SARS CoV-2 SPIKE GLYCOPROTEIN MUTATIONS AND CHANGES IN PROTEIN STRUCTURE

Ekrem Akbulut

doi:10.23902/trkjnat.774926

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SARS CoV-2 SPIKE GLYCOPROTEIN MUTATIONS AND CHANGES IN PROTEIN STRUCTURE

Year 2021, Volume: 22 Issue: 1, 23 - 33, 15.04.2021

Ekrem Akbulut

https://doi.org/10.23902/trkjnat.774926

Abstract

Severe Acute Respiratory Syndrome Corona Virus-2 (SARS CoV-2) is a single-stranded positive polarity RNA virus with a high virulence effect. Spike (S) glycoprotein is the outermost component of the SARS CoV-2 virion and is important in the entry of the virus into the cell via the angiotensin converting enzyme 2 (ACE2) receptor. ACE2 plays an important role in the regulation of human blood pressure by converting the vasoconstrictor angiotensin 2 to the vasodilator angiotensin 1-7. In this study, the changes that mutations in Asian isolates may cause in S glycoprotein structure were analyzed and modeled to contribute to drug and vaccine targeting studies. Genome, proteome and mutation analyses were done using bioinformatics tools (MAFFT, MegaX, PSIPRED, MolProbity, PyMoL). Protein modelling was performed using ProMod3. We detected 26 mutations in the S glycoprotein. The changes that these mutations reveal in the general topological and conformational structure of the S glycoprotein may affect the virulence features of SARS CoV-2. It was determined that mutations converted the receptor binding domain (RBD) from down-formation to like-up formation. It is thought that conformational change occurring after mutation in RBD may cause an increase in receptor affinity. These findings could be beneficial for disease prevention of and drug/vaccine development for SARS CoV-2.

Keywords

SARS CoV-2, COVID19, spike protein, mutational changes, protein structure

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Year 2021, Volume: 22 Issue: 1, 23 - 33, 15.04.2021

Ekrem Akbulut

https://doi.org/10.23902/trkjnat.774926

Abstract

Şiddetli akut solunum yolu sendromu koronavirüsü-2 (SARS CoV-2) yüksek virülans etkiye sahip tek zincirli pozitif polariteli RNA virüsüdür. Spike (S) glikoprotein SARS CoV-2 virionunun en dıştaki bileşenidir ve anjiyotensin dönüştürücü enzim 2 (ACE2) reseptörü aracılığı ile virüsün hücreye girişinde önemlidir. ACE2, vazokonstriktör anjiyotensin 2'yi vazodilatör anjiyotensin 1-7'ye dönüştürerek insanda kan basıncının düzenlenmesinde önemli roller üstlenir. Bu çalışmada, Asya izolatlarındaki mutasyonların S glikoprotein yapısında neden olabileceği değişiklikler analiz edilmiş ve ilaç ve aşı hedefleme çalışmalarına katkıda bulunmak üzere modellenmiştir. Genom, proteom ve mutasyon analizleri biyoinformatik araçları (MAFFT, MegaX, PSIPRED, MolProbity, PyMoL) kullanılarak yapıldı. Protein modellemesi ProMod3 kullanılarak yapıldı. S glikoproteinde 26 mutasyon tespit edilmiştir. Bu mutasyonların S glikoproteininin genel topolojik ve konformasyonel yapısında ortaya çıkardığı değişiklikler, SARS CoV-2’nin virülans özelliklerini etkileyebilir. Mutasyonların reseptör bağlanma bölgesini (RBB) kapalı formasyondan açık formasyon benzeri bir yapıya dönüştürdüğü belirlenmiştir. RBB'de mutasyondan sonra meydana gelen konformasyonel değişimin reseptör afinitesinde bir artışa neden olabileceği düşünülmektedir. Bu bulgular hastalığın önlenmesi ve SARS CoV-2 ilaç ve aşı geliştirme çalışmaları için faydalı olabilir.

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Details

Primary Language	English
Subjects	Structural Biology
Journal Section	Research Article/Araştırma Makalesi
Authors	Ekrem Akbulut 0000-0002-7526-9835
Publication Date	April 15, 2021
Submission Date	July 28, 2020
Acceptance Date	November 23, 2020
Published in Issue	Year 2021 Volume: 22 Issue: 1

Cite

APA	Akbulut, E. (2021). SARS CoV-2 SPIKE GLYCOPROTEIN MUTATIONS AND CHANGES IN PROTEIN STRUCTURE. Trakya University Journal of Natural Sciences, 22(1), 23-33. https://doi.org/10.23902/trkjnat.774926
AMA	Akbulut E. SARS CoV-2 SPIKE GLYCOPROTEIN MUTATIONS AND CHANGES IN PROTEIN STRUCTURE. Trakya Univ J Nat Sci. April 2021;22(1):23-33. doi:10.23902/trkjnat.774926
Chicago	Akbulut, Ekrem. “SARS CoV-2 SPIKE GLYCOPROTEIN MUTATIONS AND CHANGES IN PROTEIN STRUCTURE”. Trakya University Journal of Natural Sciences 22, no. 1 (April 2021): 23-33. https://doi.org/10.23902/trkjnat.774926.
EndNote	Akbulut E (April 1, 2021) SARS CoV-2 SPIKE GLYCOPROTEIN MUTATIONS AND CHANGES IN PROTEIN STRUCTURE. Trakya University Journal of Natural Sciences 22 1 23–33.
IEEE	E. Akbulut, “SARS CoV-2 SPIKE GLYCOPROTEIN MUTATIONS AND CHANGES IN PROTEIN STRUCTURE”, Trakya Univ J Nat Sci, vol. 22, no. 1, pp. 23–33, 2021, doi: 10.23902/trkjnat.774926.
ISNAD	Akbulut, Ekrem. “SARS CoV-2 SPIKE GLYCOPROTEIN MUTATIONS AND CHANGES IN PROTEIN STRUCTURE”. Trakya University Journal of Natural Sciences 22/1 (April 2021), 23-33. https://doi.org/10.23902/trkjnat.774926.
JAMA	Akbulut E. SARS CoV-2 SPIKE GLYCOPROTEIN MUTATIONS AND CHANGES IN PROTEIN STRUCTURE. Trakya Univ J Nat Sci. 2021;22:23–33.
MLA	Akbulut, Ekrem. “SARS CoV-2 SPIKE GLYCOPROTEIN MUTATIONS AND CHANGES IN PROTEIN STRUCTURE”. Trakya University Journal of Natural Sciences, vol. 22, no. 1, 2021, pp. 23-33, doi:10.23902/trkjnat.774926.
Vancouver	Akbulut E. SARS CoV-2 SPIKE GLYCOPROTEIN MUTATIONS AND CHANGES IN PROTEIN STRUCTURE. Trakya Univ J Nat Sci. 2021;22(1):23-3.

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