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      Pilot Investigation of SARS-CoV-2 Variants in the Island of Sicily Prior to and in the Second Wave of the COVID-19 Pandemic

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          Abstract

          After 2 years of the COVID-19 pandemic, we continue to face vital challenges stemming from SARS-CoV-2 variation, causing changes in disease transmission and severity, viral adaptation to animal hosts, and antibody/vaccine evasion. Since the monitoring, characterization, and cataloging of viral variants are important and the existing information on this was scant for Sicily, this pilot study explored viral variants circulation on this island before and in the growth phase of the second wave of COVID-19 (September and October 2020), and in the downslope of that wave (early December 2020) through sequence analysis of 54 SARS-CoV-2-positive samples. The samples were nasopharyngeal swabs collected from Sicilian residents by a state-run one-health surveillance laboratory in Palermo. Variant characterization was based on RT-PCR amplification and sequencing of four regions of the viral genome. The B.1.177 variant was the most prevalent one, strongly predominating before the second wave and also as the wave downsized, although its relative prevalence decreased as other viral variants, particularly B.1.160, contributed to virus circulation. The occurrence of the B.1.160 variant may have been driven by the spread of that variant in continental Europe and by the relaxation of travel restrictions in the summer of 2020. No novel variants were identified. As sequencing of the entire viral genome in Sicily for the period covered here was restricted to seven deposited viral genome sequences, our results shed some light on SARS-CoV-2 variant circulation during that wave in this insular region of Italy which combines its partial insular isolation with being a major entry point for the African immigration.

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          A Novel Coronavirus from Patients with Pneumonia in China, 2019

          Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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            Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

            A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1-3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.
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              Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

              Summary A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                26 April 2022
                2022
                26 April 2022
                : 13
                : 869559
                Affiliations
                [1] 1Department of Pharmacy, Faculty of Health Sciences, Universidad CEU Cardenal Herrera, CEU Universities , Valencia, Spain
                [2] 2Istituto Zooprofilattico Sperimentale della Sicilia “A. Mirri” , Palermo, Italy
                [3] 3Instituto de Biomedicina de Valencia (IBV-CSIC), CIBER of Rare Diseases (CIBERER-ISCIII) , Valencia, Spain
                [4] 4Department of Biomedical Sciences, Faculty of Health Sciences, Universidad CEU Cardenal Herrera, CEU Universities , Valencia, Spain
                [5] 5Department of Medicine, Faculty of Health Sciences, Universidad CEU Cardenal Herrera, CEU Universities , Valencia, Spain
                Author notes

                Edited by: Yi-Wei Tang, Cepheid, United States

                Reviewed by: Ana P. Tedim, Institute of Health Sciences Studies of Castilla y León (IECSCYL), Spain; Francesca Caccuri, University of Brescia, Italy

                *Correspondence: Elisa Maiques, emaiques@ 123456uchceu.es
                Consuelo Rubio-Guerri, consuelo.rubio@ 123456uchceu.es

                These authors have contributed equally to this work

                This article was submitted to Virology, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2022.869559
                9087553
                35558104
                5ea4f0c8-e185-4718-aa79-380855b11c75
                Copyright © 2022 Padilla-Blanco, Gucciardi, Guercio, Rubio, Princiotta, Veses, Terrana, Sheth, Pascual-Ortiz, Maiques, Purpari and Rubio-Guerri.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 February 2022
                : 25 March 2022
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 25, Pages: 8, Words: 5664
                Funding
                Funded by: Agència Valenciana de la Innovació, doi 10.13039/501100016028;
                Award ID: COVID-19-203
                Funded by: Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana, doi 10.13039/501100016386;
                Award ID: GV/2021/163
                Funded by: Agencia Estatal de Investigación, doi 10.13039/501100011033;
                Award ID: PID2020-120322RB-C21
                Funded by: Ministero della Salute, doi 10.13039/501100003196;
                Award ID: IZS SI 03/20 RC
                Funded by: Ministerio de Ciencia e Innovación, doi 10.13039/501100004837;
                Award ID: MCIN/AEI/10.13039/501100011033
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                sars-cov-2,sicily (italy),b.1.160 variant,b.1.177 variant,covid-19 in autumn 2020

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