A Review: The Antiviral Activity of Cyclic Peptides

Abstract

In the design and development of therapeutic agents, macromolecules with restricted structures have stronger competitive edges than linear biological entities since cyclization can overcome the limitations of linear structures. The common issues of linear peptides include susceptibility to degradation of the peptidase enzyme, off-target effects, and necessity of routine dosing, leading to instability and ineffectiveness. The unique conformational constraint of cyclic peptides provides a larger surface area to interact with the target at the same time, improving the membrane permeability and in vivo stability compared to their linear counterparts. Currently, cyclic peptides have been reported to possess various activities, such as antifungal, antiviral and antimicrobial activities. To date, there is emerging interest in cyclic peptide therapeutics, and increasing numbers of clinically approved cyclic peptide drugs are available on the market. In this review, the medical significance of cyclic peptides in the defence against viral infections will be highlighted. Except for chikungunya virus, which lacks specific antiviral treatment, all the viral diseases targeted in this review are those with effective treatments yet with certain limitations to date. Thus, strategies and approaches to optimise the antiviral effect of cyclic peptides will be discussed along with their respective outcomes. Apart from isolated naturally occurring cyclic peptides, chemically synthesized or modified cyclic peptides with antiviral activities targeting coronavirus, herpes simplex viruses, human immunodeficiency virus, Ebola virus, influenza virus, dengue virus, five main hepatitis viruses, termed as type A, B, C, D and E and chikungunya virus will be reviewed herein. Graphical Abstract

Mixture-Based Screening of Focused Combinatorial Libraries by NMR: Application to the Antiapoptotic Protein hMcl-1

“…In our application, a validated (by means of NMR spectroscopy and ITC), low micromolar agent with reasonably low molecular weight and ample possibilities for optimizations was identified, representing in principle a novel chemotype targeting hMcl-1. The approach is relatively simple and could find general applicability in a variety of scenarios, including, for example, the creation of libraries of cyclic peptides, ,− or similar to the f HTS by NMR, for the optimization of an initial binding scaffold identified by other methods.…”

Influence of heterochirality on the structure, dynamics, biological properties of cyclic(PFPF) tetrapeptides obtained by solvent-free ball mill mechanosynthesis

“…Their cyclic nature provides them with increased stability, target specificity, and often enhanced bioactivity compared to linear peptides [9][10][11][12] . Cyclic peptides are known to exhibit a wide spectrum of biological activities, such as antibacterial, antiviral, antifungal, anticancer and immunosuppressive 1,6,[13][14][15][16][17][18][19][20][21][22][23][24] . Moreover, these compounds are characterized by additional resistance to enzymatic degradation by exoproteases that preferentially cleave near the N-or C-termini of peptides 25 .…”

Influence of heterochirality on the structure, dynamics, biological properties of cyclic(PFPF) tetrapeptides obtained by solvent-free ball mill mechanosynthesis

“…[9][10][11][12] Cyclic peptides are known to exhibit a wide spectrum of biological activities, such as antibacterial, antiviral, antifungal, anticancer and immunosuppressive. 1,6,[13][14][15][16][17][18][19][20][21][22][23][24] Moreover, these compounds are characterized by additional resistance to enzymatic degradation by exoproteases that preferentially cleave near the N-or C-termini of peptides. 25 In the light of given supra information there is no surprise that over 60% of peptide drugs approved by FDA and EMA exist in the cyclic form.…”