ÖZET

Amaç:

Koronavirüs hastalığı-2019 (COVID-19) tedavisi için moleküler docking (kenetlenme) yöntemi ile sedatif, analjezik ve anestezik ilaçların şiddetli akut solunum sendromu koronavirüs 2 (SARS-CoV-2), insan anjiyotensin dönüştürücü enzim-2 (ACE-2) ve SARS-CoV-2- ACE-2 kompleksi üzerindeki inhibitör etkilerinin ve kullanım potansiyelinin araştırılmasıdır.

Gereç ve Yöntem:

Bu çalışmada, COVID-19 tedavisi için klinik testlerde kullanılan ilaçlar (klorokin, hidroksiklorokin ve nelfinavir) ve inhibitör olarak sedasyon, analjezi ve anestezi için en sık kullanılan ilaçlar (desfluran, deksmedetomidin, fentanil, ketamin, midazolam, propofol, remifentanil ve sevofluran) ile üç farklı enzim (6LU7, 1R4L ve 6LZG) arasında moleküler etkileşimi araştırmak için moleküler docking prosedürü uygulanmıştır. Autodock 4.2, Lamarckian Genetik Algoritması, moleküler etkileşim olasılığını analiz etmek için kullanılmıştır. Değerlendirme, Biovia Discovery Studio Visualizer 2020 programı ile yapılmıştır. Moleküler docking sonucunda enzim ile ilaçlar arasında hidrojen-elektrostatik ve van der Waals gibi etkileşim türleri ve şiddetleri tespit edilerek sonuçlar karşılaştırılmıştır.

Bulgular:

Çalışmaya dahil edilen ilaçlar arasında fentanil, SARS-CoV-2, ACE-2 ve SARS-CoV-2- ACE-2 Kompleksi üzerinde çok düşük enerjiyle (-8,75 ile -7,64 kcal/mol) bağlandığı ve bu proteinleri düşük konsantrasyonlarda inhibe etme potansiyeline sahip olduğu görülmüştür. Fentanilden sonra sırasıyla midazolam, ketamin, propofol ve remifentanilin de proteinleri inhibe etme potansiyeline sahip olduğu görülmüştür. Ancak sevofluran ve desfluranın etkisiz olduğu görülmüştür.

Sonuç:

COVID-19 hastalarında uygulanacak sedasyon, analjezi ve anestezi işlemlerinde fentanilin tercih edilebileceğini ve genel anestezi için ise, total intravenöz anestezisinin tercih edilebileceğini düşünüyoruz. Bununla birlikte, bu maddeleri tedavide kullanmak için deneysel ve klinik çalışmalara ihtiyaç vardır.

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Sedatif, Analjezik ve Anestezik İlaçların SARSCoV- 2, ACE-2 ve SARS-CoV-2- ACE-2 Kompleksi ile Etkileşimlerinin Moleküler Yerleştirme Yöntemiyle Araştırılması

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References