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      Mutational landscape of SARS-CoV-2 genome in Turkey and impact of mutations on spike protein structure

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          Abstract

          The Coronavirus Disease 2019 (COVID-19) was declared a pandemic in March 2020 by the World Health Organization (WHO). As of May 25th, 2021 there were 2.059.941 SARS-COV2 genome sequences that have been submitted to the GISAID database, with numerous variations. Here, we aim to analyze the SARS-CoV-2 genome data submitted to the GISAID database from Turkey and to determine the variant and clade distributions by the end of May 2021, in accordance with their appearance timeline. We compared these findings to USA, Europe, and Asia data as well. We have also evaluated the effects of spike protein variations, detected in a group of genome sequences of 13 patients who applied to our clinic, by using 3D modeling algorithms. For this purpose, we analyzed 4607 SARS-CoV-2 genome sequences submitted by different lab centers from Turkey to the GISAID database between March 2020 and May 2021. Described mutations were also introduced in silico to the spike protein structure to analyze their isolated impacts on the protein structure. The most abundant clade was GR followed by G, GH, and GRY and we did not detect any V clade. The most common variant was B.1, followed by B.1.1, and the UK variant, B.1.1.7. Our results clearly show a concordance between the variant distributions, the number of cases, and the timelines of different variant accumulations in Turkey. The 3D simulations indicate an increase in the surface hydrophilicity of the reference spike protein and the detected mutations. There was less surface hydrophilicity increase in the Asp614Gly mutation, which exhibits a more compact conformation around the ACE-2 receptor binding domain region, rendering the structure in a “down” conformation. Our genomic findings can help to model vaccination programs and protein modeling may lead to different approaches for COVID-19 treatment strategies.

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          MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability

          We report a major update of the MAFFT multiple sequence alignment program. This version has several new features, including options for adding unaligned sequences into an existing alignment, adjustment of direction in nucleotide alignment, constrained alignment and parallel processing, which were implemented after the previous major update. This report shows actual examples to explain how these features work, alone and in combination. Some examples incorrectly aligned by MAFFT are also shown to clarify its limitations. We discuss how to avoid misalignments, and our ongoing efforts to overcome such limitations.
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            A new coronavirus associated with human respiratory disease in China

            Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health 1–3 . Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing 4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China 5 . This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.
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              VMD: Visual molecular dynamics

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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draft
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – original draft
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: Formal analysisRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – original draft
                Role: Formal analysisRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – review & editing
                Role: InvestigationRole: Resources
                Role: InvestigationRole: Resources
                Role: InvestigationRole: Resources
                Role: ResourcesRole: Writing – review & editing
                Role: Funding acquisitionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                6 December 2021
                2021
                6 December 2021
                : 16
                : 12
                : e0260438
                Affiliations
                [1 ] Department of Medical Biology, Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul, Turkey
                [2 ] Acibadem Mehmet Ali Aydinlar University Rare Diseases and Orphan Drugs Application and Research Center (ACURARE), Istanbul, Turkey
                [3 ] Department of Biostatistics and Bioinformatics, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey
                [4 ] Department of Medical Biotechnology, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey
                [5 ] Department of Medical Genetics, Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul, Turkey
                [6 ] Department of Genome Studies, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey
                [7 ] Acibadem Labcell Cellular Therapy Laboratory, Istanbul, Turkey
                [8 ] Department of Infectious Diseases and Clinical Microbiology, Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul, Turkey
                University of Hail, SAUDI ARABIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0001-5319-0547
                Article
                PONE-D-21-23553
                10.1371/journal.pone.0260438
                8648120
                34871297
                14f90f55-7ee4-4299-9cb5-06ceee150457
                © 2021 Hatirnaz Ng et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 July 2021
                : 10 November 2021
                Page count
                Figures: 9, Tables: 2, Pages: 21
                Funding
                Funded by: TÜBİTAK 2247-C Trainee Researcher Scholarship Program (STAR)
                Award ID: 2247-C
                Award Recipient :
                Funded by: TÜBİTAK-BIDEB 2244 Industrial Ph.D. Program
                Award ID: 118C082
                Award Recipient :
                Funded by: Acibadem Healthcare Group
                Funded by: Acibadem Mehmet Ali Aydinlar University Research Fund
                Award ID: 2020/02/09
                This project was supported partially by Acibadem Mehmet Ali Aydinlar University Research Fund (ABAPKO, grant number 2020/02/09) and partially by Acibadem Healthcare Group. Sezer Akyoney is funded by TÜBİTAK 2247-C Trainee Researcher Scholarship Program (STAR). Ilayda Sahin is funded by TÜBİTAK-BIDEB 2244 Industrial Ph.D. Program [grant number 118C082].
                Categories
                Research Article
                Biology and life sciences
                Organisms
                Viruses
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                Coronaviruses
                SARS coronavirus
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                Biology and life sciences
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