Investigating the mechanism(s) of antiviral action of ribosomally synthesized and post-translationally modified peptides with a focus on labyrinthopeptides

Sultanji, Sumayra (2024) Investigating the mechanism(s) of antiviral action of ribosomally synthesized and post-translationally modified peptides with a focus on labyrinthopeptides. Master's Thesis / Essay, Biomolecular Sciences.

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Abstract

Ribosomally synthesized and post-translationally modified Peptides (RiPPs) are known for their structural and functional diversity. These peptides are modified after ribosomal synthesis, leading to the formation of unique stable structures. Lanthipeptides, a subgroup of RiPPs, are well-characterized for their antimicrobial activity and have the incorporation of noncanonical amino acids – Lanthionine and Methyllanthionine. This essay explores the structural dynamics and biosynthetic pathways of Lanthipeptides, with a particular focus on Class III lanthipeptides - the Labyrinthopeptides - LabyA1 and LabyA2. It investigates their structural and biosynthetic aspects, with an emphasis on their antiviral activity. The mode of antiviral action of Labyrinthopeptides involves selective virolytic effects and lipid interaction, where Labyrinthopeptides act as entry inhibitors by targeting the lipid envelope, specifically phosphatidylethanolamine (PE). LabyA1 demonstrates dual anti-HIV and anti-HSV activity, outperforming established drugs in efficacy. Additionally, LabyA1 exhibits promising anti-ZIKV and anti-DENV activity by interfering with virus entry into target cells. To understand mechanistic aspects of the antiviral action, a comparative analysis of labyrinthopeptides with other antiviral lanthipeptides, Duramycin and Cinnamycin, focusing on structural parallels is performed. The presence of specific hydrophobic and hydrophilic ends, along with potential Phosphatidylethanolamine-

Item Type:	Thesis (Master's Thesis / Essay)
Supervisor name:	Moll, G.N. and Jong, A. de
Degree programme:	Biomolecular Sciences
Thesis type:	Master's Thesis / Essay
Language:	English
Date Deposited:	13 Mar 2024 12:13
Last Modified:	13 Mar 2024 12:13
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/32050

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