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

Ahmad Ghazal; David J.  Clarke; Mohamed A. Abdel-Rahman; Antonio Ribeiro; Elaina Collie-Duguid; Craig Pattinson; Kate Burgoyne; Taj Muhammad; Sanad Muayad Alfadhel; Zeynab Heidari; Reham Samir; Mariam Gerges; Istifanus Nkene; Rosa Angela Colamarino; Karolin Hijazi; Wael E Houssen

doi:10.1016/j.peptides.2023.171139

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

Ahmad Ghazal, David J. Clarke, Mohamed A. Abdel-Rahman, Antonio Ribeiro, Elaina Collie-Duguid, Craig Pattinson, Kate Burgoyne, Taj Muhammad, Sanad Muayad Alfadhel, Zeynab Heidari, Reham Samir, Mariam Gerges, Istifanus Nkene, Rosa Angela Colamarino, Karolin Hijazi, Wael E Houssen^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive 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 high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize twelve previously undescribed venom peptides. Selected peptides were tested for binding to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and inhibition of the spike RBD – human angiotensin-converting enzyme 2 (hACE2) interaction using surface plasmon resonance-based assays. Seven peptides showed dose-dependent inhibitory effects, albeit with IC50 in the high micromolar range (117-1202 µM). 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 to the synthetic peptide of a human lung cell line infected with replication-competent SARS-CoV-2, we observed an IC50 of 200 nM, which was nearly 600-fold lower than that observed in the RBD – hACE2 binding inhibition assay. Our results show that scorpion venom peptides can inhibit the SARS-CoV-2 replication although unlikely through inhibition of spike RBD – hACE2 interaction as the primary mode of action. Scorpion venom peptides represent excellent scaffolds for design of novel anti-SARS-CoV-2 constrained peptides. Future studies should fully explore their antiviral mode of action as well as the structural dynamics of inhibition of target virus-host interactions.

Original language	English
Article number	171139
Number of pages	11
Journal	Peptides
Volume	173
Early online date	10 Jan 2024
DOIs	https://doi.org/10.1016/j.peptides.2023.171139
Publication status	Published - Mar 2024

Bibliographical note

Open Access through the Elsevier Agreement
We are very grateful to Prof Moustafa M. Fouda, the CBD National Focal point of Egypt for providing the PIC to conduct this research using the scorpion, A. amoreuxi collected from Egypt. We would like to thank Prof Samy Zalat, Zoology Department, Faculty of Science, Suez Canal University, Egypt, for his valuable advice on the application process to the CBD National Focal point of Egypt. We would like to thank Dr Farhan Ali and Dr Magnus Alphey, University of St Andrews for their help with the CD analysis of our peptides. We would like to acknowledge the support of Digital Research and the Maxwell high performance compute cluster, University of Aberdeen.

Data Availability Statement

The A. amoreuxi transcriptome data is available at GEO. Accession number: GSE221799; Token number cfmxcaialxkxjwv.

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Cite this

Ghazal, A., Clarke, D. J., Abdel-Rahman, M. A., Ribeiro, A., Collie-Duguid, E., Pattinson, C., Burgoyne, K., Muhammad, T., Alfadhel, S. M., Heidari, Z., Samir, R., Gerges, M., Nkene, I., Colamarino, R. A., Hijazi, K., & Houssen, W. E. (2024). Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity. Peptides. Peptides, 173, Article 171139. https://doi.org/10.1016/j.peptides.2023.171139

Ghazal, A, Clarke, DJ, Abdel-Rahman, MA, Ribeiro, A , Collie-Duguid, E, Pattinson, C, Burgoyne, K, Muhammad, T, Alfadhel, SM, Heidari, Z, Samir, R, Gerges, M, Nkene, I, Colamarino, RA , Hijazi, K & Houssen, WE 2024, 'Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity. Peptides', Peptides, vol. 173, 171139. https://doi.org/10.1016/j.peptides.2023.171139

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title = "Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity. Peptides",

abstract = "The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive 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 high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize twelve previously undescribed venom peptides. Selected peptides were tested for binding to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and inhibition of the spike RBD – human angiotensin-converting enzyme 2 (hACE2) interaction using surface plasmon resonance-based assays. Seven peptides showed dose-dependent inhibitory effects, albeit with IC50 in the high micromolar range (117-1202 µM). 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 to the synthetic peptide of a human lung cell line infected with replication-competent SARS-CoV-2, we observed an IC50 of 200 nM, which was nearly 600-fold lower than that observed in the RBD – hACE2 binding inhibition assay. Our results show that scorpion venom peptides can inhibit the SARS-CoV-2 replication although unlikely through inhibition of spike RBD – hACE2 interaction as the primary mode of action. Scorpion venom peptides represent excellent scaffolds for design of novel anti-SARS-CoV-2 constrained peptides. Future studies should fully explore their antiviral mode of action as well as the structural dynamics of inhibition of target virus-host interactions.",

author = "Ahmad Ghazal and Clarke, {David J.} and Abdel-Rahman, {Mohamed A.} and Antonio Ribeiro and Elaina Collie-Duguid and Craig Pattinson and Kate Burgoyne and Taj Muhammad and Alfadhel, {Sanad Muayad} and Zeynab Heidari and Reham Samir and Mariam Gerges and Istifanus Nkene and Colamarino, {Rosa Angela} and Karolin Hijazi and Houssen, {Wael E}",

note = "Open Access through the Elsevier Agreement We are very grateful to Prof Moustafa M. Fouda, the CBD National Focal point of Egypt for providing the PIC to conduct this research using the scorpion, A. amoreuxi collected from Egypt. We would like to thank Prof Samy Zalat, Zoology Department, Faculty of Science, Suez Canal University, Egypt, for his valuable advice on the application process to the CBD National Focal point of Egypt. We would like to thank Dr Farhan Ali and Dr Magnus Alphey, University of St Andrews for their help with the CD analysis of our peptides. We would like to acknowledge the support of Digital Research and the Maxwell high performance compute cluster, University of Aberdeen.",

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doi = "10.1016/j.peptides.2023.171139",

language = "English",

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T1 - Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity. Peptides

AU - Ghazal, Ahmad

AU - Clarke, David J.

AU - Abdel-Rahman, Mohamed A.

AU - Ribeiro, Antonio

AU - Collie-Duguid, Elaina

AU - Pattinson, Craig

AU - Burgoyne, Kate

AU - Muhammad, Taj

AU - Alfadhel, Sanad Muayad

AU - Heidari, Zeynab

AU - Samir, Reham

AU - Gerges, Mariam

AU - Nkene, Istifanus

AU - Colamarino, Rosa Angela

AU - Hijazi, Karolin

AU - Houssen, Wael E

N1 - Open Access through the Elsevier Agreement We are very grateful to Prof Moustafa M. Fouda, the CBD National Focal point of Egypt for providing the PIC to conduct this research using the scorpion, A. amoreuxi collected from Egypt. We would like to thank Prof Samy Zalat, Zoology Department, Faculty of Science, Suez Canal University, Egypt, for his valuable advice on the application process to the CBD National Focal point of Egypt. We would like to thank Dr Farhan Ali and Dr Magnus Alphey, University of St Andrews for their help with the CD analysis of our peptides. We would like to acknowledge the support of Digital Research and the Maxwell high performance compute cluster, University of Aberdeen.

PY - 2024/3

Y1 - 2024/3

N2 - The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive 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 high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize twelve previously undescribed venom peptides. Selected peptides were tested for binding to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and inhibition of the spike RBD – human angiotensin-converting enzyme 2 (hACE2) interaction using surface plasmon resonance-based assays. Seven peptides showed dose-dependent inhibitory effects, albeit with IC50 in the high micromolar range (117-1202 µM). 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 to the synthetic peptide of a human lung cell line infected with replication-competent SARS-CoV-2, we observed an IC50 of 200 nM, which was nearly 600-fold lower than that observed in the RBD – hACE2 binding inhibition assay. Our results show that scorpion venom peptides can inhibit the SARS-CoV-2 replication although unlikely through inhibition of spike RBD – hACE2 interaction as the primary mode of action. Scorpion venom peptides represent excellent scaffolds for design of novel anti-SARS-CoV-2 constrained peptides. Future studies should fully explore their antiviral mode of action as well as the structural dynamics of inhibition of target virus-host interactions.

AB - The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive 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 high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize twelve previously undescribed venom peptides. Selected peptides were tested for binding to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and inhibition of the spike RBD – human angiotensin-converting enzyme 2 (hACE2) interaction using surface plasmon resonance-based assays. Seven peptides showed dose-dependent inhibitory effects, albeit with IC50 in the high micromolar range (117-1202 µM). 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 to the synthetic peptide of a human lung cell line infected with replication-competent SARS-CoV-2, we observed an IC50 of 200 nM, which was nearly 600-fold lower than that observed in the RBD – hACE2 binding inhibition assay. Our results show that scorpion venom peptides can inhibit the SARS-CoV-2 replication although unlikely through inhibition of spike RBD – hACE2 interaction as the primary mode of action. Scorpion venom peptides represent excellent scaffolds for design of novel anti-SARS-CoV-2 constrained peptides. Future studies should fully explore their antiviral mode of action as well as the structural dynamics of inhibition of target virus-host interactions.

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

Abstract

Bibliographical note

Data Availability Statement

Access to Document

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Cite this