ÇOKLU HESAPLAMALI YAKLAŞIMLA ÜÇ SARS-COV-2 İLAÇ HEDEFLERİ ÜZERİNDE SANAL TARAMA VE MOLEKÜLER DOKİNG ANALİZİ

Öz

Amaç: SARS-CoV-2, üst solunum yolu enfeksiyonu ile karakterize pandemik bir virüstür ve hafif semptomlardan ciddi komplikasyonlara kadar gidebilmektedir. Bu durumda, ilaç yeniden kullanım ve bilgisayar destekli çalışmalar, acil çözümler bulmak için çok önemli hale geldi. Bu çalışmada, 8820 ilaç adayının SARS-CoV-2'nin yapısal olmayan üç protein yapısı DrugBank veri tabanından elde edilen ilaç adayları veya ilaç molekülleri ile olan ilaç-hedef etkileşimleri analiz edilmiştir.

Gereç ve Yöntem: DrugBank veri tabanından elde edilen 8820 ilaç molekülü veya ilaç adayının kapsamlı sanal tarama ve moleküler doking çalışmaları, SARS-CoV-2'nin RNA bağlayıcı proteini, 2'-O-metiltransferaz ve endoribonükleaz üzerinde gerçekleştirildi; ve her hedef için potansiyel ilaç adayları belirlendi. Yüksek Verimli Sanal Tarama (HTVS), Standard Precision (SP), Extra Precision (XP) ve Moleküler Mekanik Genelleştirilmiş Doğan Yüzey Alanı (MM-GBSA) ile sanal tarama çalışmaları yapılmıştır. Ayrıca SARS-CoV-2'nin klinik bulguları, bulaşması, patogenezi ve tedavisi hakkında bilgiler de verilmiştir.

Sonuç ve Tartışma: Her ilaç hedefi için potansiyel bileşik önerileri sunuldu. İlaç hedef proteinlerinin aktif bölgelerinin ligandlarla etkileşime girdiği kilit amino asitler hakkında bilgi verildi. Bu çalışmanın SARS-CoV-2 proteinleri üzerinde hedef bazlı ilaç geliştirme çalışmalarında faydalı olması beklenmektedir.

Anahtar Kelimeler

• SARS-CoV-2
• moleküler doking
• sanal tarama
• DrugBank

VIRTUAL SCREENING AND MOLECULAR DOCKING ANALYSIS ON THREE SARS-COV-2 DRUG TARGETS BY MULTIPLE COMPUTATIONAL APPROACH

Öz

Objective: SARS-CoV-2 is a pandemic virus characterized by upper respiratory tract infection and can range from mild symptoms to severe complications. In this case, drug repurposing and computer-aided studies have become very important to find emergency solutions. In this study, drug-target interactions on three nonstructural protein structures of SARS-CoV-2 of 8820 drug candidates or drug molecules obtained from the DrugBank database were analyzed.

Material and Method: Comprehensive virtual screening and molecular docking studies from 8820 drug molecules or candidates obtained from the DrugBank database were performed on the RNA binding protein, 2'-O-methyltransferase, and endoribonuclease of SARS-CoV-2; and potential drug candidates were determined for each target. Virtual screening studies have been done with High-Throughput Virtual Screening (HTVS), Standard Precision (SP), Extra Precision (XP), and Molecular Mechanics Generalized Born Surface Area (MM-GBSA). Also, information about the clinical findings, transmission, pathogenesis, and treatment of SARS-CoV-2 has been given.

Result and Discussion: Drug-target interactions on three nonstructural protein structures of SARS-CoV-2 of 8820 drug candidates or drug molecules obtained from the DrugBank database were analyzed. Potential compound recommendations for each drug target were presented. Information was given about key amino acids where active sites of drug target proteins interact with ligands. This study is expected to be useful in target-based drug development studies on the proteins of SARS-CoV-2.

Anahtar Kelimeler

• SARS-CoV-2
• molecular docking
• virtual screening
• DrugBank

Kaynakça

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