TY - JOUR
AU - Ghazal, Ahmad
AU - Clarke, David J.
AU - Abdelrahman, Mohamed
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
PY - 2023
DA - December
TI - Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity. Peptides
JO - Peptides
VL - 173
DO - https://doi.org/10.1016/j.peptides.2023.171139
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 theAndroctonus amoreuxivenom 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 IC50in 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 IC50of 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.of Aberdeen.
PB - Elsevier
UR - https://hdl.handle.net/2164/22526
KW - Coronavirus (COVID-19)
ER