Antiviral and antibacterial peptides: Mechanisms of action

Abstract

Antimicrobial peptides (AMPs) present promising alternatives for addressing bacterial and viral multidrug resistance due to their distinctive properties. Understanding the mechanisms of these compounds is essential for achieving this objective. Therefore, this comprehensive review aims to highlight primary natural sources of AMPs and elucidate various aspects of the modes of action of antiviral and antibacterial peptides (ABPs). It emphasizes that antiviral peptides (AVPs) can disrupt the replication cycle of both enveloped and non-enveloped viruses at several stages, including pre-fusion, fusion, and post-entry into the host cell. Additionally, the review discusses the inhibitory effects of ABPs on bacterial growth, outlining their extracellular actions as well as their intracellular activities following membrane translocation. Factors such as structure, size, electric charge, environmental factors, degrading enzymes, and microbial resistance against AMPs can affect the function of AMPs.

Keywords: Antibacterial peptide; Antimicrobial peptide; Antiviral peptide; Drug resistance; Mechanism of action.

Fig. 1

Statics of the antimicrobial peptides. (A) Source of antimicrobial peptides (in total: 3569) and (B) animal derived antimicrobial peptide percentages (in total: 2600) in the antimicrobial peptide database https://aps.unmc.edu/in December 2023.

Fig. 2

Potential mechanisms of antiviral peptides (AVPs) against enveloped viruses. Part A includes pre-fusion antiviral activities of cationic peptides that prevent viral-cellular interaction, and B represents fusion and intracellular antiviral activity of AVPs.

Fig. 3

The schematic scheme of antibacterial action of AMPs. Extracellular antibacterial activity of AMPs is shown in right, which represents non-membrane (1) and membrane (2) action model. Left side shows Intracellular antibacterial activity of AMPs after translocation through the membrane. Based on interaction site they can inhibit bacterial energy metabolism system (3), cell division, replication, and transcription (4), translation and protein folding (5). OM: outer membrane; PG; peptidoglycan; IM; inner membrane; ETC: electron transport chain; EIT: energy independent translocation; EDT: energy dependent translocation.

Fig. 4

Possible anti-biofilm effect of AMPs in different stages of biofilm development process. As shown in the above, biofilm formation consists of three main stages. Peptides may interface with enhancer and inhibitor factors to block this process or degrade biofilm three-dimensional structure. Furthermore, in some conditions, such as electrostatic interactions, the promoting effect is not unexpected.