key: cord-0841134-bh0g2jq0 authors: Rodríguez-Maldonado, Abril Paulina; Vázquez-Pérez, Joel Armando; Cedro-Tanda, Alberto; Taboada, Blanca; Boukadida, Celia; Wong-Arámbula, Claudia; Nuñez-García, Tatiana Ernestina; Cruz-Ortiz, Natividad; Barrera-Badillo, Gisela; Hernández-Rivas, Lucía; López-Martínez, Irma; Mendoza-Vargas, Alfredo; Reyes-Grajeda, Juan Pablo; Alcaraz, Nicolas; Peñaloza-Figueroa, Fernando; Gonzalez-Barrera, Dulibeth; Rangel-DeLeon, Daniel; Herrera-Montalvo, Luis Alonso; Mejía-Nepomuceno, Fidencio; Hernández-Terán, Alejandra; Mújica-Sánchez, Mario; Becerril-Vargas, Eduardo; Martínez-Orozco, José Arturo; Pérez-Padilla, Rogelio; Salas-Hernández, Jorge; Sanchez-Flores, Alejandro; Isa, Pavel; Matías-Florentino, Margarita; Ávila-Ríos, Santiago; Muñoz-Medina, José Esteban; Grajales-Muñiz, Concepción; Salas-Lais, Angel Gustavo; Santos Coy-Arechavaleta, Andrea; Hidalgo-Miranda, Alfredo; Arias, Carlos F.; Ramírez-González, José Ernesto title: Emergence and spread of the potential variant of interest (VOI) B.1.1.519 of SARS-CoV-2 predominantly present in Mexico date: 2021-08-27 journal: Arch Virol DOI: 10.1007/s00705-021-05208-6 sha: a851be0ad1ad3a92a6cf780151fee3c0e766609b doc_id: 841134 cord_uid: bh0g2jq0 SARS-CoV-2 variants emerged in late 2020, and at least three variants of concern (B.1.1.7, B.1.351, and P1) have been reported by WHO. These variants have several substitutions in the spike protein that affect receptor binding; they exhibit increased transmissibility and may be associated with reduced vaccine effectiveness. In the present work, we report 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, that 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 establishment 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 can be defined as a virus with specific genetic mutations that differ from the original virus, in some cases reflecting the adaptation of SARS-CoV-2 to its new 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, the 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 (VOCs) with characteristics that have implications for 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 it is likely to have increased severity, based on hospitalization and fatality rates. Variant B.1.3 51 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 reduced neutralization by convalescent and post-vaccination sera [9] . These SARS-CoV-2 VOCs have acquired some of the same spike protein mutations independently, particularly E484K, N501Y, S477N, and K417T, which have been associated with increased viral transmission and/or decreased sensitivity to antibody neutralization [10] . In Latin America, with the exception of P.1 and P.2 observed in Brazil, no other variants with the potential for rapid expansion have been reported so far [11] . Here, we report the identification of a potential VOI harboring the mutations T478K, P681H, and T732A in the spike protein, within the newly named lineage B. A detailed analysis of the samples from Mexico City indicated that, in November, this variant was present in 17.8% (13/73) of the cases, while in December 2020, this proportion increased to 47.5% (47/99). In January 2021, the variant was detected in 77.5% (138/178) of the cases and by February in 90.9% (349/384). This significant increase in the frequency of B.1.1.519 in Mexico City showed that it outcompeted preexisting variants between October 2020 and February 2021, and this increase was also observed in other regions of the country (Fig. 1) , representing more than 50% of the characterized viruses in some states during the first trimester of 2021. In particular, the variant was highly prevalent in Baja California Sur (51.3%, 20/39), Guerrero This variant has also been detected in 17 countries on all five continents. In the Americas, it has been reported in Canada and the USA, and recently in Brazil, Chile, Aruba, Martinique, and Curazao [12] . However, this variant currently is not predominant in these countries. The overall genome analysis of the viruses in the B.1.1.519 lineage showed the presence of 20 mutations in total, compared to the Wuhan-Hu-1 reference genome sequence (NCBI accession number MN908947). Eleven of these mutations are non-synonymous, and four of them are present in the spike protein. Notably, a T478K mutation is present in the receptor binding domain (RBD), where mutations have been shown to reduce the activity of some monoclonal antibodies [9] . All amino acid and nucleotide changes are listed in Table 1 (Fig. 2) . On the other hand, viruses in the lineage B.1.1.519 are already grouped by the GISAID platform in an independent clade, invariably harboring the three mutations mentioned above. 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 [13] . In a deep mutational scanning of the SARS-CoV-2 receptor binding domain, the T478K mutation did not have a significant effect on folding or binding to human angiotensin-converting enzyme 2 (ACE2) [14] . However, this mutation may be involved in immune evasion, particularly escape from antibody neutralization [15] . The P681H mutation is one of the mutations found in the B. C203T -C222T -C241T -C3037T -ORF1a C3140T P141S C10029T T492I C10954T -A11117G I49V C12789T C14408T P323L ORF1b T19839C -C21306T -C22995A T478K 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 53219/ EpiUp date2 0Janu ary20 21_ eng. pdf? seque nce= 1& isAll owed=y Tracking of variants 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. Virological.org Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization 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 The authors express their gratitude to Vanessa