Identification of brevinin-1EMa-derived stapled peptides as broad-spectrum virus entry blockers

Kim, Mi Il; Pham, Thanh K.; Kim, Da Hee; Park, Minkyung; Kim, Bi-o; Cho, You‐Hee; Kim, Young Woo; Lee, Choong-Ho

doi:10.1016/j.virol.2021.05.004

Cited by 7 publications

(11 citation statements)

References 54 publications

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“…This strategy has recently been widely used against SARS-CoV-2 [49,50], but again it is strictly dependent on the specific virus (or at least virus family) and antigenic variability. On the other hand, several studies have also shown that some antiviral peptides derived from classical AMPs are active against a wide range of enveloped and nonenveloped viruses [51][52][53][54][55][56][57][58].…”

Section: Discussionmentioning

confidence: 99%

Broad-Spectrum Antiviral Activity of the Amphibian Antimicrobial Peptide Temporin L and Its Analogs

Zannella

Chianese

Palomba

et al. 2022

IJMS

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The COVID-19 pandemic has evidenced the urgent need for the discovery of broad-spectrum antiviral therapies that could be deployed in the case of future emergence of novel viral threats, as well as to back up current therapeutic options in the case of drug resistance development. Most current antivirals are directed to inhibit specific viruses since these therapeutic molecules are designed to act on a specific viral target with the objective of interfering with a precise step in the replication cycle. Therefore, antimicrobial peptides (AMPs) have been identified as promising antiviral agents that could help to overcome this limitation and provide compounds able to act on more than a single viral family. We evaluated the antiviral activity of an amphibian peptide known for its strong antimicrobial activity against both Gram-positive and Gram-negative bacteria, namely Temporin L (TL). Previous studies have revealed that TL is endowed with widespread antimicrobial activity and possesses marked haemolytic activity. Therefore, we analyzed TL and a previously identified TL derivative (Pro3, DLeu9 TL, where glutamine at position 3 is replaced with proline, and the D-Leucine enantiomer is present at position 9) as well as its analogs, for their activity against a wide panel of viruses comprising enveloped, naked, DNA and RNA viruses. We report significant inhibition activity against herpesviruses, paramyxoviruses, influenza virus and coronaviruses, including SARS-CoV-2. Moreover, we further modified our best candidate by lipidation and demonstrated a highly reduced cytotoxicity with improved antiviral effect. Our results show a potent and selective antiviral activity of TL peptides, indicating that the novel lipidated temporin-based antiviral agents could prove to be useful additions to current drugs in combatting rising drug resistance and epidemic/pandemic emergencies.

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Section: Discussionmentioning

confidence: 99%

Broad-Spectrum Antiviral Activity of the Amphibian Antimicrobial Peptide Temporin L and Its Analogs

Zannella

Chianese

Palomba

et al. 2022

IJMS

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“…To promote the transition from lab research to practical applications, the overall performance of the bioinspired antibacterial surfaces should be improved enough to cope with complex, transient scenarios in the real world [ 76 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 ]. First, a bioinspired antibacterial surface should be highly adaptive to a wide spectrum of bacteria.…”

Section: Discussionmentioning

confidence: 99%

Recent Progress on Bioinspired Antibacterial Surfaces for Biomedical Application

et al. 2022

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Surface bacterial fouling has become an urgent global challenge that calls for resilient solutions. Despite the effectiveness in combating bacterial invasion, antibiotics are susceptible to causing microbial antibiotic resistance that threatens human health and compromises the medication efficacy. In nature, many organisms have evolved a myriad of surfaces with specific physicochemical properties to combat bacteria in diverse environments, providing important inspirations for implementing bioinspired approaches. This review highlights representative natural antibacterial surfaces and discusses their corresponding mechanisms, including repelling adherent bacteria through tailoring surface wettability and mechanically killing bacteria via engineering surface textures. Following this, we present the recent progress in bioinspired active and passive antibacterial strategies. Finally, the biomedical applications and the prospects of these antibacterial surfaces are discussed.

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“…Moreover, the suggested mechanism of viral particle aggregation indicated that these stapled peptides may be more active toward enveloped viruses. 59 However, the selectivity of stapled antiviral peptides must be thoroughly examined because the viral membrane is mainly derived from host cells. Thus, a further investigation of SARs is required to develop stapled peptides as a new potential class of antiviral agents.…”

Section: Hydrocarbon Stapledmentioning

confidence: 99%

“…Recently, α-helical MAPs have received considerable attention as new alternative antiviral treatments despite their limitations, such as the high production cost of a long sequence, the lack of a helical structure, and their susceptibility to proteolytic degradation. ,− The effects of the all-hydrocarbon stapling system on the antiviral properties of helical peptides have been investigated. ,− Among these investigations, a study was conducted that explored the possibility of developing novel short and stapled membrane-targeting antiviral peptides based on a truncated analog (compound 45 , Table ) of the natural AMP Brevinin-1EMa . The data showed that the stapling system promotes stability against trypsin digestion and improves the antiviral activity of some staple analogs.…”

Section: Application Of An All-hydrocarbon Stapling Approach For the ...mentioning

confidence: 99%

Application of the All-Hydrocarbon Stapling Technique in the Design of Membrane-Active Peptides

2022

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The threats of drug resistance and new emerging pathogens have led to an urgent need to develop alternative treatment therapies. Recently, considerable research efforts have focused on membrane-active peptides (MAPs), a category of peptides in drug discovery with antimicrobial, anticancer, and cell penetration activities that have demonstrated their potential to be multifunctional agents. Nonetheless, natural MAPs have encountered various disadvantages, which mainly include poor bioavailability, the lack of a secondary structure in short peptides, and high production costs for long peptide sequences. Hence, an "all-hydrocarbon stapling system" has been applied to these peptides and proven to effectively stabilize the helical conformations, improving proteolytic resistance and increasing both the potency and the cell permeability. In this review, we summarized and categorized the advances made using this powerful technique in the development of stapled MAPs. Furthermore, outstanding issues and suggestions for future design within each subcategory were thoroughly discussed.

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Identification of brevinin-1EMa-derived stapled peptides as broad-spectrum virus entry blockers

Cited by 7 publications

References 54 publications

Broad-Spectrum Antiviral Activity of the Amphibian Antimicrobial Peptide Temporin L and Its Analogs

Broad-Spectrum Antiviral Activity of the Amphibian Antimicrobial Peptide Temporin L and Its Analogs

Recent Progress on Bioinspired Antibacterial Surfaces for Biomedical Application

Application of the All-Hydrocarbon Stapling Technique in the Design of Membrane-Active Peptides

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