SARS COV-2 spike XBB. 1.5 varyantının spike protein yapı ve epitop sunumunda ortaya çıkardığı değişimlerin araştırılması

Corona Virus Disease 2019 (COVID19), in which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the etiological agent, is one of the most important health problems of the twenty-first century. SARS-CoV-2, which has caused more than 7 million deaths since its emergence in December 2019, is a positive polarity RNA virus. Spike protein is one of the important drug and vaccine target structures because it binds to the angiotensin converting enzyme-2 (ACE2) receptor during the viral invasion process and activates the cell entry process. Changes in this structure may alter the host immune response and the efficacy of drugs/vaccines. In this context, investigating the changes in protein structure, peptide presentation and protein stability caused by mutations is important for the validity of existing treatment options and the development of new treatment options. In this study, the changes in protein structure, stability and peptide presentation of the SARS CoV-2 spike protein XBB.1.5 (Kraken) variant were investigated using in-silico methods in order to contribute to the development of new and valid therapeutics. The changes in protein three-dimensional structure caused by mutations were modelled by SWISS-MODEL and RoseTTAFold. Changes in protein stability were analysed with mCSM, DDMut, DUET and DynaMut2 and the effects of mutations on protein function were analysed with Provean, SIFT and PolPhen2 tools. Changes in protein dynamic structure were evaluated with elastic network models. The effects of mutations on antigenic determinants were tested using Bepipred Linear, Emini Surface Accessibility and Kolaskar & Tongaonkar antigenicity algorithms. Of the 38 mutations detected in the SARS-CoV-2 XBB.1.5 variant, 22 were found to be in the receptor binding site, which is important in the interaction of the virus with the host cell. Protein stability analyses revealed that 21% of the mutations caused an increase in protein stability while 81% caused an increase in instability (-2.902≤ΔΔG≤+1.82). It was found that 44.7% of the mutations could have detrimental effects on protein function. XBB.1.5. mutations were found to alter the antigenic determinant profile. We found that four highly conserved antigenic determinants that were found to be conserved in many variants were altered in the XBB.1.5 variant. Decreased stability, increased instability and movement appear to result in increased receptor affinity, infectivity and virulence. This study provides a structural framework for understanding the possible effects of alterations caused by SARS-CoV-2 S protein XBB.1.5. mutations on functional properties.