Evaluation of Receptor Relationships of Some Drugs Used in the Treatment of COVID-19 by Modeling Studies

Abstract

Objective: It is important to investigate the interactions of drugs used in the treatment process of COVID-19 with cellular mechanisms. In this study, the aim was to investigate the interactions of Dexamethasone, Favipiravir, and Hydroxychloroquine drugs used in the treatment of COVID-19 with the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Materials and Methods: Within the scope of the study, firstly, 3-dimensional structures of receptors and drug molecules were formed. Then the interactions of each of the receptor and drug molecules at the binding site were examined by molecular docking studies, which is a computer-aided drug design method, and their binding affinities were evaluated. Results: As a result of the analyses, it was determined that the drug named Hydroxychloroquine has the highest and the drug called Dexamethasone has the lowest binding affinity for all three receptors. In addition, it has been determined that Dexamethasone develops inappropriate interactions with ER and HER2 receptor active site amino acids. Conclusions: In this study, preliminary data on how receptor interactions can occur when normal individuals and breast cancer patients use Dexamethasone, Favipiravir, and Hydroxychloroquine are presented.

Keywords

• Breast cancer
• COVID-19 drugs
• molecular docking
• receptor

COVID-19 Tedavisinde Kullanılan Bazı İlaçların Reseptör İlişkilerinin Modelleme Çalışmaları ile Değerlendirilmesi

Öz

Amaç: COVID-19 tedavi sürecinde kullanılan ilaçların hücresel mekanizmalarla etkileşimlerinin araştırılması önemlidir. Bu çalışmada, COVID-19 tedavisinde kullanılan Deksametazon, Favipiravir ve Hidroksiklorokin adlı ilaçların östrojen reseptörü (ER), progesteron reseptörü (PR) ve insan epidermal büyüme faktörü reseptörü-2 (HER2) ile etkileşimlerinin belirlenmesi hedeflenmiştir. Materyal ve Metot: Çalışma kapsamında, reseptörler ve ilaç moleküllerinin ilk olarak 3-boyutlu yapıları oluşturulmuş, ardından reseptör ve ilaç moleküllerinin her birinin bağlanma bölgesindeki etkileşimleri bilgisayar destekli ilaç tasarım yöntemi olan moleküler kenetlenme çalışmaları ile incelenmiş ve bağlanma afiniteleri değerlendirilmiştir. Bulgular: Yapılan analizler sonucunda, Hidroksiklorokin adlı ilacın her üç reseptöre de en yüksek bağlanma afinitesi gösteren ilaç olduğu ve Deksametazon adlı ilacın ise reseptörlere en düşük afinite ile bağlandığı belirlenmiştir. Ayrıca, Deksametazonun ER ve HER2 reseptör aktif bölge aminoasitleri ile uygun olmayan interaksiyonlar geliştirdiği tespit edilmiştir. Sonuç: Bu çalışmada, normal bireyler ve meme kanseri hastalarının Deksametazon, Favipiravir ve Hidroksiklorokin adlı ilaçları kullanması durumunda reseptör etkileşimlerinin nasıl olabileceğine ilişkin ön veriler sunulmuştur.

Anahtar Kelimeler

• COVID-19 ilaçları
• meme kanseri
• moleküler kenetlenme
• reseptör

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