Peptides and Dendrimers: How to Combat Viral and Bacterial Infections

Abstract

The alarming growth of antimicrobial resistance and recent viral pandemic events have enhanced the need for novel approaches through innovative agents that are mainly able to attach to the external layers of bacteria and viruses, causing permanent damage. Antimicrobial molecules are potent broad-spectrum agents with a high potential as novel therapeutics. In this context, antimicrobial peptides, cell penetrating peptides, and antiviral peptides play a major role, and have been suggested as promising solutions. Furthermore, dendrimers are to be considered as suitable macromolecules for the development of advanced nanosystems that are able to complement the typical properties of dendrimers with those of peptides. This review focuses on the description of nanoplatforms constructed with peptides and dendrimers, and their applications.

Keywords: antimicrobial; dendrimer; peptide.

Figure 1

Factors involved in the diffusion of antibiotic resistance: human medicine in the community and in the hospital, animal production, and agriculture and environment.

Figure 2

Dendrimers can be functionalized with antimicrobial peptides (AMPs), cell penetrating peptides (CPPs), and antiviral peptides for applications in fighting bacteria, viruses, and biofilms. Created with BioRender.com.

Figure 3

The main classes of peptides showing antibacterial and antiviral activity. (A) The mechanisms of antibacterial activity proposed for AMPs (barrel-stave, toroidal-pore, and carpet). (B) The hypothesized antiviral mechanisms for AMPs, which involve inhibition of viruses integrating in either the viral envelope or the host cell membrane. (C) The antibacterial mechanism proposed for CPPs, which involves local disruption of bacterial membrane bilayers. (D) The antiviral mechanism of CPPs, involving the formation of inactive aggregates between the fusogenic stretches present in the viral protein and the host cell. (E) The mechanism of antiviral peptides, involving inhibition of viral attachment and penetration. Created with BioRender.com.

Figure 4

Synthetic strategies that can be exploited in dendrimer development. Created with BioRender.com.

Figure 5

(A) Cationic dendrimers and maltose-conjugated dendrimers, the antimicrobial activity of which is related to the electrostatic interaction and consequent permeabilization of the bacterial membranes, or the interaction with specific receptors on the host-cell membrane. (B) Antiviral anionic dendrimers acting on different steps of viral infection. Created with BioRender.com.

Figure 6

Representation of the SPL7013 dendrimer (VivaGel^®) mechanism. (A) The host cell infected by the virus. (B) The host is protected from the infection by treatment with VivaGel^®, which prevents the interaction and fusion of the virus with the host-cell membrane. Created with BioRender.com.