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.
The skin secretion of amphibians is known for its high content of bioactive compounds. These bioactive compounds are essential for the advancement of biomedical industries. Four wild green paddy frogs, Hylarana erythraea, were collected from various habitat types within the Langkawi Archipelago. These frogs' skin secretions were collected, extracted, and analysed for their protein compounds together with biomedical potentials using liquid chromatography-mass spectrometry (LC-MS). The total protein concentration of H. erythraea skin secretions was determined as 0.269 mg/mL. Based on the UniProt (Anura) database, we identified 29 proteins. These proteins were categorised as antimicrobial (AMP) (38%), followed by hormone (17%), enzyme (17%), unreviewed proteins (17%), structural proteins (7%), and regulatory proteins (4%). The AMPs identified were from the family of esculentin-1, esculentin-2, brevinin-1, and frenatin-4, while the hormones belonged to the cholecystokinin group. The enzymes detected were adenylate cyclase 9, the suppressor of tumorigenicity 14 protein homolog, and the HGF activator. The structural proteins belonged to toe pad keratin 2 and Krt5.7 proteins, while the single regulatory protein is CCR4-NOT transcription complex subunit 6-like. These proteins have a wide range of biomedical importance, such as wound healings, facilitate digestions, anti-tumours, and anti-cancer effect.
Peptides are promising antagonists against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). To expedite drug discovery, a computational approach is widely employed for the initial screening of anti-SARS-CoV-2 candidates. This study aimed to investigate the potential of peptides from quinoa seed proteins as multi-target antagonists against SARS-CoV-2 spike glycoprotein receptor-binding domain, main protease, and papain-like protease. Five quinoa proteins were hydrolyzed in silico by papain and subtilisin. Among the 1465 peptides generated, seven could interact stably with the key binding residues and catalytic residues of the viral targets, mainly via hydrogen bonds and hydrophobic interactions. The seven peptides were comparable or superior to previously reported anti-SARS-CoV-2 peptides based on docking scores. Key residues in the seven peptides contributing to binding to viral targets were determined by computational alanine scanning. The seven peptides were predicted in silico to be non-toxic and non-allergenic. The peptides ranged between 546.66 and 3974.87 g/mol in molecular mass, besides exhibiting basic and cationic properties (isoelectric points: 8.26-12.10; net charges: 0.1-4.0). Among the seven peptides, VEDKGMMHQQRMMEKAMNIPRMCGTMQRKCRMS was found to bind the largest number of key residues on the targets. In conclusion, seven putative non-toxic, non-allergenic, multi-target anti-SARS-CoV-2 peptides were identified from quinoa seed proteins. The in vitro and in vivo efficacies of the seven peptides against SARS-CoV-2 deserve attention in future bench-top testing.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10989-021-10214-y.