Maxwell Biosciences, a preclinical stage biotechnology company developing CLAROMER brand anti-infectives, announced that the peer-reviewed, open-access journal Pharmaceuticals (MDPI) has published new scientific research findings co-authored by Scientific Advisory Board Member Gill Diamond, University of Louisville, Department of Oral Microbiology and Infectious Diseases and eleven other collaborating academic researchers. Titled Potent Antiviral Activity against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids, the research findings demonstrate that several peptoids exhibit potent in vitro antiviral activity against both HSV-1 and SARS-CoV-2.
As outlined in the paper’s 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 drugs that treat viral infections effectively, and no vaccine to prevent HSV-1 infections exists.
“There’s a huge need for new antiviral agents and whereas new vaccines are now available for SARS-CoV-2, treatments can help those who become infected and develop Covid-19 illness. This paper constitutes the first report of biomimetic antiviral peptoids—stable mimics of natural antiviral peptides—that effectively inactivate two different enveloped viruses, utilizing a mechanism of action similar to that of natural innate immunity. Recurrent HSV-1 infections affect around 177M adult Americans; and of course, SARS-CoV-2 affects us all,” said Dr Diamond.
As detailed in the body of the paper and visualised by cryo-EM images the researchers showed experimentally that antiviral peptoids disrupt the phospholipid envelopes of the viruses by a mechanism similar to that observed for natural human antiviral peptides.
Dr Diamond stated, “The entire research team involved in this study deserves tremendous praise, as interdisciplinary research of this nature is critical to the development of new therapies that are effective against viral infections, while also being safe for human use.” Dr Diamond is continuing to study these promising peptoids now as topical treatments in a rodent model of Herpes Labialis.
Key observations and findings
The antiviral peptoids were synthesised at the DOE-sponsored Molecular Foundry. Their antiviral activity was studied and tested at the University of Louisville with financial support from Maxwell Biosciences. They were designed to function as mimics of natural biological antiviral peptides. Antiviral peptoids have the distinct advantage of being insensitive to the proteases that quickly degrade biological peptides, and thus offer increased bioavailability and stability in the body.
Herpes simplex virus type-1 (HSV-1) infections cause recurrent oral lesions and affect millions in the developed world. HSV-1 is also a major cause of infectious blindness and genital infections worldwide. HSV-1 infections are life-threatening in immunocompromised individuals. Furthermore, there is recent evidence that HSV-1 infections are associated with the pathogenesis of Alzheimer’s disease, magnifying the importance of treating these infections early. HSV-1 virus is transmitted readily through oral secretions. It is estimated that up to 80 per cent of the population is infected with this virus, depending on age and socioeconomic status.
The innate immune system is one of the primary mechanisms for recognising and eliminating viruses and other pathogens from mucosal surfaces.
Challenges of using natural antimicrobial peptides as therapeutics spurred the development of non-natural peptidomimetics such as ‘peptoids’, which are a class of biostable, sequence-specific N-substituted glycine oligomers.
Based on the prior results demonstrating the inactivation of enveloped viruses by antiviral peptides via membrane-disruption mechanisms, Drs Diamond and Barron hypothesised that antimicrobial peptoids designed to mimic natural antiviral peptides could inactivate an enveloped virus such as HSV-1. And since the recently emerged virus SARS-CoV-2 (the etiological agent of COVID-19) is similarly enveloped, they further believed that these peptoids might exhibit activity against this devastating virus.
A library of ten different biomimetic peptoids was tested, by comparison to the natural human host defense peptide LL-37...
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