM9 and Murine Model of Respiratory Coronavirus Infection. Pharmaceutics 2024, 16, 464.

Abstract

New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study TM9 was effective against three murine coronavirus strains, demonstrating the therapeutic window is large enough to allow use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

Keywords

Peptoid; MHV; SARS-CoV-2; Antimicrobials

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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