Changes in Interaction Between Accessory Protein 8 and IL-17RA in UK Isolates Caused by Mutations in the SARS-CoV-2 Open Reading Frame 8

Yıl 2021, Cilt: 7 Sayı: 2, 76 - 83, 31.07.2021

Ekrem Akbulut

https://doi.org/10.22399/ijcesen.935624

Öz

SARS-CoV-2 is the infectous agent of Covid-19, one of the most important health problems of the twenty-first century. IL-17RA is an crucial receptor in the generation of the host immune response. ORF8 is the viral accessory protein of SARS-CoV-2 that suppresses the host immune response. Mutations can alter the viral properties and clinical course of SARS-CoV-2. In this study, we investigated the changes that SARS-CoV-2 ORF8 mutations may cause in the interaction of IL-17RA with ORF8. The study was carried out using 825 complete genome sequences from UK isolates. Mutation analyzes were performed using RDP4 and MEGAX. The protein model was created using the Swiss Model. Protein protein interaction was analyzed by Haddock ver 2.4. Analysis of changes in protein stability was performed using SDM2, mCSM stability and DUET tools. The change in ORF8 - IL-17RA binding affinity before and after the mutation was evaluated using mCSM-PPI2. We detected P30S, R52I, Y73C and L118V mutations in SARS-CoV-2 ORF8. Mutations have been shown to reduce protein stability and affinity. After the mutation, the binding dynamics of ORF8 to IL-17RA were changed. Molecular attachment scores were -78.0±3.4 kcal.mol-1 and -76.3±11.9 kcal.mol-1, for wild type and mutant, respectively. After the mutations, the hydrogen bond number and position between ORF8 and IL-17RA changed. While establishing ten hydrogen bonds between the wild type and IL-17RA, four hydrogen bonds were established between the mutant ORF8 and IL-17RA. The decreased affinity between ORF8 and IL-17RA can be seen as a stronger immune response and a milder clinical course. Although our results contain important data for understanding ORF8, which is an important drug target, it needs to be repeated with in-vivo and crystallgraphy studies.

Anahtar Kelimeler

SARS-CoV-2, COVID19, Open Reading Frame 8, Accessory Protein 8, Mutation, IL-17RA

Teşekkür

We gratefully acknowledge the following Authors (See document S1 in Supplementary Material for authors and laboratories that provided genome data used in this study) from the Originating laboratories responsible for obtaining the specimens, as well as the Submitting laboratories where the genome data were generated and shared, on which this research is based. All submitters of data may be contacted directly via www.gisaid.org

Kaynakça

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