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Effects of SARS-CoV-2 Mutations on Protein Structures and Intraviral Protein-Protein Interactions

By Siqi Wu, Chang Tian, Panpan Liu, Dongjie Guo, Wei Zheng, Xiaoqiang Huang, Yang Zhang, Lijun Liu

Posted 16 Aug 2020
bioRxiv DOI: 10.1101/2020.08.15.241349 (published DOI: 10.1002/jmv.26597)

Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) causing coronavirus disease 2019 (COVID-19) has infected ten millions of people across the globe, and massive mutations in virus genome have occurred during the rapid spread of this novel coronavirus. Variance in protein sequence might lead to change in protein structure and interaction, then further affect the viral physiological characteristics, which could bring tremendous influence on the pandemic. In this study, we investigated 18 non-synonymous mutations in SARS-CoV-2 genome which incidence rates were all ≥1% as of July 15th, 2020, then modeled the mutated protein structures and compared them with the reference ones. The results showed that four types of mutations could cause dramatic changes in protein structures (RMSD ≥5.0 Å), which were Q57H and G251V in open reading frames 3a (ORF3a), S194L and R203K/G204R in nucleocapsid (N). Next, we found that these mutations could affect the binding affinity of intraviral protein interactions. In addition, the hot spots within these docking complexes were altered, among which the mutation Q57H was involved in both Orf3a-Orf8 and Orf3a-S protein interactions. Besides, these mutations were widely distributed all over the world, and their occurrences fluctuated as time went on. Notably, the incidences of R203K/G204R in N and Q57H in Orf3a were both over 50% in some countries. Overall, our findings suggest that SARS-CoV-2 mutations can change viral protein structure, binding affinity and hot spots of the interface, thereby may have impacts on SARS-CoV-2 transmission, diagnosis and treatment of COVID-19. ### Competing Interest Statement The authors have declared no competing interest.

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