Identification of Evolutionary Trajectories Shared across Human Betacoronaviruses.

Comparing the evolution of distantly related viruses can provide insights into common adaptive processes related to shared ecological niches. Phylogenetic approaches, coupled with other molecular evolution tools, can help identify mutations informative on adaptation, although the structural contextualization of these to functional sites of proteins may help gain insight into their biological properties. Two zoonotic betacoronaviruses capable of sustained human-to-human transmission have caused pandemics in recent times (SARS-CoV-1 and SARS-CoV-2), although a third virus (MERS-CoV) is responsible for sporadic outbreaks linked to animal infections. Moreover, two other betacoronaviruses have circulated endemically in humans for decades (HKU1 and OC43). To search for evidence of adaptive convergence between established and emerging betacoronaviruses capable of sustained human-to-human transmission (HKU1, OC43, SARS-CoV-1, and SARS-CoV-2), we developed a methodological pipeline to classify shared nonsynonymous mutations as putatively denoting homoplasy (repeated mutations that do not share direct common ancestry) or stepwise evolution (sequential mutations leading towards a novel genotype). In parallel, we look for evidence of positive selection and draw upon protein structure data to identify potential biological implications. We find 30 candidate mutations, from which 4 (codon sites 18121 [nsp14/residue 28], 21623 [spike/21], 21635 [spike/25], and 23948 [spike/796]; SARS-CoV-2 genome numbering) further display evolution under positive selection and proximity to functional protein regions. Our findings shed light on potential mechanisms underlying betacoronavirus adaptation to the human host and pinpoint common mutational pathways that may occur during establishment of human endemicity.

CurSa: scripts to curate metadata and sample genomes from GISAID for analysis and display in nextstrain and microreact.

The coronavirus SARS-CoV-2 is the most sequenced pathogen ever, with several million genome copies deposited in the GISAID database. This large amount of genomic information poses non-trivial bioinformatic challenges for those interested in studying the evolution of SARS-CoV-2. One common problem when studying the phylogeny of the coronavirus in its geographical context is to count with accurate information of the location of the samples. However, this information is filled by hand by research groups all over the world and sometimes typos and inconsistencies are introduced in the metadata when submitting the sequences to GISAID. Correcting these errors is laborious and time-consuming. Here, we provide a suite of Perl scripts designated to facilitate the curation of this vital information and perform a random sampling of genome sequences if necessary. The scripts provided here can be used to curate geographic information in the metadata and sample the sequences from any country of interest to ease the preparation of files for Nextstrain and Microreact, thus accelerating evolutionary studies of this important pathogen. CurSa scripts are accessible via: https://github.com/luisdelaye/CurSa/.

Molecular In-Depth on the Epidemiological Expansion of SARS-CoV-2 XBB.1.5.

Since the beginning of the pandemic, the generation of new variants periodically recurs. The XBB.1.5 SARS-CoV-2 variant is one of the most recent. This research was aimed at verifying the potential hazard of this new subvariant. To achieve this objective, we performed a genome-based integrative approach, integrating results from genetic variability/phylodynamics with structural and immunoinformatic analyses to obtain as comprehensive a viewpoint as possible. The Bayesian Skyline Plot (BSP) shows that the viral population size reached the plateau phase on 24 November 2022, and the number of lineages peaked at the same time. The evolutionary rate is relatively low, amounting to 6.9 × 10-4 subs/sites/years. The NTD domain is identical for XBB.1 and XBB.1.5 whereas their RBDs only differ for the mutations at position 486, where the Phe (in the original Wuhan) is replaced by a Ser in XBB and XBB.1, and by a Pro in XBB.1.5. The variant XBB.1.5 seems to spread more slowly than sub-variants that have caused concerns in 2022. The multidisciplinary molecular in-depth analyses on XBB.1.5 performed here does not provide evidence for a particularly high risk of viral expansion. Results indicate that XBB.1.5 does not possess features to become a new, global, public health threat. As of now, in its current molecular make-up, XBB.1.5 does not represent the most dangerous variant.

Genomic characterization and molecular evolution of SARS-CoV-2 in Rio Grande do Sul State, Brazil.

SARS-CoV-2 is the virus responsible for the COVID-19 and has afflicted the world since the end of 2019. Different lineages have been discovered and the Gamma lineage, which started the second wave of infections, was first described in Brazil, one of the most affected countries by pandemic. Therefore, this study analyzed SARS-CoV-2 sequenced genomes from Esteio city in Rio Grande do Sul, Southern Brazil. We also comparatively analyzed genomes of the two first years of the pandemic from Rio Grande do Sul state for understanding their genomic and evolutionary patterns. The phylogenomic analysis showed monophyletic groups for Alpha, Gamma, Delta and Omicron, as well as for other circulating lineages in the state. Molecular evolutionary analysis identified several sites under adaptive selection in membrane and nucleocapsid proteins which could be related to a prevalent stabilizing effect on membrane protein structure, as well as majoritarily destabilizing effects on C-terminal nucleocapsid domain.

An overview of viral mutagenesis and the impact on pathogenesis of SARS-CoV-2 variants.

Viruses are submicroscopic, obligate intracellular parasites that carry either DNA or RNA as their genome, protected by a capsid. Viruses are genetic entities that propagate by using the metabolic and biosynthetic machinery of their hosts and many of them cause sickness in the host. The ability of viruses to adapt to different hosts and settings mainly relies on their ability to create de novo variety in a short interval of time. The size and chemical composition of the viral genome have been recognized as important factors affecting the rate of mutations. Coronavirus disease 2019 (Covid-19) is a novel viral disease that has quickly become one of the world's leading causes of mortality, making it one of the most serious public health problems in recent decades. The discovery of new medications to cope with Covid-19 is a difficult and time-consuming procedure, as new mutations represent a serious threat to the efficacy of recently developed vaccines. The current article discusses viral mutations and their impact on the pathogenicity of newly developed variants with a special emphasis on Covid-19. The biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its mutations, pathogenesis, and treatment strategies are discussed in detail along with the statistical data.

Genomic evolution of the Coronaviridae family.

The current outbreak of coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 poses unparalleled challenges to global public health. SARS-CoV-2 is a Betacoronavirus, one of four genera belonging to the Coronaviridae subfamily Orthocoronavirinae. Coronaviridae, in turn, are members of the order Nidovirales, a group of enveloped, positive-stranded RNA viruses. Here we present a systematic phylogenetic and evolutionary study based on protein domain architecture, encompassing the entire proteomes of all Orthocoronavirinae, as well as other Nidovirales. This analysis has revealed that the genomic evolution of Nidovirales is associated with extensive gains and losses of protein domains. In Orthocoronavirinae, the sections of the genomes that show the largest divergence in protein domains are found in the proteins encoded in the amino-terminal end of the polyprotein (PP1ab), the spike protein (S), and many of the accessory proteins. The diversity among the accessory proteins is particularly striking, as each subgenus possesses a set of accessory proteins that is almost entirely specific to that subgenus. The only notable exception to this is ORF3b, which is present and orthologous over all Alphacoronaviruses. In contrast, the membrane protein (M), envelope small membrane protein (E), nucleoprotein (N), as well as proteins encoded in the central and carboxy-terminal end of PP1ab (such as the 3C-like protease, RNA-dependent RNA polymerase, and Helicase) show stable domain architectures across all Orthocoronavirinae. This comprehensive analysis of the Coronaviridae domain architecture has important implication for efforts to develop broadly cross-protective coronavirus vaccines.

Comparative Genomics and Characterization of SARS-CoV-2 P.1 (Gamma) Variant of Concern From Amazonas, Brazil.

BACKGROUND: P.1 lineage (Gamma) was first described in the State of Amazonas, northern Brazil, in the end of 2020, and has emerged as a very important variant of concern (VOC) of SARS-CoV-2 worldwide. P.1 has been linked to increased infectivity, higher mortality, and immune evasion, leading to reinfections and potentially reduced efficacy of vaccines and neutralizing antibodies. METHODS: The samples of 276 patients from the State of Amazonas were sent to a central referral laboratory for sequencing by gold standard techniques, through Illumina MiSeq platform. Both global and regional phylogenetic analyses of the successfully sequenced genomes were conducted through maximum likelihood method. Multiple alignments were obtained including previously obtained unique human SARS-CoV-2 sequences. The evolutionary histories of spike and non-structural proteins from ORF1a of northern genomes were described and their molecular evolution was analyzed for detection of positive (FUBAR, FEL, and MEME) and negative (FEL and SLAC) selective pressures. To further evaluate the possible pathways of evolution leading to the emergence of P.1, we performed specific analysis for copy-choice recombination events. A global phylogenomic analysis with subsampled P.1 and B.1.1.28 genomes was applied to evaluate the relationship among samples. RESULTS: Forty-four samples from the State of Amazonas were successfully sequenced and confirmed as P.1 (Gamma) lineage. In addition to previously described P.1 characteristic mutations, we find evidence of continuous diversification of SARS-CoV-2, as rare and previously unseen P.1 mutations were detected in spike and non-structural protein from ORF1a. No evidence of recombination was found. Several sites were demonstrated to be under positive and negative selection, with various mutations identified mostly in P.1 lineage. According to the Pango assignment, phylogenomic analyses indicate all samples as belonging to the P.1 lineage. CONCLUSION: P.1 has shown continuous evolution after its emergence. The lack of clear evidence for recombination and the positive selection demonstrated for several sites suggest that this lineage emergence resulted mainly from strong evolutionary forces and progressive accumulation of a favorable signature set of mutations.

Phylodynamics reveals the role of human travel and contact tracing in controlling the first wave of COVID-19 in four island nations.

New Zealand, Australia, Iceland, and Taiwan all saw success in controlling their first waves of Coronavirus Disease 2019 (COVID-19). As islands, they make excellent case studies for exploring the effects of international travel and human movement on the spread of COVID-19. We employed a range of robust phylodynamic methods and genome subsampling strategies to infer the epidemiological history of Severe acute respiratory syndrome coronavirus 2 in these four countries. We compared these results to transmission clusters identified by the New Zealand Ministry of Health by contact tracing strategies. We estimated the effective reproduction number of COVID-19 as 1-1.4 during early stages of the pandemic and show that it declined below 1 as human movement was restricted. We also showed that this disease was introduced many times into each country and that introductions slowed down markedly following the reduction of international travel in mid-March 2020. Finally, we confirmed that New Zealand transmission clusters identified via standard health surveillance strategies largely agree with those defined by genomic data. We have demonstrated how the use of genomic data and computational biology methods can assist health officials in characterising the epidemiology of viral epidemics and for contact tracing.

Phylogenomics reveals multiple introductions and early spread of SARS-CoV-2 into Peru.

Peru has become one of the countries with the highest mortality rates from the current coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To investigate early transmission events and the genomic diversity of SARS-CoV-2 isolates circulating in Peru in the early COVID-19 pandemic, we analyzed 3472 viral genomes, of which 149 were from Peru. Phylogenomic analysis revealed multiple and independent introductions of the virus likely from Europe and Asia and a high diversity of genetic lineages circulating in Peru. In addition, we found evidence for community-driven transmission of SARS-CoV-2 as suggested by clusters of related viruses found in patients living in different regions of Peru.

Healthcare workers acquired COVID-19 disease from patients? An investigation by phylogenomics.

The increasing number of coronavirus disease 2019 (COVID-19) cases in the community has posed a significant epidemic pressure on healthcare settings. When healthcare workers (HCWs) acquire COVID-19, contact tracing and epidemiological investigation might not be adequate for determining the source of transmission. Here, we report a phylogenetic investigation involving two infected HCWs and nine patients to determine whether patient-to-HCW transmission had occurred in a hospital without a previous COVID-19 outbreak. This is the first study to apply phylogenomics to investigate suspected nosocomial transmission in a region with low prevalence of COVID-19. Our results do not support the occurrence of direct patient-to-HCW transmission.

Genome-wide comparison of coronaviruses derived from veterinary animals: A canine and feline perspective.

Feline- and canine-derived coronaviruses (FCoVs and CCoVs) are widespread among dog and cat populations. This study was to understand the route of disease origin and viral transmission in veterinary animals and in human through comparative pan-genomic analysis of coronavirus sequences, especially retrieved from genomes of FCoV and CCoV. Average nucleotide identity based on complete genomes might clustered CoV strains according to their infected host, with an exception of type II of CCoV (accession number KC175339) that was clustered closely to virulent FCoVs. In contrast, the hierarchical clustering based on gene repertories retrieved from pan-genome analysis might divided the examined coronaviruses into host-independent clusters, and formed obviously the cluster of Alphacoronaviruses into sub-clusters of feline-canine, only feline, feline-canine-human coronavirus. Also, functional analysis of genomic subsets might help to divide FCoV and CCoV pan-genomes into (i) clusters of core genes encoding spike, membrane, nucleocapsid proteins, and ORF1ab polyprotein; (ii) clusters of core-like genes encoding nonstructural proteins; (iii) clusters of accessory genes encoding the ORF1A; and (iv) two singleton genes encoding nonstructural protein and polyprotein 1ab. Seven clusters of gene repertories were categorized as common to the FCoV and/or CCoV genomes including pantropic and high virulent strains, illustrating that distinct core-like genes/accessory genes concerning to their pathogenicity should be exploited in further biotype analysis of new isolate. In conclusion, the phylogenomic analyses have allowed the identification of trends in the viral genomic data, especially in developing a specific control measures against coronavirus disease, such as the selection of good markers for differentiating new species from common and/or pantropic isolates.

Comparative Genomics and Integrated Network Approach Unveiled Undirected Phylogeny Patterns, Co-mutational Hot Spots, Functional Cross Talk, and Regulatory Interactions in SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in 92 million cases in a span of 1 year. The study focuses on understanding population-specific variations attributing its high rate of infections in specific geographical regions particularly in the United States. Rigorous phylogenomic network analysis of complete SARS-CoV-2 genomes (245) inferred five central clades named a (ancestral), b, c, d, and e (subtypes e1 and e2). Clade d and subclade e2 were found exclusively comprised of U.S. strains. Clades were distinguished by 10 co-mutational combinations in Nsp3, ORF8, Nsp13, S, Nsp12, Nsp2, and Nsp6. Our analysis revealed that only 67.46% of single nucleotide polymorphism (SNP) mutations were at the amino acid level. T1103P mutation in Nsp3 was predicted to increase protein stability in 238 strains except for 6 strains which were marked as ancestral type, whereas co-mutation (P409L and Y446C) in Nsp13 were found in 64 genomes from the United States highlighting its 100% co-occurrence. Docking highlighted mutation (D614G) caused reduction in binding of spike proteins with angiotensin-converting enzyme 2 (ACE2), but it also showed better interaction with the TMPRSS2 receptor contributing to high transmissibility among U.S. strains. We also found host proteins, MYO5A, MYO5B, and MYO5C, that had maximum interaction with viral proteins (nucleocapsid [N], spike [S], and membrane [M] proteins). Thus, blocking the internalization pathway by inhibiting MYO5 proteins which could be an effective target for coronavirus disease 2019 (COVID-19) treatment. The functional annotations of the host-pathogen interaction (HPI) network were found to be closely associated with hypoxia and thrombotic conditions, confirming the vulnerability and severity of infection. We also screened CpG islands in Nsp1 and N conferring the ability of SARS-CoV-2 to enter and trigger zinc antiviral protein (ZAP) activity inside the host cell.IMPORTANCE In the current study, we presented a global view of mutational pattern observed in SARS-CoV-2 virus transmission. This provided a who-infect-whom geographical model since the early pandemic. This is hitherto the most comprehensive comparative genomics analysis of full-length genomes for co-mutations at different geographical regions especially in U.S. strains. Compositional structural biology results suggested that mutations have a balance of opposing forces affecting pathogenicity suggesting that only a few mutations are effective at the translation level. Novel HPI analysis and CpG predictions elucidate the proof of concept of hypoxia and thrombotic conditions in several patients. Thus, the current study focuses the understanding of population-specific variations attributing a high rate of SARS-CoV-2 infections in specific geographical regions which may eventually be vital for the most severely affected countries and regions for sharp development of custom-made vindication strategies.

Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and Other Coronaviruses: A Genome-wide Comparative Annotation and Analysis.

Novel strain of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) causes mild to severe respiratory illness. The early symptoms may be fever, dry cough, sour throat, and difficulty in breathing which may lead to death in severe cases. Compared to previous outbreaks like SARS-CoV and Middle East Respiratory Syndrome (MERS), SARS-CoV2 disease (COVID-19) outbreak has been much distressing due to its high rate of infection but low infection fatality rate (IFR) with 1.4% around the world. World Health Organization (WHO) has declared (COVID-19) a pandemic on March 11, 2020. In the month of January 2020, the whole genome of SARS-CoV2 was sequenced which made work easy for researchers to develop diagnostic kits and to carry out drug repurposing to effectively alleviate the pandemic situation in the world. Now, it is important to understand why this virus has high rate of infectivity or is there any factor involved at the genome level which actually facilitates this virus infection globally? In this study, we have extensively analyzed the whole genomes of different coronaviruses infecting humans and animals in different geographical locations around the world. The main aim of the study is to identify the similarity and the mutational adaptation of the coronaviruses from different host and geographical locations to the SARS-CoV2 and provide a better strategy to understand the mutational rate for specific target-based drug designing. This study is focused to every annotation in a comparative manner which includes SNPs, repeat analysis with the different categorization of the short-sequence repeats and long-sequence repeats, different UTR's, transcriptional factors, and the predicted matured peptides with the specific length and positions on the genomes. The extensive analysis on SNPs revealed that Wuhan SARS-CoV2 and Indian SARS-CoV2 are having only eight SNPs. Collectively, phylogenetic analysis, repeat analysis, and the polymorphism revealed the genomic conserveness within the SARS-CoV2 and few other coronaviruses with very less mutational chances and the huge distance and mutations from the few other species.

VERSO: A comprehensive framework for the inference of robust phylogenies and the quantification of intra-host genomic diversity of viral samples.

We introduce VERSO, a two-step framework for the characterization of viral evolution from sequencing data of viral genomes, which is an improvement on phylogenomic approaches for consensus sequences. VERSO exploits an efficient algorithmic strategy to return robust phylogenies from clonal variant profiles, also in conditions of sampling limitations. It then leverages variant frequency patterns to characterize the intra-host genomic diversity of samples, revealing undetected infection chains and pinpointing variants likely involved in homoplasies. On simulations, VERSO outperforms state-of-the-art tools for phylogenetic inference. Notably, the application to 6,726 amplicon and RNA sequencing samples refines the estimation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution, while co-occurrence patterns of minor variants unveil undetected infection paths, which are validated with contact tracing data. Finally, the analysis of SARS-CoV-2 mutational landscape uncovers a temporal increase of overall genomic diversity and highlights variants transiting from minor to clonal state and homoplastic variants, some of which fall on the spike gene. Available at: https://github.com/BIMIB-DISCo/VERSO.

Genomic Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2, Colombia.

Coronavirus disease (COVID-19) in Colombia was first diagnosed in a traveler arriving from Italy on February 26, 2020. However, limited data are available on the origins and number of introductions of COVID-19 into the country. We sequenced the causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from 43 clinical samples we collected, along with another 79 genome sequences available from Colombia. We investigated the emergence and importation routes for SARS-CoV-2 into Colombia by using epidemiologic, historical air travel, and phylogenetic observations. Our study provides evidence of multiple introductions, mostly from Europe, and documents >12 lineages. Phylogenetic findings validate the lineage diversity, support multiple importation events, and demonstrate the evolutionary relationship of epidemiologically linked transmission chains. Our results reconstruct the early evolutionary history of SARS-CoV-2 in Colombia and highlight the advantages of genome sequencing to complement COVID-19 outbreak investigations.

A Distinct Phylogenetic Cluster of Indian Severe Acute Respiratory Syndrome Coronavirus 2 Isolates.

BACKGROUND: From an isolated epidemic, coronavirus disease 2019 has now emerged as a global pandemic. The availability of genomes in the public domain after the epidemic provides a unique opportunity to understand the evolution and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus across the globe. METHODS: We performed whole-genome sequencing of 303 Indian isolates, and we analyzed them in the context of publicly available data from India. RESULTS: We describe a distinct phylogenetic cluster (Clade I/A3i) of SARS-CoV-2 genomes from India, which encompasses 22% of all genomes deposited in the public domain from India. Globally, approximately 2% of genomes, which to date could not be mapped to any distinct known cluster, fall within this clade. CONCLUSIONS: The cluster is characterized by a core set of 4 genetic variants and has a nucleotide substitution rate of 1.1 × 10-3 variants per site per year, which is lower than the prevalent A2a cluster. Epidemiological assessments suggest that the common ancestor emerged at the end of January 2020 and possibly resulted in an outbreak followed by countrywide spread. To the best of our knowledge, this is the first comprehensive study characterizing this cluster of SARS-CoV-2 in India.

Phylogeography of 27,000 SARS-CoV-2 Genomes: Europe as the Major Source of the COVID-19 Pandemic.

The novel coronavirus SARS-CoV-2 emerged from a zoonotic transmission in China towards the end of 2019, rapidly leading to a global pandemic on a scale not seen for a century. In order to cast fresh light on the spread of the virus and on the effectiveness of the containment measures adopted globally, we used 26,869 SARS-CoV-2 genomes to build a phylogeny with 20,247 mutation events and adopted a phylogeographic approach. We confirmed that the phylogeny pinpoints China as the origin of the pandemic with major founders worldwide, mainly during January 2020. However, a single specific East Asian founder underwent massive radiation in Europe and became the main actor of the subsequent spread worldwide during March 2020. This lineage accounts for the great majority of cases detected globally and even spread back to the source in East Asia. Despite an East Asian source, therefore, the global pandemic was mainly fueled by its expansion across and out of Europe. It seems likely that travel bans established throughout the world in the second half of March helped to decrease the number of intercontinental exchanges, particularly from mainland China, but were less effective between Europe and North America where exchanges in both directions are visible up to April, long after bans were imposed.

Non-synonymous mutations of SARS-CoV-2 leads epitope loss and segregates its variants.

The non-synonymous mutations of SARS-CoV-2 isolated from across the world have been identified during the last few months. The surface glycoprotein spike of SARS-CoV-2 forms the most important hotspot for amino acid alterations followed by the ORF1a/ORF1ab poly-proteins. It is evident that the D614G mutation in spike glycoprotein and P4715L in RdRp is the important determinant of SARS-CoV-2 evolution since its emergence. P4715L in RdRp, G251V in ORF3a and S1498F of Nsp3 is associated with the epitope loss that may influence pathogenesis caused by antibody escape variants. The phylogenomics distinguished the ancestral viral samples from China and most part of Asia, isolated since the initial outbreak and the later evolved variants isolated from Europe and Americas. The evolved variants have been found to predominant globally with the loss of epitopes from its proteins. These have implications for SARS-CoV-2 transmission, pathogenesis and immune interventions.

Genomic Analysis of Early SARS-CoV-2 Variants Introduced in Mexico.

The coronavirus disease 2019 (COVID-19) pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to enabling implementation of effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage A/G, containing mostly sequences from North America, and lineage B/S, containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized 14 independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represented local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described for the country. Within this local transmission cluster, we also identified an H49Y amino acid change in the Spike protein. This mutation represents a homoplasy occurring independently through time and space and may function as a molecular marker to follow any further spread of these viral variants throughout the country. Our results provide a general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts.IMPORTANCE Understanding the introduction, spread, and establishment of SARS-CoV-2 within distinct human populations as well as the evolution of the pandemics is crucial to implement effective control strategies. In this work, we report that the initial virus strains introduced in Mexico came from Europe and the United States and that the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains with a H49Y mutation in the Spike protein, which could be further used as a molecular marker to follow viral spread within the country and the region.