Project description: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.
Project description:Heloderma horridum horridum commonly known as the scorpion lizard, Mexican scorpion, and beaded lizard, is a venomous reptile native of America. The venom derived from this lizard has potential applications, particularly in treatment of type II diabetes through the peptide Exendin. In this work, H. h. horridum venom was extracted from adult specimens and lyophilized. To characterize the venom, enzymatic assays, including hyaluronidase, phospholipase A2, and proteolytic activity were conducted. A proteomic analysis of the venom was also performed employing bottom-up/shotgun approaches from SDS-PAGE and High pH Reversed-Phase chromatography., besides fractionation of tryptic peptides using a nano-LC-MS/MS. These approaches involved massive sequencing to enhancing the likelihood of detecting an extensive range of venom proteins. The proteins and peptides found in H. h. horridum venom are reviewed according to the classification of the transcriptome previously reported.
Project description:The spider venom-derived peptide GsMTx4 specifically inhibits mechanosensory ion channels. It has been reported that GsMTx4 plays an immunoregulatory role in several inflammatory conditions. Therefore, we administrated GsMTx4 to mice with dextran sodium sulfate (DSS)-induced acute colitis, to explore whether it regulates inflammatory responses in colitis.
Project description:We used a combined transcriptomic and proteomic approach to characterize the venom of a male and female of the black-back scorpion (Hadrurus spadix).
