Despite the availability of vaccines, COVID-19 continues to be aggressive, especially in immunocompromised individuals. Therefore, the development of a specific therapeutic agent with antiviral activity against SARS-CoV-2 is necessary. The infection pathway starts when the receptor binding domain of the viral spike protein interacts with the angiotensin converting enzyme 2 (ACE2), which acts as a host receptor for the RBD expressed on the host cell surface. In this scenario, ACE2 analogs binding to the RBD and preventing the cell entry can be promising antiviral agents. Most of the ACE2 residues involved in the interaction belong to the α1 helix, more specifically to the minimal fragment ACE2(24–42). In order to increase the stability of the secondary structure and thus antiviral activity, we designed different triazole-stapled analogs, changing the position and the number of bridges. The peptide called P3, which has the triazole-containing bridge in the positions 36–40, showed promising antiviral activity at micromolar concentrations assessed by plaque reduction assay. On the other hand, the double-stapled peptide P4 lost the activity, showing that excessive rigidity disfavors the interaction with the RBD.

High-Temperature Fast-Stirring Solid-Phase synthesis accelerated the preparation of peptides containing multipleN-glycosylation sites.

: Eradication of malaria remains one of the main aims of medicine. Despite progress in malaria treatment, mortality rate remains high, especially in the poorest parts of the world. Therefore, preve...

Thymosins are small proteins found mainly in the thymus. They are involved in several biological processes, including immunoregulation, angiogenesis, and anti-inflammatory activity. Due to these multiple activities, thymosins are widely used as therapeutics. In fact, these peptides have shown interesting results in the treatment of eye disorders, anticancer therapy, and dysregulated immune disorders. We analyzed the thymosins therapeutic patent landscape describing the most significant patents published after 2018 and originally written in English, classified according to the different type of functions and diseases. We searched 'Thymosin' on Patentscope and Espacenet. Thymalfasin (Zadaxin) is the only FDA-approved thymosine-based drug used to treat chronic hepatitis B and C and as a chemotherapy inducer. This outcome demonstrates how thymosins can be exploited as therapeutics, especially in immunological and anti-cancer therapies. However, the development of modified thymosins could expand their therapeutic interest and application in different diseases. In fact, by chemical modifications, it is possible to increase proteolytic stability in the biological environment, enhance cell permeability, and stabilize the secondary structure of the peptide. Finally, the development of shorter sequences could reduce the cost and production time of these thymosin-based drugs.

The increase in antibacterial resistance is one of the greatest challenges in modern medicine, driving an urgent need to develop new drugs to combat resistant pathogens. Peptides represent a promising class of molecules that can be efficiently designed to exhibit high antimicrobial efficacy. Recently, we have highlighted how prestructuring by a triazolyl-bridge significantly enhances the activity of an antimicrobial peptide. To learn more from these findings, the aim of this study is to relate the NMR-based structure of a triazolyl-bridged peptide to its antimicrobial activity against Gram-positive and Gram-negative bacteria in comparison to its linear analogues. As we show, the triazole modification indeed induces a well-defined α-helical structure, resulting in an improved positive electrostatic surface potential on one side of the peptide and clustering of hydrophilic and hydrophobic residues on opposite surface areas of the molecule. Systematic alanine substitution further suggested that the side chains of arginine 3 and 7 and of asparagine 11 have a stronger productive impact on antimicrobial activity than those of lysine 4, 8, and 12. As shown by micelle-bound peptide structures determined by NMR, we identify arginine 3 and asparagine 11 as presumable membrane-interacting residues. Collectively, our NMR-based analysis provides evidence that an α-helical structure enhances antimicrobial activity by creating positively charged and hydrophilic, and hydrophobic areas as molecular surface signatures, potentially promoting the interaction of the peptide with the cellular target membrane.

To date, the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) COVID‐19 pandemic continues to be a potentially lethal disease. Although both vaccines and specific antiviral drugs have been approved, the search for more specific therapeutic approaches is still ongoing. The infection mechanism of SARS‐CoV‐2 consists of several stages, and each one can be selectively blocked to disrupt viral infection. Peptides are a promising class of antiviral compounds, which may be suitably modified to be more stable, more effective, and more selective towards a specific viral replication step. The latter two goals might be obtained by increasing the specificity and/or the affinity of the interaction with a specific target and often imply the stabilization of the secondary structure of the active peptide. This review is focused on modified antiviral peptides against SARS‐CoV‐2 acting at different stages of virus replication, including ACE2‐RBD interaction, membrane fusion mechanism, and the proteolytic cleavage by different viral proteases. Therefore, the landscape presented herein provides a useful springboard for the design of new and powerful antiviral therapeutics.