Structural and Functional Venomics for Drug Discovery - PDF

The 7th Annual Student Research Conference “Challenges and Creativity: The Role of Artificial Intellige...

The 7th Annual Student Research Conference “Challenges and Creativity: The Role of Artificial Intelligence in Developing Science ” Structural and Functional Venomics as a Powerful Approach for Drug Discovery and Development Amira M. S. Zaghloul, Mariam M. Gerges, Mohamed A. Abdel-Rahman Zoology Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt Graphical Abstract Some potential and approved drugs with their pharmacological properties Animal Teprotide (Captopril®) was the 1st drug Venom Gland developed from snake venom isolated from Angiotensinogen Milking Bothrops jararca. + Renin Venom Venom It is an antihypertensive molecule used to Angiotensin I Bradykinin control blood pressure by inhibiting the Transcriptomics Proteomics angiotensin-converting enzyme (ACE). + ACE + Degradation It is a drug derived from bradykinin- Angiotensin II Inactivated peptide Venomics / Toxinome potentiating peptides. Approved by the FDA in 1981. Have Structure & Function of various derivatives such as enalapril, ramipril, and Vasoconstriction peptides lisinopril[9,10,11,12,13,14,15,16]. New drugs Anticoagulants have many mechanisms. ω-conotoxin-MVIIA isolated Desirudin isolated from saliva of Hirudo from Conus magus which inhibits medicinalis inhibitor of thrombin, Binds with C - the N-type, CaV2.2 subtype of terminus to the active site of thrombin voltage-gated calcium (Cav) preventing thrombin’s activity[15,17,18,19,20,21,22,23]. channels, was commercialized as Introduction / Methodology of Venomics Eptifbatide isolated from Sistrurus miliarius (Prialt®) (Analgesic drug) after from disintegrins, act on αIIbβ3 integrin FDA approval in 2004[28,29,30,31,32]. receptors by KGD-motif[24,25,26,27]. Venomous animals have specialized venom glands, which enable them to deliver potent toxins through various mechanisms. In contrast, poisonous animals lack such glands and instead rely on other means to produce and disseminate poison. The distribution of venomous animals is pervasive, as it spans across various regions and habitats worldwide. Among the thousands of species capable of producing venom and poison, prominent examples include annelids, Bothrops moojeni mollusks, arthropods, and vertebrates[1,2,3,4,5,6]. Binds Platelets Eptifibatide (Integrilin®) Egyptian Natural Resources Melittin is isolated from venom of Apis Venoms & Poisons are mellifera it a pore forming peptide can act Pharmacological Gold Mines as AMPs, Anticancer, and inhibits proinflamatory signals such as Prostaglandin by inhibiting COX-2 (anti-inflammatory)[33,34]. Chlorotoxin (Cltx) isolated from Leiurus quinquestriatus act as Anticancer. Bind to different targets Recent advances in cutting-edge technologies (OMIC's) have allowed including chloride ion channels, for a deeper understanding and clarifying of the structure and potassium channels membrane type-2 Pharmacological efficacy of peptides of animal venom. The integration matrix metalloprotease (MMP-2), and between proteomics & transcriptomics gives us a detailed overview annexin A2 targeting cancer cells on toxinome (full picture of venom)[7,8]. including glioma, melanoma, small- Scorpion venom gland Proteomics cell lung carcinoma[32,35]. Exenatide (Exendin-4) (Byetta®) isolated from venom of Gila monster Heloderma suspectum act as GLP-1 antagonist used in treatment of Type 2 Diabetes Mellitus[23,36,37,38]. Ingestion of food Degrade Incretins (ex. GLP-1) DPP-4  Glucagon  Insulin Some peptides efficacies within therapeutic dose Decrease sugar in blood Antihypertensive Anticoagulant AMPs & Anticancer Anti-inflammatory Analgesic Teprotide Integrilin Scorpine Melittin ω- conotoxin BPPs Tirofiban Chlorotoxin Smp 24 Melittin Cobrotoxin Tetrodotoxin Acknowledgment Rhodostomine BmKCT Smp 43 Echistatin Imperotoxin Hirudin This work is supported by Science, Technology & This has led to the development of some effective drugs for various Innovation Funding Authority (STDF) under the grant incurable disease, alternatives for drugs with nonspecific activities number 45890 (Call 20 / Egypt-US Cooperation Grant). and drugs causing addiction. This work focuses on the new structural and functional findings obtained from venom of terrestrial and marine venomous animals with the aid of Venomics technology. References