Olası terapötikler için SARS-CoV-2’nin spike, zarf ve membran proteinlerinin modelleri

Year 2022, Volume: 1 Issue: 3, 133 - 141, 23.12.2022

Gizem Tutkun , Ahmet Ozan Özgen , Uğur Bilge

Abstract

Amaç: Şiddetli akut solunum sendromu ile ilişkili SARS-CoV-2, yüksek morbidite ve mortaliteye sahip, yaygın, hızla büyüyen bir enfeksiyon hastalığıdır. Bu virüsün üç yapısal proteininin dizisindeki mutasyonlar, pandeminin ilerlemesi üzerinde önemli bir etkiye sahip olabilir.

Bu çalışmada, söz konusu SARS-CoV-2'nin beş varyantındaki mutasyonlar modellenip analiz edilerek, gelecekteki ilaç ve aşı araştırmaları için olası hedeflerin ortaya çıkarılması amaçlanmıştır.

Materyal ve Metot: DSÖ tarafından Endişe Verici Varyantlar (VoC) olarak tanımlanan beş varyantın RNA dizileri NCBI'den elde edildi. Bu dizilerin amino asit dizisine çevrilmesi, dizi hizalaması ve varyantlar arasında dizi karşılaştırması, 2020 çalışmasına referansla RStudio 1.4.1717'de gerçekleştirilmiştir.

Wuhan varyantının yapısal proteinleri ve PDB dosyaları, I-TASSER sunucusu ile yapılan çalışmalardan indirildi. Yapısal proteinlerin 3D görüntüleri LLC, Schrödinger, PyMOL Molecular Graphics System 1.2r3pre'de gerçekleştirilmiştir.

Sonuçlar: VoC ve Wuhan soyuna ait üç yapısal proteinin amino asit dizileri ve mutasyonlar gösterilmiştir. Alfa, Beta, Delta ve Gama'daki mutasyon sayıları ise şu şekildeydi; 10, 8, 10 ve 12. Zarf ve zar proteinleri sırasıyla Beta ve Delta'da birer mutasyona sahipti.

Sonuçlar: Sonuçlar, SARS-CoV-2 varyantlarının spike proteinlerinde birkaç mutasyon meydana geldiğini göstermektedir. Zarf ve zar proteinlerinde sadece az sayıda mutasyon gözlenir. Gelecekteki aşı ve ilaç geliştirme çalışmaları için daha az mutasyona uğramış yapısal proteinlere odaklanmak faydalı olabilir.

Keywords

R programlama dili, SARS-CoV-2, Dizi Hizalama, Yapı Proteinleri, Moleküler Modelleme

Models of spike, envelope and membrane proteins of SARS-CoV-2 variants for possible therapeutics

Abstract

Background: SARS-CoV-2 associated with severe acute respiratory syndrome is a common, rapidly growing infectious disease with high morbidity and mortality. Mutations in the sequence of the three structural proteins of this virus may have a significant impact on the progression of the pandemic.

In this study, it was aimed to reveal possible targets for future drug and vaccine research by modeling and analyzing mutations in five variants of SARS-CoV-2 of concern.

Materials and Methods: RNA sequences of five variants identified by WHO as Variants of Concern (VoC) were obtained from NCBI. The translation of these sequences to amino acid sequence, sequence alignment and sequence comparison between variants was performed in RStudio 1.4.1717 with reference to 2020 study. Structural proteins and PDB files of the Wuhan variant were downloaded from studies conducted with the I-TASSER server. 3D representations of structural proteins were performed in LLC, Schrödinger, PyMOL Molecular Graphics System 1.2r3pre.

Results: The amino acid sequences of three structural proteins belonging to the VoC and the Wuhan lineage and the mutations are shown. The mutation numbers in Alpha, Beta, Delta and Gamma were as follows; 10, 8, 10 and 12. The envelope and membrane proteins had one mutation each in Beta and Delta, respectively.

Conclusions: The results show that several mutations occur the spike proteins of the SARS-CoV-2 variants. Only a small number of mutations are observed in envelope and membrane proteins. It may be beficial to focus on less mutated structural proteins for future vaccine and drug development studies. 

Keywords

R programming language, SARS-CoV-2, Sequence alignment, Structural proteins, Molecular modelling

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