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Antiviral activities and applications of ribosomally synthesized and post-translationally modified peptides (RiPPs) - PubMed

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Antiviral activities and applications of ribosomally synthesized and post-translationally modified peptides (RiPPs)

Yuxin Fu et al. Cell Mol Life Sci. 2021 Apr.

Abstract

The emergence and re-emergence of viral epidemics and the risks of antiviral drug resistance are a serious threat to global public health. New options to supplement or replace currently used drugs for antiviral therapy are urgently needed. The research in the field of ribosomally synthesized and post-translationally modified peptides (RiPPs) has been booming in the last few decades, in particular in view of their strong antimicrobial activities and high stability. The RiPPs with antiviral activity, especially those against enveloped viruses, are now also gaining more interest. RiPPs have a number of advantages over small molecule drugs in terms of specificity and affinity for targets, and over protein-based drugs in terms of cellular penetrability, stability and size. Moreover, the great engineering potential of RiPPs provides an efficient way to optimize them as potent antiviral drugs candidates. These intrinsic advantages underscore the good therapeutic prospects of RiPPs in viral treatment. With the aim to highlight the underrated antiviral potential of RiPPs and explore their development as antiviral drugs, we review the current literature describing the antiviral activities and mechanisms of action of RiPPs, discussing the ongoing efforts to improve their antiviral potential and demonstrate their suitability as antiviral therapeutics. We propose that antiviral RiPPs may overcome the limits of peptide-based antiviral therapy, providing an innovative option for the treatment of viral disease.

Keywords: Antiviral activity; Antiviral mechanism; Engineering; RiPPs.

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Figures

Fig. 1
Fig. 1

Schematic model of known antiviral mechanisms of RiPPs. Antiviral RiPPs exert their activity at different phases of the viral infection process. In the column on the right, several antiviral RiPPs are grouped based on their antiviral phases and mode of action. If known, the specific target is also shown

Fig. 2
Fig. 2

Representative structures of eight selected RiPP families. Post-translational modification(s) on each structure are highlighted in yellow and blue. Abu α-aminobutyric acid, Dha dehydroalanine, Dhb dehydrobutyrine, Orn Ornithine, lab labionin

Fig. 3
Fig. 3

Examples of some of the engineered modifications made to RiPPs to optimize or create novel antiviral activities. a Biotinylated duramycin; b Modifications made to the kalata B1, MCoTI-I and MCoTI-II framework. The locations of the modifications introduced into the cyclotide framework are illustrated using the MCoTI-II structure (pdb ID: 1IB9)

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