Scorpion-Derived Antiviral Peptides with a Special Focus on Medically Important Viruses: An Update

Hidan, Moulay Abdelmonaim El; Laaradia, Mehdi Ait; Hiba, Omar El; Draoui, Ahmed; Aimrane, Abdelmohcine; Kahime, Kholoud

doi:10.1155/2021/9998420

Cited by 9 publications

(8 citation statements)

References 59 publications

(98 reference statements)

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“…Importantly, it was demonstrated that BmKn2-T5 exhibits significant inhibitory activity at the early stages of EV71, especially in attachment and entry. This phenomenon is different from the action stages of most scorpion venom-related antiviral peptides reported in the literature, such as Ctry2459, Hp1090, Hp1036, Hp1239, Kn2-7, and mucroporin-M1, which exert antiviral activity by inactivating infectious viral particles or acting at post-entry stages [23,49]. These data suggest that BmKn2-T5 may affect the early stages of EV71 via a novel antiviral mechanism.…”

Section: Discussioncontrasting

confidence: 59%

Scorpion Venom Antimicrobial Peptide Derivative BmKn2-T5 Inhibits Enterovirus 71 in the Early Stages of the Viral Life Cycle In Vitro

Xia,

Wang,

Chen

et al. 2024

Biomolecules

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Enterovirus 71 (EV71), a typical representative of unenveloped RNA viruses, is the main pathogenic factor responsible for hand, foot, and mouth disease (HFMD) in infants. This disease seriously threatens the health and lives of humans worldwide, especially in the Asia–Pacific region. Numerous animal antimicrobial peptides have been found with protective functions against viruses, bacteria, fungi, parasites, and other pathogens, but there are few studies on the use of scorpion-derived antimicrobial peptides against unenveloped viruses. Here, we investigated the antiviral activities of scorpion venom antimicrobial peptide BmKn2 and five derivatives, finding that BmKn2 and its derivative BmKn2-T5 exhibit a significant inhibitory effect on EV71. Although both peptides exhibit characteristics typical of amphiphilic α-helices in terms of their secondary structure, BmKn2-T5 displayed lower cellular cytotoxicity than BmKn2. BmKn2-T5 was further found to inhibit EV71 in a dose-dependent manner in vitro. Moreover, time-of-drug-addition experiments showed that BmKn2-T5 mainly restricts EV71, but not its virion or replication, at the early stages of the viral cycle. Interestingly, BmKn2-T5 was also found to suppress the replication of the enveloped viruses DENV, ZIKV, and HSV-1 in the early stages of the viral cycle, which suggests they may share a common early infection step with EV71. Together, the results of our study identified that the scorpion-derived antimicrobial peptide BmKn2-T5 showed valuable antiviral properties against EV71 in vitro, but also against other enveloped viruses, making it a potential new candidate therapeutic molecule.

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Section: Discussioncontrasting

confidence: 59%

Scorpion Venom Antimicrobial Peptide Derivative BmKn2-T5 Inhibits Enterovirus 71 in the Early Stages of the Viral Life Cycle In Vitro

Xia,

Wang,

Chen

et al. 2024

Biomolecules

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“…31,32 Moreover, the antiviral activity of several scorpion venom peptides against a wide range of viruses including SARS-coronavirus have been con rmed and several mechanisms have been suggested. [9][10][11][12][13][14][15][16][17] A recent molecular docking study 33 has revealed the ability of some known antiviral scorpion venom peptides to interact with the SARS-CoV-2 spike RBD. However, no supporting experimental biological data were provided.…”

Section: Discussionmentioning

confidence: 99%

“…7,8 Scorpion venoms are known to be rich in these conformationally constrained peptides of which several have been proven to possess antiviral activity against a wide range of viruses. [9][10][11][12][13][14][15][16][17][18] An example is the broad-spectrum antiviral venom peptide, Ev37 from the scorpion Euscorpiops validus that was found to be able to inhibit dengue virus type 2 (DENV-2), hepatitis C (HCV), Zika virus (ZIKV) and herpes simplex type I (HSV-1) in a dose dependent manner at noncytotoxic concentrations. 14 Ev37 exhibits its action via alkalizing acidic organelles to prevent low pH-dependent fusion of the viral membrane-endosomal membrane, which mainly blocks the release of the viral genome from the endosome to the cytoplasm and then restricts viral late entry.…”

Section: Introductionmentioning

confidence: 99%

Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS- CoV-2 activity

Ghazal

Clarke

Abdel-Rahman

et al. 2023

Preprint

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The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly constrained peptides, several of which have demonstrated strong antiviral activity against a range of viruses. We have generated the first annotated reference transcriptome for the Androctonus amoreuxi venom gland and used transcriptome mining, circular dichroism and mass spectrometric analysis to characterize fifteen new venom peptides. Some of these peptides were tested for their ability to bind to the SARS-CoV-2 spike protein and to inhibit the spike RBD - hACE2 interaction that precedes virus entry into the cell using a surface plasmon resonance-based assay. Seven peptides showed dose-dependent inhibitory effects. The most active peptide was synthesized using solid phase peptide synthesis and tested for its antiviral activity against SARS-CoV-2 (Lineage B.1.1.7). On exposure of replication-competent SARS-CoV-2 to the synthetic peptide, we observed a two log10 PFU/mL reduction at sub-micromolar concentrations of the peptide compared to virus exposed to medium alone. Our results show that scorpion venom peptides could inhibit the SARS-CoV-2 spike RBD - hACE2 interaction, exhibit anti-SARS-CoV-2 activity through other unexplored modes of actions and represent excellent scaffolds for design of novel anti-SARS-CoV-2 constrained peptides.

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“…From a comparative genomics perspective, this provides a huge library of molecules to study the effect of structural changes on potency and may be useful in structure–activity relationship (SAR) studies for therapeutic development. AMPs have also been discovered in scorpions; some of those appear to have anti-viral activity [ 28 – 30 ]. Frog AMPs have been classified into 40 peptide families, with some additional “orphan AMPs” that do not fit into the 40 families [ 27 ].…”

Section: Comparative Genomics Applications For Human Healthmentioning

confidence: 99%

The NIH Comparative Genomics Resource: addressing the promises and challenges of comparative genomics on human health

Bornstein,

Gryan,

Chang

et al. 2023

BMC Genomics

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Comparative genomics is the comparison of genetic information within and across organisms to understand the evolution, structure, and function of genes, proteins, and non-coding regions (Sivashankari and Shanmughavel, Bioinformation 1:376-8, 2007). Advances in sequencing technology and assembly algorithms have resulted in the ability to sequence large genomes and provided a wealth of data that are being used in comparative genomic analyses. Comparative analysis can be leveraged to systematically explore and evaluate the biological relationships and evolution between species, aid in understanding the structure and function of genes, and gain a better understanding of disease and potential drug targets. As our knowledge of genetics expands, comparative genomics can help identify emerging model organisms among a broader span of the tree of life, positively impacting human health. This impact includes, but is not limited to, zoonotic disease research, therapeutics development, microbiome research, xenotransplantation, oncology, and toxicology. Despite advancements in comparative genomics, new challenges have arisen around the quantity, quality assurance, annotation, and interoperability of genomic data and metadata. New tools and approaches are required to meet these challenges and fulfill the needs of researchers. This paper focuses on how the National Institutes of Health (NIH) Comparative Genomics Resource (CGR) can address both the opportunities for comparative genomics to further impact human health and confront an increasingly complex set of challenges facing researchers.

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Scorpion-Derived Antiviral Peptides with a Special Focus on Medically Important Viruses: An Update

Cited by 9 publications

References 59 publications

Scorpion Venom Antimicrobial Peptide Derivative BmKn2-T5 Inhibits Enterovirus 71 in the Early Stages of the Viral Life Cycle In Vitro

Scorpion Venom Antimicrobial Peptide Derivative BmKn2-T5 Inhibits Enterovirus 71 in the Early Stages of the Viral Life Cycle In Vitro

Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS- CoV-2 activity

The NIH Comparative Genomics Resource: addressing the promises and challenges of comparative genomics on human health

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