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1.
Sci Rep ; 12(1): 5736, 2022 Apr 06.
Article in English | MEDLINE | ID: covidwho-1778634

ABSTRACT

The aims of this study were to characterize new SARS-CoV-2 genomes sampled all over Italy and to reconstruct the origin and the evolutionary dynamics in Italy and Europe between February and June 2020. The cluster analysis showed only small clusters including < 80 Italian isolates, while most of the Italian strains were intermixed in the whole tree. Pure Italian clusters were observed mainly after the lockdown and distancing measures were adopted. Lineage B and B.1 spread between late January and early February 2020, from China to Veneto and Lombardy, respectively. Lineage B.1.1 (20B) most probably evolved within Italy and spread from central to south Italian regions, and to European countries. The lineage B.1.1.1 (20D) developed most probably in other European countries entering Italy only in the second half of March and remained localized in Piedmont until June 2020. In conclusion, within the limitations of phylogeographical reconstruction, the estimated ancestral scenario suggests an important role of China and Italy in the widespread diffusion of the D614G variant in Europe in the early phase of the pandemic and more dispersed exchanges involving several European countries from the second half of March 2020.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Communicable Disease Control , Europe/epidemiology , Genome, Viral/genetics , Humans , Italy/epidemiology , Phylogeography , SARS-CoV-2/genetics
2.
Nat Commun ; 13(1): 1152, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1730284

ABSTRACT

In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany. From December 2020 to June 2021 this lineage has been detected in 31 countries. Phylogeographic analyses of A.27 sequences obtained from national and international databases reveal a global spread of this lineage through multiple introductions from its inferred origin in Western Africa. Variant A.27 is characterized by a mutational pattern in the spike gene that includes the L18F, L452R and N501Y spike amino acid substitutions found in various variants of concern but lacks the globally dominant D614G. Neutralization assays demonstrate an escape of A.27 from convalescent and vaccine-elicited antibody-mediated immunity. Moreover, the therapeutic monoclonal antibody Bamlanivimab and partially the REGN-COV2 cocktail fail to block infection by A.27. Our data emphasize the need for continued global monitoring of novel lineages because of the independent evolution of new escape mutations.


Subject(s)
COVID-19/immunology , COVID-19/virology , Pandemics , SARS-CoV-2/immunology , Africa, Western/epidemiology , Amino Acid Substitution , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/immunology , Antiviral Agents/pharmacology , COVID-19/transmission , Drug Combinations , Germany/epidemiology , Global Health , Humans , Immune Evasion/genetics , Mutation , Phylogeography , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
3.
Viruses ; 14(2)2022 02 21.
Article in English | MEDLINE | ID: covidwho-1705877

ABSTRACT

Recombination creates mosaic genomes containing regions with mixed ancestry, and the accumulation of such events over time can complicate greatly many aspects of evolutionary inference. Here, we developed a sliding window bootstrap (SWB) method to generate genomic bootstrap (GB) barcodes to highlight the regions supporting phylogenetic relationships. The method was applied to an alignment of 56 sarbecoviruses, including SARS-CoV and SARS-CoV-2, responsible for the SARS epidemic and COVID-19 pandemic, respectively. The SWB analyses were also used to construct a consensus tree showing the most reliable relationships and better interpret hidden phylogenetic signals. Our results revealed that most relationships were supported by just a few genomic regions and confirmed that three divergent lineages could be found in bats from Yunnan: SCoVrC, which groups SARS-CoV related coronaviruses from China; SCoV2rC, which includes SARS-CoV-2 related coronaviruses from Southeast Asia and Yunnan; and YunSar, which contains a few highly divergent viruses recently described in Yunnan. The GB barcodes showed evidence for ancient recombination between SCoV2rC and YunSar genomes, as well as more recent recombination events between SCoVrC and SCoV2rC genomes. The recombination and phylogeographic patterns suggest a strong host-dependent selection of the viral RNA-dependent RNA polymerase. In addition, SARS-CoV-2 appears as a mosaic genome composed of regions sharing recent ancestry with three bat SCoV2rCs from Yunnan (RmYN02, RpYN06, and RaTG13) or related to more ancient ancestors in bats from Yunnan and Southeast Asia. Finally, our results suggest that viral circular RNAs may be key molecules for the mechanism of recombination.


Subject(s)
DNA Barcoding, Taxonomic/methods , Disease Reservoirs/veterinary , Evolution, Molecular , Genomics/methods , Recombination, Genetic , SARS Virus/genetics , SARS-CoV-2/genetics , Animals , China , Chiroptera/virology , Disease Reservoirs/virology , Genome, Viral , Phylogeography
4.
PLoS One ; 17(2): e0263705, 2022.
Article in English | MEDLINE | ID: covidwho-1690715

ABSTRACT

The world is experiencing one of the most severe viral outbreaks in the last few years, the pandemic infection by SARS-CoV-2, the causative agent of COVID-19 disease. As of December 10th 2021, the virus has spread worldwide, with a total number of more than 267 million of confirmed cases (four times more in the last year), and more than 5 million deaths. A great effort has been undertaken to molecularly characterize the virus, track the spreading of different variants across the globe with the aim to understand the potential effects in terms of transmission capability and different fatality rates. Here we focus on the genomic diversity and distribution of the virus in the early stages of the pandemic, to better characterize the origin of COVID-19 and to define the geographical and temporal evolution of genetic clades. By performing a comparative analysis of 75401 SARS-CoV-2 reported sequences (as of December 2020), using as reference the first viral sequence reported in Wuhan in December 2019, we described the existence of 26538 genetic variants, the most frequent clustering into four major clades characterized by a specific geographical distribution. Notably, we found the most frequent variant, the previously reported missense p.Asp614Gly in the S protein, as a single mutation in only three patients, whereas in the large majority of cases it occurs in concomitance with three other variants, suggesting a high linkage and that this variant alone might not provide a significant selective advantage to the virus. Moreover, we evaluated the presence and the distribution in our dataset of the mutations characterizing the so called "british variant", identified at the beginning of 2021, and observed that 9 out of 17 are present only in few sequences, but never in linkage with each other, suggesting a synergistic effect in this new viral strain. In summary, this is a large-scale analysis of SARS-CoV-2 deposited sequences, with a particular focus on the geographical and temporal evolution of genetic clades in the early phase of COVID-19 pandemic.


Subject(s)
Genetic Variation , SARS-CoV-2/genetics , COVID-19/virology , Evolution, Molecular , Genome, Viral , Genomics , Haplotypes , Humans , Mutation , Pandemics , Phylogeny , Phylogeography , Spike Glycoprotein, Coronavirus/genetics
5.
Genome Biol Evol ; 14(2)2022 02 04.
Article in English | MEDLINE | ID: covidwho-1684680

ABSTRACT

The lack of an identifiable intermediate host species for the proximal animal ancestor of SARS-CoV-2, and the large geographical distance between Wuhan and where the closest evolutionary related coronaviruses circulating in horseshoe bats (members of the Sarbecovirus subgenus) have been identified, is fueling speculation on the natural origins of SARS-CoV-2. We performed a comprehensive phylogenetic study on SARS-CoV-2 and all the related bat and pangolin sarbecoviruses sampled so far. Determining the likely recombination events reveals a highly reticulate evolutionary history within this group of coronaviruses. Distribution of the inferred recombination events is nonrandom with evidence that Spike, the main target for humoral immunity, is beside a recombination hotspot likely driving antigenic shift events in the ancestry of bat sarbecoviruses. Coupled with the geographic ranges of their hosts and the sampling locations, across southern China, and into Southeast Asia, we confirm that horseshoe bats, Rhinolophus, are the likely reservoir species for the SARS-CoV-2 progenitor. By tracing the recombinant sequence patterns, we conclude that there has been relatively recent geographic movement and cocirculation of these viruses' ancestors, extending across their bat host ranges in China and Southeast Asia over the last 100 years. We confirm that a direct proximal ancestor to SARS-CoV-2 has not yet been sampled, since the closest known relatives collected in Yunnan shared a common ancestor with SARS-CoV-2 approximately 40 years ago. Our analysis highlights the need for dramatically more wildlife sampling to: 1) pinpoint the exact origins of SARS-CoV-2's animal progenitor, 2) the intermediate species that facilitated transmission from bats to humans (if there is one), and 3) survey the extent of the diversity in the related sarbecoviruses' phylogeny that present high risk for future spillovers.


Subject(s)
Chiroptera/virology , Coronavirus/genetics , Pangolins/virology , Phylogeny , Recombination, Genetic , Animals , Humans , Phylogeography
6.
Viruses ; 14(2)2022 01 18.
Article in English | MEDLINE | ID: covidwho-1625960

ABSTRACT

Bats have been recognized as an exceptional viral reservoir, especially for coronaviruses. At least three bat zoonotic coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) have been shown to cause severe diseases in humans and it is expected more will emerge. One of the major features of CoVs is that they are all highly prone to recombination. An extreme example is the insertion of the P10 gene from reoviruses in the bat CoV GCCDC1, first discovered in Rousettus leschenaultii bats in China. Here, we report the detection of GCCDC1 in four different bat species (Eonycteris spelaea, Cynopterus sphinx, Rhinolophus shameli and Rousettus sp.) in Cambodia. This finding demonstrates a much broader geographic and bat species range for this virus and indicates common cross-species transmission. Interestingly, one of the bat samples showed a co-infection with an Alpha CoV most closely related to RsYN14, a virus recently discovered in the same genus (Rhinolophus) of bat in Yunnan, China, 2020. Taken together, our latest findings highlight the need to conduct active surveillance in bats to assess the risk of emerging CoVs, especially in Southeast Asia.


Subject(s)
Chiroptera/virology , Coronaviridae Infections/veterinary , Coronaviridae/classification , Coronaviridae/genetics , Disease Reservoirs/veterinary , Disease Reservoirs/virology , Phylogeography , Recombination, Genetic , Animals , Cambodia/epidemiology , China/epidemiology , Chiroptera/classification , Coronaviridae/isolation & purification , Coronaviridae Infections/epidemiology , Coronaviridae Infections/transmission , Evolution, Molecular , Genome, Viral , Phylogeny
7.
Mol Biol Evol ; 39(2)2022 02 03.
Article in English | MEDLINE | ID: covidwho-1594013

ABSTRACT

The ongoing SARS (severe acute respiratory syndrome)-CoV (coronavirus)-2 pandemic has exposed major gaps in our knowledge on the origin, ecology, evolution, and spread of animal coronaviruses. Porcine epidemic diarrhea virus (PEDV) is a member of the genus Alphacoronavirus in the family Coronaviridae that may have originated from bats and leads to significant hazards and widespread epidemics in the swine population. The role of local and global trade of live swine and swine-related products in disseminating PEDV remains unclear, especially in developing countries with complex swine production systems. Here, we undertake an in-depth phylogeographic analysis of PEDV sequence data (including 247 newly sequenced samples) and employ an extension of this inference framework that enables formally testing the contribution of a range of predictor variables to the geographic spread of PEDV. Within China, the provinces of Guangdong and Henan were identified as primary hubs for the spread of PEDV, for which we estimate live swine trade to play a very important role. On a global scale, the United States and China maintain the highest number of PEDV lineages. We estimate that, after an initial introduction out of China, the United States acted as an important source of PEDV introductions into Japan, Korea, China, and Mexico. Live swine trade also explains the dispersal of PEDV on a global scale. Given the increasingly global trade of live swine, our findings have important implications for designing prevention and containment measures to combat a wide range of livestock coronaviruses.


Subject(s)
Coronavirus , Porcine epidemic diarrhea virus , Swine Diseases , Animals , China , Pandemics , Phylogeny , Phylogeography , Porcine epidemic diarrhea virus/genetics , Swine , Swine Diseases/epidemiology , United States
8.
PLoS One ; 16(12): e0261229, 2021.
Article in English | MEDLINE | ID: covidwho-1571989

ABSTRACT

In-depth study of the entire SARS-CoV-2 genome has uncovered many mutations, which have replaced the lineage that characterized the first wave of infections all around the world. In December 2020, the outbreak of variant of concern (VOC) 202012/01 (lineage B.1.1.7) in the United Kingdom defined a turning point during the pandemic, immediately posing a worldwide threat on the Covid-19 vaccination campaign. Here, we reported the evolution of B.1.1.7 lineage-related infections, analyzing samples collected from January 1st 2021, until April 15th 2021, in Friuli Venezia Giulia, a northeastern region of Italy. A cohort of 1508 nasopharyngeal swabs was analyzed by High Resolution Melting (HRM) and 479 randomly selected samples underwent Next Generation Sequencing analysis (NGS), uncovering a steady and continuous accumulation of B.1.1.7 lineage-related specimens, joined by sporadic cases of other known lineages (i.e. harboring the Spike glycoprotein p.E484K mutation). All the SARS-CoV-2 genome has been analyzed in order to highlight all the rare mutations that may eventually result in a new variant of interest. This work suggests that a thorough monitoring of the SARS-CoV-2 genome by NGS is essential to contain any new variant that could jeopardize all the efforts that have been made so far to resolve the emergence of the pandemic.


Subject(s)
COVID-19/diagnosis , Nasopharynx/virology , SARS-CoV-2/classification , Sequence Analysis, RNA/methods , COVID-19/epidemiology , Disease Outbreaks , High-Throughput Nucleotide Sequencing , Humans , Italy/epidemiology , Phylogeny , Phylogeography , RNA, Viral/genetics , SARS-CoV-2/genetics , United Kingdom/epidemiology
9.
Nat Commun ; 12(1): 5769, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1447305

ABSTRACT

Distinct SARS-CoV-2 lineages, discovered through various genomic surveillance initiatives, have emerged during the pandemic following unprecedented reductions in worldwide human mobility. We here describe a SARS-CoV-2 lineage - designated B.1.620 - discovered in Lithuania and carrying many mutations and deletions in the spike protein shared with widespread variants of concern (VOCs), including E484K, S477N and deletions HV69Δ, Y144Δ, and LLA241/243Δ. As well as documenting the suite of mutations this lineage carries, we also describe its potential to be resistant to neutralising antibodies, accompanying travel histories for a subset of European cases, evidence of local B.1.620 transmission in Europe with a focus on Lithuania, and significance of its prevalence in Central Africa owing to recent genome sequencing efforts there. We make a case for its likely Central African origin using advanced phylogeographic inference methodologies incorporating recorded travel histories of infected travellers.


Subject(s)
COVID-19/transmission , COVID-19/virology , SARS-CoV-2/genetics , Africa, Central/epidemiology , Antibodies, Neutralizing/immunology , COVID-19/epidemiology , Europe/epidemiology , Humans , Immune Evasion/genetics , Mutation , Phylogeny , Phylogeography , SARS-CoV-2/classification , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Travel/statistics & numerical data
10.
Nature ; 597(7878): 703-708, 2021 09.
Article in English | MEDLINE | ID: covidwho-1442788

ABSTRACT

SARS-CoV-2 infections have surged across the globe in recent months, concomitant with considerable viral evolution1-3. Extensive mutations in the spike protein may threaten the efficacy of vaccines and therapeutic monoclonal antibodies4. Two signature spike mutations of concern are E484K, which has a crucial role in the loss of neutralizing activity of antibodies, and N501Y, a driver of rapid worldwide transmission of the B.1.1.7 lineage. Here we report the emergence of the variant lineage B.1.526 (also known as the Iota variant5), which contains E484K, and its rise to dominance in New York City in early 2021. This variant is partially or completely resistant to two therapeutic monoclonal antibodies that are in clinical use and is less susceptible to neutralization by plasma from individuals who had recovered from SARS-CoV-2 infection or serum from vaccinated individuals, posing a modest antigenic challenge. The presence of the B.1.526 lineage has now been reported in all 50 states in the United States and in many other countries. B.1.526 rapidly replaced earlier lineages in New York, with an estimated transmission advantage of 35%. These transmission dynamics, together with the relative antibody resistance of its E484K sub-lineage, are likely to have contributed to the sharp rise and rapid spread of B.1.526. Although SARS-CoV-2 B.1.526 initially outpaced B.1.1.7 in the region, its growth subsequently slowed concurrently with the rise of B.1.1.7 and ensuing variants.


Subject(s)
COVID-19/virology , SARS-CoV-2/growth & development , SARS-CoV-2/isolation & purification , Antibodies, Neutralizing/immunology , Humans , Mutation , New York/epidemiology , Phylogeny , Phylogeography , Prevalence , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , United States/epidemiology
11.
Nat Commun ; 12(1): 5705, 2021 09 29.
Article in English | MEDLINE | ID: covidwho-1442779

ABSTRACT

COVID-19 transmission rates are often linked to locally circulating strains of SARS-CoV-2. Here we describe 203 SARS-CoV-2 whole genome sequences analyzed from strains circulating in Rwanda from May 2020 to February 2021. In particular, we report a shift in variant distribution towards the emerging sub-lineage A.23.1 that is currently dominating. Furthermore, we report the detection of the first Rwandan cases of the B.1.1.7 and B.1.351 variants of concern among incoming travelers tested at Kigali International Airport. To assess the importance of viral introductions from neighboring countries and local transmission, we exploit available individual travel history metadata to inform spatio-temporal phylogeographic inference, enabling us to take into account infections from unsampled locations. We uncover an important role of neighboring countries in seeding introductions into Rwanda, including those from which no genomic sequences were available. Our results highlight the importance of systematic genomic surveillance and regional collaborations for a durable response towards combating COVID-19.


Subject(s)
COVID-19/virology , Genome, Viral/genetics , SARS-CoV-2/genetics , Travel-Related Illness , Adult , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/transmission , Epidemiological Monitoring , Female , Humans , Male , Phylogeny , Phylogeography , RNA, Viral/genetics , RNA, Viral/isolation & purification , Rwanda/epidemiology , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Whole Genome Sequencing
12.
Infect Genet Evol ; 95: 105038, 2021 11.
Article in English | MEDLINE | ID: covidwho-1433673

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic diversity has the potential to impact the virus transmissibility and the escape from natural infection- or vaccine-elicited neutralizing antibodies. Here, representative samples from circulating SARS-CoV-2 in Colombia between January and April 2021, were processed for genome sequencing and lineage determination following the nanopore amplicon ARTIC network protocol and PANGOLIN pipeline. This strategy allowed us to identify the emergence of the B.1.621 lineage, considered a variant of interest (VOI) with the accumulation of several substitutions affecting the Spike protein, including the amino acid changes I95I, Y144T, Y145S and the insertion 146 N in the N-terminal domain, R346K, E484K and N501Y in the Receptor binding Domain (RBD) and P681H in the S1/S2 cleavage site of the Spike protein. The rapid increase in frequency and fixation in a relatively short time in Magdalena, Atlantico, Bolivar, Bogotá D.C, and Santander that were near the theoretical herd immunity suggests an epidemiologic impact. Further studies will be required to assess the biological and epidemiologic roles of the substitution pattern found in the B.1.621 lineage.


Subject(s)
Amino Acid Substitution , COVID-19/epidemiology , Genome, Viral , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , COVID-19/transmission , COVID-19/virology , Colombia/epidemiology , Epidemiological Monitoring , Evolution, Molecular , High-Throughput Nucleotide Sequencing , Humans , Phylogeny , Phylogeography , Protein Domains , SARS-CoV-2/classification , SARS-CoV-2/pathogenicity , Severity of Illness Index
13.
Viruses ; 13(9)2021 09 10.
Article in English | MEDLINE | ID: covidwho-1411087

ABSTRACT

Uruguay controlled the viral dissemination during the first nine months of the SARS-CoV-2 pandemic. Unfortunately, towards the end of 2020, the number of daily new cases exponentially increased. Herein, we analyzed the country-wide genetic diversity of SARS-CoV-2 between November 2020 and April 2021. We identified that the most prevalent viral variant during the first epidemic wave in Uruguay (December 2020-February 2021) was a B.1.1.28 sublineage carrying Spike mutations Q675H + Q677H, now designated as P.6, followed by lineages P.2 and P.7. P.6 probably arose around November 2020, in Montevideo, Uruguay's capital department, and rapidly spread to other departments, with evidence of further local transmission clusters; it also spread sporadically to the USA and Spain. The more efficient dissemination of lineage P.6 with respect to P.2 and P.7 and the presence of mutations (Q675H and Q677H) in the proximity of the key cleavage site at the S1/S2 boundary suggest that P.6 may be more transmissible than other lineages co-circulating in Uruguay. Although P.6 was replaced by the variant of concern (VOC) P.1 as the predominant lineage in Uruguay since April 2021, the monitoring of the concurrent emergence of Q675H + Q677H in VOCs should be of worldwide interest.


Subject(s)
COVID-19/virology , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , COVID-19/transmission , Genome, Viral , Humans , Mutation , Phylogeography , Retrospective Studies , SARS-CoV-2/pathogenicity , Uruguay
14.
Viruses ; 13(9)2021 09 10.
Article in English | MEDLINE | ID: covidwho-1411077

ABSTRACT

Brazil was considered one of the emerging epicenters of the coronavirus pandemic in 2021, experiencing over 3000 daily deaths caused by the virus at the peak of the second wave. In total, the country had more than 20.8 million confirmed cases of COVID-19, including over 582,764 fatalities. A set of emerging variants arose in the country, some of them posing new challenges for COVID-19 control. The goal of this study was to describe mutational events across samples from Brazilian SARS-CoV-2 sequences publicly obtainable on Global Initiative on Sharing Avian Influenza Data-EpiCoV (GISAID-EpiCoV) platform and to generate indexes of new mutations by each genome. A total of 16,953 SARS-CoV-2 genomes were obtained, which were not proportionally representative of the five Brazilian geographical regions. A comparative sequence analysis was conducted to identify common mutations located at 42 positions of the genome (38 were in coding regions, whereas two were in 5' and two in 3' UTR). Moreover, 11 were synonymous variants, 27 were missense variants, and more than 44.4% were located in the spike gene. Across the total of single nucleotide variations (SNVs) identified, 32 were found in genomes obtained from all five Brazilian regions. While a high genomic diversity has been reported in Europe given the large number of sequenced genomes, Africa has demonstrated high potential for new variants. In South America, Brazil, and Chile, rates have been similar to those found in South Africa and India, providing enough "space" for new mutations to arise. Genomic surveillance is the central key to identifying the emerging variants of SARS-CoV-2 in Brazil and has shown that the country is one of the "hotspots" in the generation of new variants.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Genome, Viral , Mutation , SARS-CoV-2/genetics , Brazil/epidemiology , COVID-19/history , Evolution, Molecular , Genotype , History, 21st Century , Humans , Models, Theoretical , Mutation Rate , Phylogeny , Phylogeography , Public Health Surveillance
15.
J Med Virol ; 93(4): 2010-2020, 2021 04.
Article in English | MEDLINE | ID: covidwho-1384227

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes serious disease in humans. First identified in November/December 2019 in China, it has rapidly spread worldwide. We analyzed 2790 SARS-CoV-2 genome sequences from 56 countries that were available on April 2, 2020, to assess the evolution of the virus during this early phase of its expansion. We aimed to assess sequence variations that had evolved in virus genomes, giving the greatest attention to the S gene. We also aimed to identify haplotypes that the variations may define and consider their geographic and chronologic distribution. Variations at 1930 positions that together cause 1203 amino acid changes were identified. The frequencies of changes normalized to the lengths of genes and encoded proteins were relatively high in ORF3a and relatively low in M. A variation that causes an Asp614Gly near the receptor-binding domain of S were found at a high frequency, and it was considered that this may contribute to the rapid spread of viruses with this variation. Our most important findings relate to haplotypes. Sixty-six haplotypes that constitute thirteen haplotype groups (H1-H13) were identified, and 84.6% of the 2790 sequences analyzed were associated with these haplotypes. The majority of the sequences (75.1%) were associated with haplotype groups H1-H3. The distribution pattern of the haplotype groups differed in various geographic regions. A few were country/territory specific. The location and time of emergence of some haplotypes are discussed. Importantly, nucleotide variations that define the various haplotypes and Tag/signature variations for most of the haplotypes are reported. The practical applications of these variations are discussed.


Subject(s)
COVID-19/virology , Genetic Variation , Genome, Viral , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Evolution, Molecular , Haplotypes , Humans , Phylogeography
16.
Nature ; 597(7878): 703-708, 2021 09.
Article in English | MEDLINE | ID: covidwho-1371602

ABSTRACT

SARS-CoV-2 infections have surged across the globe in recent months, concomitant with considerable viral evolution1-3. Extensive mutations in the spike protein may threaten the efficacy of vaccines and therapeutic monoclonal antibodies4. Two signature spike mutations of concern are E484K, which has a crucial role in the loss of neutralizing activity of antibodies, and N501Y, a driver of rapid worldwide transmission of the B.1.1.7 lineage. Here we report the emergence of the variant lineage B.1.526 (also known as the Iota variant5), which contains E484K, and its rise to dominance in New York City in early 2021. This variant is partially or completely resistant to two therapeutic monoclonal antibodies that are in clinical use and is less susceptible to neutralization by plasma from individuals who had recovered from SARS-CoV-2 infection or serum from vaccinated individuals, posing a modest antigenic challenge. The presence of the B.1.526 lineage has now been reported in all 50 states in the United States and in many other countries. B.1.526 rapidly replaced earlier lineages in New York, with an estimated transmission advantage of 35%. These transmission dynamics, together with the relative antibody resistance of its E484K sub-lineage, are likely to have contributed to the sharp rise and rapid spread of B.1.526. Although SARS-CoV-2 B.1.526 initially outpaced B.1.1.7 in the region, its growth subsequently slowed concurrently with the rise of B.1.1.7 and ensuing variants.


Subject(s)
COVID-19/virology , SARS-CoV-2/growth & development , SARS-CoV-2/isolation & purification , Antibodies, Neutralizing/immunology , Humans , Mutation , New York/epidemiology , Phylogeny , Phylogeography , Prevalence , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , United States/epidemiology
17.
Environ Res ; 204(Pt A): 111909, 2022 03.
Article in English | MEDLINE | ID: covidwho-1364009

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 genomes have been sequenced massively and worldwide and are now available in different public genome repositories. There is much interest in generating bioinformatic tools capable to analyze and interpret SARS-CoV-2 variation. We have designed CovidPhy (http://covidphy.eu), a web interface that can process SARS-CoV-2 genome sequences in plain fasta text format or provided through identity codes from the Global Initiative on Sharing Avian Influenza Data (GISAID) or GenBank. CovidPhy aggregates information available on the large GISAID database (>1.49 M genomes). Sequences are first aligned against the reference sequence and the interface provides different sources of information, including automatic classification of genomes into a pre-computed phylogeny and phylogeographic information, haplogroup/lineage frequencies, and sequencing variation, indicating also if the genome contains known variants of concern (VOC). Additionally, CovidPhy allows searching for variants and haplotypes introduced by the user and includes a list of genomes that are good candidates for being responsible for large outbreaks worldwide, most likely mediated by important superspreading events, indicating their possible geographic epicenters and their relative impact as recorded in the GISAID database.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Genome, Viral , Humans , Pandemics , Phylogeny , Phylogeography
18.
Viruses ; 13(8)2021 08 02.
Article in English | MEDLINE | ID: covidwho-1335237

ABSTRACT

To explore the SARS-CoV-2 pandemic in Algeria, a dataset comprising ninety-five genomes originating from SARS-CoV-2 sampled from Algeria and other countries worldwide, from 24 December 2019, through 4 March 2021, was thoroughly examined. While performing a multi-component analysis regarding the Algerian outbreak, the toolkit of phylogenetic, phylogeographic, haplotype, and genomic analysis were effectively implemented. We estimated the Time to the Most Recent Common Ancestor (TMRCA) in reference to the Algerian pandemic and highlighted the multiple introductions of the disease and the missing data depicted in the transmission loop. In addition, we emphasized the significant role played by local and international travels in disease dissemination. Most importantly, we unveiled mutational patterns, the effect of unique mutations on corresponding proteins, and the relatedness regarding the Algerian sequences to other sequences worldwide. Our results revealed individual amino-acid replacements such as the deleterious replacement A23T in the orf3a gene in Algeria_EPI_ISL_418241. Additionally, a connection between Algeria_EPI_ISL_420037 and sequences originating from the USA was observed through a USA characteristic amino-acid replacement T1004I in the nsp3 gene, found in the aforementioned Algerian sequence. Similarly, successful tracing could be established, such as Algeria/G37318-8849/2020|EPI_ISL_766863, which was imported from Saudi Arabia during the pilgrimage. Lastly, we assessed the Algerian mitigation measures regarding disease containment using statistical analyses.


Subject(s)
COVID-19/virology , Evolution, Molecular , SARS-CoV-2/genetics , Algeria/epidemiology , COVID-19/epidemiology , COVID-19/transmission , Genome, Viral , Genomics , Haplotypes , Humans , Mutation , Pandemics , Phylogeny , Phylogeography , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Saudi Arabia/epidemiology , Travel
19.
Virus Res ; 304: 198526, 2021 10 15.
Article in English | MEDLINE | ID: covidwho-1331290

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses innumerous challenges, like understanding what triggered the emergence of this new human virus, how this RNA virus is evolving or how the variability of viral genome may impact the primary structure of proteins that are targets for vaccine. We analyzed 19471 SARS-CoV-2 genomes available at the GISAID database from all over the world and 3335 genomes of other Coronoviridae family members available at GenBank, collecting SARS-CoV-2 high-quality genomes and distinct Coronoviridae family genomes. Additionally, we analyzed 199,984 spike glycoprotein sequences. Here, we identify a SARS-CoV-2 emerging cluster containing 13 closely related genomes isolated from bat and pangolin that showed evidence of recombination, which may have contributed to the emergence of SARS-CoV-2. The analyzed SARS-CoV-2 genomes presented 9632 single nucleotide variants (SNVs) corresponding to a variant density of 0.3 over the genome, and a clear geographic distribution. SNVs are unevenly distributed throughout the genome and hotspots for mutations were found for the spike gene and ORF 1ab. We describe a set of predicted spike protein epitopes whose variability is negligible. Additionally, all predicted epitopes for the structural E, M and N proteins are highly conserved. The amino acid changes present in the spike glycoprotein of variables of concern (VOCs) comprise between 3.4% and 20.7% of the predicted epitopes of this protein. These results favors the continuous efficacy of the available vaccines targeting the spike protein, and other structural proteins. Multiple epitopes vaccines should sustain vaccine efficacy since at least some of the epitopes present in variability regions of VOCs are conserved and thus recognizable by antibodies.


Subject(s)
COVID-19/virology , Pandemics , SARS-CoV-2 , Animals , COVID-19/epidemiology , Databases, Genetic , Genome, Viral , Humans , Mutation , Phylogeography , SARS-CoV-2/classification , SARS-CoV-2/genetics
20.
Science ; 373(6557): 889-895, 2021 08 20.
Article in English | MEDLINE | ID: covidwho-1322770

ABSTRACT

Understanding the causes and consequences of the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern is crucial to pandemic control yet difficult to achieve because they arise in the context of variable human behavior and immunity. We investigated the spatial invasion dynamics of lineage B.1.1.7 by jointly analyzing UK human mobility, virus genomes, and community-based polymerase chain reaction data. We identified a multistage spatial invasion process in which early B.1.1.7 growth rates were associated with mobility and asymmetric lineage export from a dominant source location, enhancing the effects of B.1.1.7's increased intrinsic transmissibility. We further explored how B.1.1.7 spread was shaped by nonpharmaceutical interventions and spatial variation in previous attack rates. Our findings show that careful accounting of the behavioral and epidemiological context within which variants of concern emerge is necessary to interpret correctly their observed relative growth rates.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , SARS-CoV-2 , COVID-19/prevention & control , COVID-19/transmission , COVID-19 Nucleic Acid Testing , Communicable Disease Control , Genome, Viral , Humans , Incidence , Phylogeography , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Spatio-Temporal Analysis , Travel , United Kingdom/epidemiology
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