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      Preliminary report on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Spike mutation T478K

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          Abstract

          Several severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants have emerged, posing a renewed threat to coronavirus disease 2019 containment and to vaccine and drug efficacy. In this study, we analyzed more than 1,000,000 SARS‐CoV‐2 genomic sequences deposited up to April 27, 2021, on the GISAID public repository, and identified a novel T478K mutation located on the SARS‐CoV‐2 Spike protein. The mutation is structurally located in the region of interaction with human receptor ACE2 and was detected in 11,435 distinct cases. We show that T478K has appeared and risen in frequency since January 2021, predominantly in Mexico and the United States, but we could also detect it in several European countries.

          Highlights

          • We analyzed 1,180,571 SARS‐CoV‐2 samples from the public repository GISAID (updated to April 27, 2021).

          • We detected a mutation in SARS‐CoV‐2 Spike (S) protein amino acid 478, S:T478K, which has been growing in sequence in North America (especially Mexico) since January, 2021.

          • S:T478K is one of the characterizing mutations of lineage B.1.1.519, which is currently independent from B.1.1.7 and B.1.351.

          • S:T478K is affecting the Spike binding domain with human receptor ACE2, increasing the electrostatic potential on the interface.

          • Previous experiments show that S:T478K is a possible genetic route for SARS‐CoV‐2 to escape immune recognition.

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          Most cited references25

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          The Protein Data Bank.

          The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.
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            Structural basis of receptor recognition by SARS-CoV-2

            Summary A novel SARS-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans 1,2 . A key to tackling this epidemic is to understand the virus’s receptor recognition mechanism, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor - human ACE2 (hACE2) 3,4 . Here we determined the crystal structure of SARS-CoV-2 receptor-binding domain (RBD) (engineered to facilitate crystallization) in complex of hACE2. Compared with SARS-CoV RBD, a hACE2-binding ridge in SARS-CoV-2 RBD takes a more compact conformation; moreover, several residue changes in SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD/hACE2 interface. These structural features of SARS-CoV-2 RBD enhance its hACE2-binding affinity. Additionally, we showed that RaTG13, a bat coronavirus closely related to SARS-CoV-2, also uses hACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in hACE2 recognition shed light on potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies targeting receptor recognition by SARS-CoV-2.
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              A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology

              The ongoing pandemic spread of a novel human coronavirus, SARS-COV-2, associated with severe pneumonia disease (COVID-19), has resulted in the generation of tens of thousands of virus genome sequences. The rate of genome generation is unprecedented, yet there is currently no coherent nor accepted scheme for naming the expanding phylogenetic diversity of SARS-CoV-2. We present a rational and dynamic virus nomenclature that uses a phylogenetic framework to identify those lineages that contribute most to active spread. Our system is made tractable by constraining the number and depth of hierarchical lineage labels and by flagging and de-labelling virus lineages that become unobserved and hence are likely inactive. By focusing on active virus lineages and those spreading to new locations this nomenclature will assist in tracking and understanding the patterns and determinants of the global spread of SARS-CoV-2.
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                Author and article information

                Contributors
                federico.giorgi@unibo.it
                Journal
                J Med Virol
                J Med Virol
                10.1002/(ISSN)1096-9071
                JMV
                Journal of Medical Virology
                John Wiley and Sons Inc. (Hoboken )
                0146-6615
                1096-9071
                15 May 2021
                : 10.1002/jmv.27062
                Affiliations
                [ 1 ] Department of Pharmacy and Biotechnology University of Bologna Bologna Italy
                Author notes
                [*] [* ] Correspondence Federico M. Giorgi, Department of Pharmacy and Biotechnology, University of Bologna, Via Selmi 3, 40138 Bologna, Italy.

                Email: federico.giorgi@ 123456unibo.it

                Author information
                http://orcid.org/0000-0003-4409-2421
                http://orcid.org/0000-0003-3228-0580
                http://orcid.org/0000-0002-7572-0702
                http://orcid.org/0000-0002-7325-9908
                Article
                JMV27062
                10.1002/jmv.27062
                8242375
                33951211
                f63d6f50-3964-46f2-8e8d-d8c7c23f3c54
                © 2021 Wiley Periodicals LLC

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 02 May 2021
                : 31 March 2021
                : 03 May 2021
                Page count
                Figures: 3, Tables: 2, Pages: 6, Words: 3210
                Funding
                Funded by: Italian Ministry of University and Research
                Award ID: Montalcini
                Categories
                Short Communication
                Short Communications
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:30.06.2021

                Microbiology & Virology
                covid‐19,genomic surveillance,sars‐cov‐2,spike,spike:t478k,s:t478k,t478k
                Microbiology & Virology
                covid‐19, genomic surveillance, sars‐cov‐2, spike, spike:t478k, s:t478k, t478k

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