key: cord-0776878-8bwkzn7u authors: Rodriguez-Maldonado, A. P.; Vazquez-Perez, J. A.; Cedro-Tanda, A.; Taboada, B.; Boukadida, C.; Wong-Arambula, C.; Nunez-Garcia, T. E.; Cruz-Ortiz, N.; Barrera-Badillo, G.; Hernandez-Rivas, L.; Lopez-Martinez, I.; Mendoza-Vargas, A.; Reyes-Grajeda, J. P.; Alcaraz, N.; Penaloza-Figueroa, F.; Gonzalez-Barrera, D.; Rangel-DeLeon, D.; Herrera-Montalvo, L. A.; Mejia-Nepomuceno, F.; Hernandez-Teran, A.; Mujica-Sanchez, M.; Becerril-Vargas, E.; Martinez-Orozco, J. A.; Perez-Padilla, R.; Salas-Hernandez, J.; Sanchez-Flores, A.; Isa, P.; Matias-Florentino, M.; Avila-Rios, S.; Munoz-Medina, J. E.; Grajal, title: Emergence and spread of the potential variant of interest (VOI) B.1.1.519 predominantly present in Mexico. date: 2021-05-20 journal: nan DOI: 10.1101/2021.05.18.21255620 sha: 5c17a2e1cc8eec2828487356abff4f5bd0c0727e doc_id: 776878 cord_uid: 8bwkzn7u SARS-CoV-2 variants have emerged in late 2020 and there are at least three variants of concern (B.1.1.7, B.1.351, P1) reported by WHO. These variants have several substitutions in the Spike protein that affect receptor binding; they present increased transmissibility and may be associated with reduced vaccine effectiveness. In the present work, we are reporting the identification of a potential variant of interest harboring the mutations T478K, P681H, and T732A in the Spike protein, within the newly named lineage B.1.1.519, which rapidly outcompeted the preexisting variants in Mexico and has been the dominant virus in the country during the first trimester of 2021. Viral mutation is a natural and expected event generated during genomic replication and interaction with the host, resulting in the occurrence of genetic groups also called lineages. The latter differ from each other by specific mutations that accumulate over time, causing the appearance of variants. A variant could be defined as a virus with specific genetic mutations that differ from the original virus, reflecting in some cases SARS-CoV-2 adaptation to its novel human host. Although the majority of mutations in the SARS-CoV-2 genome are expected to be neutral or deleterious, some mutations can confer a selective advantage and may be associated with enhanced fitness, increased infectivity and/or immune evasion [1, 2, 3] . Importantly, the emergence and spread of variants associated with changes in transmission, virulence and/or antigenicity can impact the evolution of the COVID-19 pandemic and might require appropriate public health actions and surveillance [4] . New SARS-CoV-2 variants are spreading rapidly around the world, becoming a public health concern. As of February 23, 2021, Pan-American Health Organization (PAHO)/World Health Organization (WHO) and Global initiative on sharing all influenza data (GISAID) reported the appearance of at least three Variants of Concern (VOC) that have presented characteristics with implication in public health. Variant B.1.1.7 was identified for the first time in the United Kingdom in September 2020 [4, 5] , and by December 2020 it represented 43% of the genomes sequenced, increasing to 82% in January 2021 and to 94% in February 2021 [6]. This variant is of growing concern since it has been shown to be significantly more transmissible than other variants [7] , and to likely have increased severity, based on hospitalization and fatality rates. Variant B.1.351 was detected for the first time in South Africa, in 64% (261 of 411 genomes) of the sequences reported in December 2020, increasing to 75% (99 of 132 genomes) in the next month [6] . Epidemiological data analysis estimated that this VOC is 50% more transmissible than the previous circulating variants. Finally, the P.1 variant was detected for the first time in Brazil in 47% (61 of 130) of the viral genomes in December 2020, increasing to 74% (111 of 150 genomes) in the next month [6, 8] . Of relevance, it has shown a reduced neutralization by convalescent and post-vaccination sera. These SARS-CoV-2 VOCs have independently acquired some of the same Spike protein mutations, particularly E484K, N501Y, S477N, and K417T, which have been associated with increased viral transmission and / or decreased sensitivity to antibody neutralization [9] . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2021. ; https://doi.org/10.1101/2021.05.18.21255620 doi: medRxiv preprint In Latin America, with the exception of P.1 and P.2 observed in Brazil, no other variants with the potential of rapid expansion have been reported so far [10] . Here we report the identification of a potential VOI harboring the mutations T478K, P681H, and T732A in the An "in silico" analysis using different potent structures of related strains, suggested that the position of the T478K mutation in the "S" protein is involved in antibody recognition and the receptor binding site [12] . In a deep mutational scanning of the SARS-CoV-2 receptor binding domain, the T478K mutation did not have a significant effect on folding and human angiotensin-converting enzyme 2 (ACE2) binding [13] . However, this mutation may be involved in immune evasion, particularly escape from antibody neutralization [14] . The . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 20, 2021. ; https://doi.org/10.1101/2021.05.18.21255620 doi: medRxiv preprint Amino acid . Amino acid and nucleotide changes. Main amino acid substitutions are marked in bold . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 20, 2021. ; https://doi.org/10.1101/2021.05.18.21255620 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2021. ; https://doi.org/10.1101/2021.05.18.21255620 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2021. ; https://doi.org/10.1101/2021.05.18.21255620 doi: medRxiv preprint Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus Spike mutation D614G alters SARS-CoV-2 fitness SARS-CoV-2 501Y.V2 variants lack higher infectivity but do have immune escape Occurrence of variants of SARS-CoV-2 in the Americas -20 Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England Genomic characterization of an emergent SARS -CoV-2 lineage in Manaus: preliminary findings A tale of three SARS-CoV-2 variants with independently acquired P681H mutations in New York State A potential SARS-CoV-2 variant of interest (VOI) harboring mutation E484K in the Spike protein was identified within lineage B.1.1.33 circulating in Brazil CoVsurver: Mutation Analysis of hCoV-19 Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization