Venom Peptides of Echis carinatus against SARS-CoV-2: Effective Inhibition of Human ACE2 Receptor and MPro Spike Protein

Öz

The search for effective inhibitors against SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has led to the exploration of diverse compound libraries. Molecular docking and virtual screening techniques have been employed to identify potential drug candidates. Natural products, known for their wide variety and reduced toxicity, have gained significant attention in these screenings. Snake venom proteins, characterized by their diverse biological activities and unique molecular structures, offer a promising avenue for the discovery of bioactive molecules with therapeutic potential. In this study, we focused on the investigation of snake venom proteins isolated from Echis carinatus, specifically Schistatin (SCH), phospholipase A2 (PLA2), Disintegrin (DS), and Echistatin (ECH) for their potential as inhibitors against SARS-CoV-2. Through molecular docking analysis, the binding interactions between these venom proteins and key SARS-CoV-2 targets, the main protease (Mpro), and the ACE2 receptor were examined. Results revealed that PLA2 exhibited the most favorable binding affinity to both Mpro and ACE2, surpassing the reference drug ritonavir (RTV). SCH, DS, and ECH also demonstrated promising binding affinities with both targets. This study sheds light on the unexplored potential of snake venom proteins, specifically PLA2, SCH, DS, and ECH from E. carinatus venom, as inhibitors against SARS-CoV-2. Further experimental investigations are warranted to validate their antiviral activities and assess their therapeutic potential in combating COVID-19. The exploration of snake venom proteins presents an intriguing avenue for the discovery of novel drug candidates with broad applications in the treatment of various diseases, including viral infections such as COVID-19.

Anahtar Kelimeler

• Venomous snakes
• therapeutic toxins
• protein interactions
• molecular docking

Echis carinatus'un SARS-CoV-2'ye Karşı Venom Peptitleri: İnsan ACE2 Reseptörü ve Mpro Proteininin Etkili İnhibisyonu

Öz

COVID-19 pandemisinden sorumlu virüs olan SARS-CoV-2'ye karşı etkili inhibitör arayışı, çeşitli bileşiklerin keşfedilmesine yol açmıştır. Potansiyel ilaç adaylarını belirlemek için moleküler kenetleme ve sanal tarama teknikleri kullanılmıştır. Geniş çeşitliliği ve düşük toksisitesi ile bilinen doğal ürünler bu analizlerde büyük ilgi görmüştür. Çeşitli biyolojik aktiviteleri ve benzersiz moleküler yapıları ile karakterize edilen yılan zehiri proteinleri, terapötik potansiyele sahip biyoaktif moleküllerin keşfi için umut verici bir yol sunmaktadır. Bu çalışmada, Echis carinatus'tan izole edilen yılan zehri proteinlerinin, özellikle Schistatin (SCH), fosfolipaz A2 (PLA2), Disintegrin (DS) ve Echistatin'in (ECH) SARS-CoV-2'ye karşı inhibitör potansiyelleri açısından araştırılmasına odaklanılmıştır. Moleküler kenetleme analizi yoluyla, bu zehir proteinleri ile ana SARS-CoV-2 hedefleri, ana proteaz (Mpro) ve ACE2 reseptörü arasındaki bağlanma etkileşimleri incelenmiştir. Sonuçlar, PLA2'nin hem Mpro hem de ACE2'ye en uygun bağlanma afinitesini sergileyerek referans ilaç ritonavir'i (RTV) geride bıraktığını ortaya koymuştur. SCH, DS ve ECH ayrıca her iki hedefle umut verici bağlanma afiniteleri göstermiştir. Bu çalışma, yılan zehiri proteinlerinin, özellikle E. carinatus zehrinden elde edilen PLA2, SCH, DS ve ECH'nin SARS-CoV-2'ye karşı inhibitörler olarak keşfedilmemiş potansiyeline ışık tutabileceği görülmüştür. Antiviral aktivitelerini doğrulamak ve COVID-19 ile mücadelede terapötik potansiyellerini değerlendirmek için daha fazla deneysel araştırma yapılması gerekmektedir. Yılan zehri proteinlerinin keşfi, COVID-19 gibi viral enfeksiyonlar da dahil olmak üzere çeşitli hastalıkların tedavisinde geniş uygulamalara sahip yeni ilaç adaylarının keşfi için ilgi çekici bir yol sunmaktadır.

Anahtar Kelimeler

• Zehirli yılanlar
• terapötik toksinler
• protein etkileşimleri
• moleküler kenetleme

Kaynakça

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