Exploring the SARS-CoV-2 spike protein destabilizer toxin from the scorpion, spider, and wasp group of toxins as a promising candidate for the identification of pharmacophores against viral infections.

Background: The SARS-CoV-2 virus is the infectious agent that causes coronavirus illness (COVID-19). The majority of virus-infected individuals will recover without the need for special care after experiencing mild-to-moderate respiratory symptoms. Some people, nevertheless, will get quite sick and need medical help. The choice of COVID-19 treatment should be made individually. The severity of the illness and the chance that it will worsen will determine the decision. Therefore, developing more potent medications is always a primary goal. Finding more effective drugs is a top priority. In this regard, natural animal toxins, such as toxin derived from scorpions, spiders, and wasps, have been found to include compounds that have significant therapeutic properties. Specifically, targeting the spike protein which acts as a gateway for the vires to enter the human or animal cells. Aim: This study focuses on the ability of toxins to destabilize the spike protein of the SARS-CoV-2 virus, which is responsible for the SARS-CoV-2 pandemic. Methods: The active protein structure of the SARS-CoV-2, the toxins chosen obtained from the RCSB-protein data bank (PDB), and the molecular structures of toxins that were not proteins were either obtained from PubChem or downloaded as computer structure models from RCSB-PDB. Using molecular docking software such as "PyRx," analyzers such as "BIOVIA-Discovery studios" and "Pymol," and various techniques, the evaluation of the interactions between the spike protein and toxin was performed, to find possible pharmacophores that might serve as a foundation for upcoming medication development. The protein-ligand complex was put to test through the molecular dynamic (MD) simulation via visual molecular dynamics /nanoscale molecular dynamics application to determine the complex stability. Results: The current research findings reveal intriguing binding affinities and interaction patterns between the toxin and the SARS-CoV-2 spike protein, where the complex was identified to be stable throughout the study resembling the cellular conditions via MD simulations. We discuss the implications of these interactions and how they might interfere viral infection and entry. Conclusion: The current study sheds light on a promising avenue for the development of antiviral therapies, leveraging natural venoms as a source of inspiration for pharmacophore-based drug discovery opposing viral infections.