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 |
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Article number | 171139 |
Number of pages | 11 |
Journal | Peptides |
Volume | 173 |
Early online date | 10 Jan 2024 |
DOIs | |
Publication status | Published - Mar 2024 |
Bibliographical note
Open Access through the Elsevier AgreementWe 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.