SARS-CoV-2 Non-Structural Protein 1(NSP1) Mutation Virulence and Natural Selection: Evolutionary Trends in the Six Continents

Salami Ghaleh, S.; Rahimian, K.; Mahmanzar, M.; Mahdavi, B.; Tokhanbigli, S.; Mollapour Sisakht, M.; Farhadi, A.; Mousakhan Bakhtiari, M.; Lee Kuehu, D.; Deng, Y.

doi:10.1101/2022.07.22.501212

bioRxiv · 10.1101/2022.07.22.501212

SARS-CoV-2 Non-Structural Protein 1(NSP1) Mutation Virulence and Natural Selection: Evolutionary Trends in the Six Continents

Salami Ghaleh, S.·Rahimian, K.·Mahmanzar, M.·Mahdavi, B.·Tokhanbigli, S.·Mollapour Sisakht, M.·Farhadi, A.·Mousakhan Bakhtiari, M.·Lee Kuehu, D.·Deng, Y.

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unsegmented positivesense single-stranded RNA virus that belongs to the {beta}-coronavirus. This virus was the cause of a novel severe acute respiratory syndrome in 2019 (COVID-19) that emerged in Wuhan, China at the early stage of the pandemic and rapidly spread around the world. Rapid transmission and reproduction of SARS-CoV-2 threaten worldwide health with a high mortality rate from the virus. According to the significant role of non-structural protein 1 (NSP1) in inhibiting host mRNA translation, this study focuses on the link between amino acid sequences of NSP1 and alterations of them spreading around the world. The SARS-CoV-2 NSP1 protein sequences were analyzed and FASTA files were processed by Python language programming libraries. Reference sequences compared with each NSP1 sample to identify every mutation and categorize them were based on continents and frequencies. NSP1 mutations rate divided into continents were different. Based on continental studies, E87D in global vision and also in Europe notably increased. The E87D mutation has significantly risen especially in the last months of the study as the first frequent mutation observed. The remarkable mutations, H110Y and R24C, have the second and third frequencies, respectively. Based on this mutational information, despite NSP1 being a conserved sequence occurrence, these mutations change the rate of flexibility and stability of the NSP1 protein, which can eventually affect inhibiting the host translation. IMPORTANCEIn this study, we analyzed 6,510,947 sequences of non-structural protein 1 as a conserved region of SARS-CoV-2. According to the obtained results, 93.4819% of samples had no mutant regions on their amino acid sequences. Heat map data of mutational samples demonstrated high percentages of mutations that occurred in the region of 72 to 126 amino acids indicating a hot spot region of the protein. Increased rates of E87D, H110Y, and R24C mutations in the timeline of our study were reported as significant compared to available mutant samples. Analyzing the details of replacing amino acids in the most frequent E87D mutation reveals the role of this alteration in increasing molecule flexibility and destabilizing the structure of the protein.

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Salami Ghaleh, S., Rahimian, K., Mahmanzar, M., Mahdavi, B., Tokhanbigli, S., Mollapour Sisakht, M., Farhadi, A., Mousakhan Bakhtiari, M., Lee Kuehu, D., Deng, Y.. 2022-07-26. SARS-CoV-2 Non-Structural Protein 1(NSP1) Mutation Virulence and Natural Selection: Evolutionary Trends in the Six Continents. https://doi.org/10.1101/2022.07.22.501212

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