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2.
J Med Virol ; 93(12): 6479-6485, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1530178

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China in early December 2019 has rapidly widespread worldwide. Over the course of the pandemic, due to the advance of whole-genome sequencing technologies, an unprecedented number of genomes have been generated, providing both invaluable insights into the ongoing evolution and epidemiology of the virus and allowing the identification of hundreds of circulating genetic variants during the pandemic. In recent months variants of SARS-CoV-2 that have an increased number of mutations on the Spike protein have brought concern all over the world. These have been called "variants of concerns" (VOCs), and/or "variants of interests" (VOIs) as it has been suggested that their genome mutations might impact transmission, immune control, and virulence. Tracking the spread of emerging SARS-CoV-2 variants is crucial to inform public health efforts and control the ongoing pandemic. In this review, a concise characterization of the SARS-CoV-2 mutational patterns of the main VOCs and VOIs circulating and cocirculating worldwide has been presented to determine the magnitude of the SARS-CoV-2 threat to better understand the virus genetic diversity and its potential impact on vaccination strategy.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , COVID-19 Vaccines/immunology , China/epidemiology , Evolution, Molecular , Genome, Viral/genetics , Humans , Mutation , Mutation Rate , Phylogeny , Spike Glycoprotein, Coronavirus/immunology , Whole Genome Sequencing
3.
PLoS One ; 16(9): e0249254, 2021.
Article in English | MEDLINE | ID: covidwho-1440984

ABSTRACT

Due to the widespread of the COVID-19 pandemic, the SARS-CoV-2 genome is evolving in diverse human populations. Several studies already reported different strains and an increase in the mutation rate. Particularly, mutations in SARS-CoV-2 spike-glycoprotein are of great interest as it mediates infection in human and recently approved mRNA vaccines are designed to induce immune responses against it. We analyzed 1,036,030 SARS-CoV-2 genome assemblies and 30,806 NGS datasets from GISAID and European Nucleotide Archive (ENA) focusing on non-synonymous mutations in the spike protein. Only around 2.5% of the samples contained the wild-type spike protein with no variation from the reference. Among the spike protein mutants, we confirmed a low mutation rate exhibiting less than 10 non-synonymous mutations in 99.6% of the analyzed sequences, but the mean and median number of spike protein mutations per sample increased over time. 5,472 distinct variants were found in total. The majority of the observed variants were recurrent, but only 21 and 14 recurrent variants were found in at least 1% of the mutant genome assemblies and NGS samples, respectively. Further, we found high-confidence subclonal variants in about 2.6% of the NGS data sets with mutant spike protein, which might indicate co-infection with various SARS-CoV-2 strains and/or intra-host evolution. Lastly, some variants might have an effect on antibody binding or T-cell recognition. These findings demonstrate the continuous importance of monitoring SARS-CoV-2 sequences for an early detection of variants that require adaptations in preventive and therapeutic strategies.


Subject(s)
COVID-19/virology , Genome, Viral , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Antibodies/immunology , COVID-19/prevention & control , COVID-19/transmission , High-Throughput Nucleotide Sequencing , Humans , Mutation Rate , Pandemics , Protein Domains , SARS-CoV-2/chemistry , Spike Glycoprotein, Coronavirus/chemistry , T-Lymphocytes/immunology
4.
Virus Res ; 305: 198551, 2021 11.
Article in English | MEDLINE | ID: covidwho-1440397

ABSTRACT

Samples from complete genomes of SARS-CoV-2 isolated during the first wave (December 2019-July 2020) of the global COVID-19 pandemic from 21 countries (Asia, Europe, Middle East and America) around the world, were analyzed using the phylogenetic method with molecular clock dating. Results showed that the first cases of COVID-19 in the human population appeared in the period between July and November 2019 in China. The spread of the virus into other countries of the world began in the autumn of 2019. In mid-February 2020, the virus appeared in all the countries we analyzed. During this time, the global population of SARS-CoV-2 was characterized by low levels of the genetic polymorphism, making it difficult to accurately assess the pathways of infection. The rate of evolution of the coding region of the SARS-CoV-2 genome equal to 7.3 × 10-4 (5.95 × 10-4-8.68 × 10-4) nucleotide substitutions per site per year is comparable to those of other human RNA viruses (Measles morbillivirus, Rubella virus, Enterovirus C). SARS-CoV-2 was separated from its known close relative, the bat coronavirus RaTG13 of the genus Betacoronavirus, approximately 15-43 years ago (the end of the 20th century).


Subject(s)
COVID-19/epidemiology , Evolution, Molecular , Genome, Viral , Mutation Rate , SARS-CoV-2/genetics , Animals , Asia/epidemiology , COVID-19/history , COVID-19/transmission , COVID-19/virology , Chiroptera/virology , Europe/epidemiology , Genomics/methods , History, 20th Century , History, 21st Century , Humans , Middle East/epidemiology , North America/epidemiology , Phylogeny , Polymorphism, Genetic , SARS-CoV-2/classification , SARS-CoV-2/pathogenicity , South America/epidemiology
5.
Viruses ; 13(9)2021 09 21.
Article in English | MEDLINE | ID: covidwho-1427003

ABSTRACT

The error rate displayed during template copying to produce viral RNA progeny is a biologically relevant parameter of the replication complexes of viruses. It has consequences for virus-host interactions, and it represents the first step in the diversification of viruses in nature. Measurements during infections and with purified viral polymerases indicate that mutation rates for RNA viruses are in the range of 10-3 to 10-6 copying errors per nucleotide incorporated into the nascent RNA product. Although viruses are thought to exploit high error rates for adaptation to changing environments, some of them possess misincorporation correcting activities. One of them is a proofreading-repair 3' to 5' exonuclease present in coronaviruses that may decrease the error rate during replication. Here we review experimental evidence and models of information maintenance that explain why elevated mutation rates have been preserved during the evolution of RNA (and some DNA) viruses. The models also offer an interpretation of why error correction mechanisms have evolved to maintain the stability of genetic information carried out by large viral RNA genomes such as the coronaviruses.


Subject(s)
Genome, Viral , Mutation , RNA Virus Infections/virology , RNA Viruses/genetics , RNA, Viral , Animals , Biological Evolution , Coronavirus/genetics , Exonucleases/metabolism , Genetic Variation , Humans , Mutation Rate , Virus Replication
6.
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
7.
Am J Clin Pathol ; 156(4): 634-643, 2021 Sep 08.
Article in English | MEDLINE | ID: covidwho-1408305

ABSTRACT

OBJECTIVES: Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are a group of rare and heterogeneous hematopoietic disorders that frequently present a diagnostic challenge. Here we present our institutional experience with next-generation sequencing (NGS), together with morphologic, flow cytometric, and cytogenetic evaluation, in the diagnosis of MDS/MPN, with particular emphasis on MDS/MPN unclassifiable (MPN-U). METHODS: We evaluated the morphologic, flow cytometric, cytogenetic, and molecular characteristics of all MDS/MPN cases that underwent NGS at our institution between April 2016 and February 2019. RESULTS: Thirty-seven cases of MDS/MPN were identified, including 14 cases of MDS/MPN-U. Ninety-seven percent harbored mutations and immunophenotypic aberrancies (36/37), while only 38% had cytogenetic abnormalities (12/32). The MDS/MPN-U group had the highest rate of myeloblast phenotypic abnormalities and had a high mutation rate of approximately 2.7 mutated genes per case, most commonly in JAK2, SRSF2, and ASXL1. CONCLUSIONS: No single ancillary study was abnormal in every case, but all cases had at least one abnormal finding, demonstrating the usefulness of a multiparameter approach to the diagnosis of MDS/MPN. Although a few specific mutations were found exclusively in MDS/MPN-U and JAK2 mutations were most prevalent, larger studies are needed to determine whether MDS/MPN-U has a mutational "fingerprint," which may aid in diagnosis and targeted therapy.


Subject(s)
Myelodysplastic-Myeloproliferative Diseases/diagnosis , Myeloproliferative Disorders/diagnosis , Adult , Aged , Aged, 80 and over , Cytogenetics , Female , Flow Cytometry , Granulocyte Precursor Cells/pathology , High-Throughput Nucleotide Sequencing , Humans , Immunophenotyping , Male , Middle Aged , Mutation , Mutation Rate , Myelodysplastic-Myeloproliferative Diseases/classification , Myelodysplastic-Myeloproliferative Diseases/genetics , Myelodysplastic-Myeloproliferative Diseases/pathology , Myeloproliferative Disorders/classification , Myeloproliferative Disorders/genetics , Myeloproliferative Disorders/pathology , Sequence Analysis, DNA , Young Adult
8.
J Med Virol ; 94(1): 310-317, 2022 01.
Article in English | MEDLINE | ID: covidwho-1400938

ABSTRACT

SARS-CoV-2 is a newly discovered beta coronavirus at the end of 2019, which is highly pathogenic and poses a serious threat to human health. In this paper, 1875 SARS-CoV-2 whole genome sequences and the sequence coding spike protein (S gene) sampled from the United States were used for bioinformatics analysis to study the molecular evolutionary characteristics of its genome and spike protein. The MCMC method was used to calculate the evolution rate of the whole genome sequence and the nucleotide mutation rate of the S gene. The results showed that the nucleotide mutation rate of the whole genome was 6.677 × 10-4 substitution per site per year, and the nucleotide mutation rate of the S gene was 8.066 × 10-4 substitution per site per year, which was at a medium level compared with other RNA viruses. Our findings confirmed the scientific hypothesis that the rate of evolution of the virus gradually decreases over time. We also found 13 statistically significant positive selection sites in the SARS-CoV-2 genome. In addition, the results showed that there were 101 nonsynonymous mutation sites in the amino acid sequence of S protein, including seven putative harmful mutation sites. This paper has preliminarily clarified the evolutionary characteristics of SARS-CoV-2 in the United States, providing a scientific basis for future surveillance and prevention of virus variants.


Subject(s)
COVID-19/epidemiology , Evolution, Molecular , Genome, Viral/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Amino Acid Sequence/genetics , COVID-19/pathology , Computational Biology , Humans , Mutation Rate , United States/epidemiology , Whole Genome Sequencing
9.
Sci Rep ; 11(1): 17755, 2021 09 07.
Article in English | MEDLINE | ID: covidwho-1397900

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease has spread globally, causing more than 161.5 million cases and 3.3 million deaths to date. Surveillance and monitoring of new mutations in the virus' genome are crucial to our understanding of the adaptation of SARS-CoV-2. Moreover, how the temporal dynamics of these mutations is influenced by control measures and non-pharmaceutical interventions (NPIs) is poorly understood. Using 1,058,020 SARS-CoV-2 from sequenced COVID-19 cases from 98 countries (totaling 714 country-month combinations), we perform a normalization by COVID-19 cases to calculate the relative frequency of SARS-CoV-2 mutations and explore their dynamics over time. We found 115 mutations estimated to be present in more than 3% of global COVID-19 cases and determined three types of mutation dynamics: high-frequency, medium-frequency, and low-frequency. Classification of mutations based on temporal dynamics enable us to examine viral adaptation and evaluate the effects of implemented control measures in virus evolution during the pandemic. We showed that medium-frequency mutations are characterized by high prevalence in specific regions and/or in constant competition with other mutations in several regions. Finally, taking N501Y mutation as representative of high-frequency mutations, we showed that level of control measure stringency negatively correlates with the effective reproduction number of SARS-CoV-2 with high-frequency or not-high-frequency and both follows similar trends in different levels of stringency.


Subject(s)
COVID-19/epidemiology , Communicable Disease Control/standards , Pandemics/prevention & control , SARS-CoV-2/genetics , COVID-19/prevention & control , COVID-19/transmission , COVID-19/virology , Genome, Viral , Global Burden of Disease , Humans , Mutation Rate , Prevalence , SARS-CoV-2/pathogenicity
11.
Int J Antimicrob Agents ; 57(2): 106272, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1385674

ABSTRACT

INTRODUCTION: Genomic alterations in a viral genome can lead to either better or worse outcome and identifying these mutations is of utmost importance. Here, we correlated protein-level mutations in the SARS-CoV-2 virus to clinical outcome. METHODS: Mutations in viral sequences from the GISAID virus repository were evaluated by using "hCoV-19/Wuhan/WIV04/2019" as the reference. Patient outcomes were classified as mild disease, hospitalization and severe disease (death or documented treatment in an intensive-care unit). Chi-square test was applied to examine the association between each mutation and patient outcome. False discovery rate was computed to correct for multiple hypothesis testing and results passing FDR cutoff of 5% were accepted as significant. RESULTS: Mutations were mapped to amino acid changes for 3,733 non-silent mutations. Mutations correlated to mild outcome were located in the ORF8, NSP6, ORF3a, NSP4, and in the nucleocapsid phosphoprotein N. Mutations associated with inferior outcome were located in the surface (S) glycoprotein, in the RNA dependent RNA polymerase, in ORF3a, NSP3, ORF6 and N. Mutations leading to severe outcome with low prevalence were found in the ORF3A and in NSP7 proteins. Four out of 22 of the most significant mutations mapped onto a 10 amino acid long phosphorylated stretch of N indicating that in spite of obvious sampling restrictions the approach can find functionally relevant sites in the viral genome. CONCLUSIONS: We demonstrate that mutations in the viral genes may have a direct correlation to clinical outcome. Our results help to quickly identify SARS-CoV-2 infections harboring mutations related to severe outcome.


Subject(s)
COVID-19/drug therapy , COVID-19/etiology , Mutation , SARS-CoV-2/genetics , Coronavirus Nucleocapsid Proteins/genetics , Female , Hospitalization , Humans , Male , Mutation Rate , Viral Nonstructural Proteins/genetics , Viral Proteins/genetics , Viroporin Proteins/genetics
12.
Arch Virol ; 166(3): 801-812, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1384461

ABSTRACT

Accumulation of mutations within the genome is the primary driving force in viral evolution within an endemic setting. This inherent feature often leads to altered virulence, infectivity and transmissibility, and antigenic shifts to escape host immunity, which might compromise the efficacy of vaccines and antiviral drugs. Therefore, we carried out a genome-wide analysis of circulating SARS-CoV-2 strains to detect the emergence of novel co-existing mutations and trace their geographical distribution within India. Comprehensive analysis of whole genome sequences of 837 Indian SARS-CoV-2 strains revealed the occurrence of 33 different mutations, 18 of which were unique to India. Novel mutations were observed in the S glycoprotein (6/33), NSP3 (5/33), RdRp/NSP12 (4/33), NSP2 (2/33), and N (1/33). Non-synonymous mutations were found to be 3.07 times more prevalent than synonymous mutations. We classified the Indian isolates into 22 groups based on their co-existing mutations. Phylogenetic analysis revealed that the representative strains of each group were divided into various sub-clades within their respective clades, based on the presence of unique co-existing mutations. The A2a clade was found to be dominant in India (71.34%), followed by A3 (23.29%) and B (5.36%), but a heterogeneous distribution was observed among various geographical regions. The A2a clade was highly predominant in East India, Western India, and Central India, whereas the A2a and A3 clades were nearly equal in prevalence in South and North India. This study highlights the divergent evolution of SARS-CoV-2 strains and co-circulation of multiple clades in India. Monitoring of the emerging mutations will pave the way for vaccine formulation and the design of antiviral drugs.


Subject(s)
COVID-19/virology , Genetic Variation/genetics , Genome, Viral/genetics , SARS-CoV-2/genetics , Evolution, Molecular , Geography , Humans , India/epidemiology , Mutation/genetics , Mutation Rate , Phylogeny , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Silent Mutation/genetics , Whole Genome Sequencing
13.
PLoS One ; 15(8): e0238490, 2020.
Article in English | MEDLINE | ID: covidwho-1388885

ABSTRACT

SARS-CoV-2 is still rampaging throughout the world while the many evolutionary studies on it are simultaneously springing up. Researchers have simply utilized the public RNA-seq data to find out the so-called SNPs in the virus genome. The evolutionary analyses were largely based on these mutations. Here, we claim that we reliably detected A-to-G RNA modifications in the RNA-seq data of SARS-CoV-2 with high signal to noise ratios, presumably caused by the host's deamination enzymes. Intriguingly, since SARS-CoV-2 is an RNA virus, it is technically impossible to distinguish SNPs and RNA modifications from the RNA-seq data alone without solid evidence, making it difficult to tell the evolutionary patterns behind the mutation spectrum. Researchers should clarify their biological significance before they automatically regard the mutations as SNPs or RNA modifications. This is not a problem for DNA organisms but should be seriously considered when we are investigating the RNA viruses.


Subject(s)
Betacoronavirus/genetics , Evolution, Molecular , Polymorphism, Single Nucleotide , RNA, Viral/genetics , Base Sequence , COVID-19 , Coronavirus Infections , Humans , Mutation Rate , Pandemics , Pneumonia, Viral , RNA-Seq , SARS-CoV-2
15.
Genome Biol Evol ; 13(10)2021 10 01.
Article in English | MEDLINE | ID: covidwho-1370777

ABSTRACT

Owing to a lag between a deleterious mutation's appearance and its selective removal, gold-standard methods for mutation rate estimation assume no meaningful loss of mutations between parents and offspring. Indeed, from analysis of closely related lineages, in SARS-CoV-2, the Ka/Ks ratio was previously estimated as 1.008, suggesting no within-host selection. By contrast, we find a higher number of observed SNPs at 4-fold degenerate sites than elsewhere and, allowing for the virus's complex mutational and compositional biases, estimate that the mutation rate is at least 49-67% higher than would be estimated based on the rate of appearance of variants in sampled genomes. Given the high Ka/Ks one might assume that the majority of such intrahost selection is the purging of nonsense mutations. However, we estimate that selection against nonsense mutations accounts for only ∼10% of all the "missing" mutations. Instead, classical protein-level selective filters (against chemically disparate amino acids and those predicted to disrupt protein functionality) account for many missing mutations. It is less obvious why for an intracellular parasite, amino acid cost parameters, notably amino acid decay rate, is also significant. Perhaps most surprisingly, we also find evidence for real-time selection against synonymous mutations that move codon usage away from that of humans. We conclude that there is common intrahost selection on SARS-CoV-2 that acts on nonsense, missense, and possibly synonymous mutations. This has implications for methods of mutation rate estimation, for determining times to common ancestry and the potential for intrahost evolution including vaccine escape.


Subject(s)
COVID-19/virology , Mutation , SARS-CoV-2/genetics , Codon Usage , Codon, Nonsense , Evolution, Molecular , Humans , Models, Genetic , Mutation Rate , Mutation, Missense , Polymorphism, Single Nucleotide , Selection, Genetic , Silent Mutation
16.
Brief Bioinform ; 22(2): 1065-1075, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1343662

ABSTRACT

The analysis of the SARS-CoV-2 genome datasets has significantly advanced our understanding of the biology and genomic adaptability of the virus. However, the plurality of advanced sequencing datasets-such as short and long reads-presents a formidable computational challenge to uniformly perform quantitative, variant or phylogenetic analysis, thus limiting its application in public health laboratories engaged in studying epidemic outbreaks. We present a computational tool, Infectious Pathogen Detector (IPD), to perform integrated analysis of diverse genomic datasets, with a customized analytical module for the SARS-CoV-2 virus. The IPD pipeline quantitates individual occurrences of 1060 pathogens and performs mutation and phylogenetic analysis from heterogeneous sequencing datasets. Using IPD, we demonstrate a varying burden (5.055-999655.7 fragments per million) of SARS-CoV-2 transcripts across 1500 short- and long-read sequencing SARS-CoV-2 datasets and identify 4634 SARS-CoV-2 variants (~3.05 variants per sample), including 449 novel variants, across the genome with distinct hotspot mutations in the ORF1ab and S genes along with their phylogenetic relationships establishing the utility of IPD in tracing the genome isolates from the genomic data (as accessed on 11 June 2020). The IPD predicts the occurrence and dynamics of variability among infectious pathogens-with a potential for direct utility in the COVID-19 pandemic and beyond to help automate the sequencing-based pathogen analysis and in responding to public health threats, efficaciously. A graphical user interface (GUI)-enabled desktop application is freely available for download for the academic users at http://www.actrec.gov.in/pi-webpages/AmitDutt/IPD/IPD.html and for web-based processing at http://ipd.actrec.gov.in/ipdweb/ to generate an automated report without any prior computational know-how.


Subject(s)
Genome, Viral , Mutation Rate , SARS-CoV-2/genetics , Computational Biology , Humans
17.
Front Immunol ; 12: 658519, 2021.
Article in English | MEDLINE | ID: covidwho-1317222

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly pathogenic novel virus that has caused a massive pandemic called coronavirus disease 2019 (COVID-19) worldwide. Wuhan, a city in China became the epicenter of the outbreak of COVID-19 in December 2019. The disease was declared a pandemic globally by the World Health Organization (WHO) on 11 March 2020. SARS-CoV-2 is a beta CoV of the Coronaviridae family which usually causes respiratory symptoms that resemble common cold. Multiple countries have experienced multiple waves of the disease and scientific experts are consistently working to find answers to several unresolved questions, with the aim to find the most suitable ways to contain the virus. Furthermore, potential therapeutic strategies and vaccine development for COVID-19 management are also considered. Currently, substantial efforts have been made to develop successful and safe treatments and SARS-CoV-2 vaccines. Some vaccines, such as inactivated vaccines, nucleic acid-based, and vector-based vaccines, have entered phase 3 clinical trials. Additionally, diverse small molecule drugs, peptides and antibodies are being developed to treat COVID-19. We present here an overview of the virus interaction with the host and environment and anti-CoV therapeutic strategies; including vaccines and other methodologies, designed for prophylaxis and treatment of SARS-CoV-2 infection with the hope that this integrative analysis could help develop novel therapeutic approaches against COVID-19.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , Pandemics/prevention & control , SARS-CoV-2/immunology , Antibodies, Viral/immunology , Antibodies, Viral/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , COVID-19 Vaccines/immunology , Host Microbial Interactions/immunology , Humans , Immunity , Mutation Rate , SARS-CoV-2/genetics , Small Molecule Libraries/therapeutic use , Vaccines, DNA/immunology , Vaccines, DNA/therapeutic use , Vaccines, Inactivated/immunology , Vaccines, Inactivated/therapeutic use
18.
J Med Virol ; 93(12): 6479-6485, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1306658

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China in early December 2019 has rapidly widespread worldwide. Over the course of the pandemic, due to the advance of whole-genome sequencing technologies, an unprecedented number of genomes have been generated, providing both invaluable insights into the ongoing evolution and epidemiology of the virus and allowing the identification of hundreds of circulating genetic variants during the pandemic. In recent months variants of SARS-CoV-2 that have an increased number of mutations on the Spike protein have brought concern all over the world. These have been called "variants of concerns" (VOCs), and/or "variants of interests" (VOIs) as it has been suggested that their genome mutations might impact transmission, immune control, and virulence. Tracking the spread of emerging SARS-CoV-2 variants is crucial to inform public health efforts and control the ongoing pandemic. In this review, a concise characterization of the SARS-CoV-2 mutational patterns of the main VOCs and VOIs circulating and cocirculating worldwide has been presented to determine the magnitude of the SARS-CoV-2 threat to better understand the virus genetic diversity and its potential impact on vaccination strategy.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , COVID-19 Vaccines/immunology , China/epidemiology , Evolution, Molecular , Genome, Viral/genetics , Humans , Mutation , Mutation Rate , Phylogeny , Spike Glycoprotein, Coronavirus/immunology , Whole Genome Sequencing
19.
Virus Genes ; 57(5): 413-425, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1305168

ABSTRACT

Along with intrinsic evolution, adaptation to selective pressure in new environments might have resulted in the circulatory SARS-CoV-2 strains in response to the geoenvironmental conditions of a country and the demographic profile of its population. With this target, the current study traced the evolutionary route and mutational frequency of 198 Bangladesh-originated SARS-CoV-2 genomic sequences available in the GISAID platform over a period of 13 weeks as of 14 July 2020. The analyses were performed using MEGA X, Swiss Model Repository, Virus Pathogen Resource and Jalview visualization. Our analysis identified that majority of the circulating strains strikingly differ from both the reference genome and the first sequenced genome from Bangladesh. Mutations in nonspecific proteins (NSP2-3, NSP-12(RdRp), NSP-13(Helicase)), S-Spike, ORF3a, and N-Nucleocapsid protein were common in the circulating strains with varying degrees and the most unique mutations (UM) were found in NSP3 (UM-18). But no or limited changes were observed in NSP9, NSP11, Envelope protein (E) and accessory factors (NSP7a, ORF 6, ORF7b) suggesting the possible conserved functions of those proteins in SARS-CoV-2 propagation. However, along with D614G mutation, more than 20 different mutations in the Spike protein were detected basically in the S2 domain. Besides, mutations in SR-rich region of N protein and P323L in RDRP were also present. However, the mutation accumulation showed a significant association (p = 0.003) with sex and age of the COVID-19-positive cases. So, identification of these mutational accumulation patterns may greatly facilitate vaccine development deciphering the age and the sex-dependent differential susceptibility to COVID-19.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks , Genome, Viral/genetics , SARS-CoV-2/genetics , Age Factors , Bangladesh/epidemiology , COVID-19/virology , Female , Humans , Male , Mutation , Mutation Rate , Phylogeny , SARS-CoV-2/classification , Sex Factors , Spike Glycoprotein, Coronavirus/genetics , Viral Proteins/genetics
20.
J Med Virol ; 93(10): 6016-6026, 2021 10.
Article in English | MEDLINE | ID: covidwho-1303275

ABSTRACT

Novel mutations have been emerging in the genome of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2); consequently, the evolving of more virulent and treatment resistance strains have the potential to increase transmissibility and mortality rates. The characterization of full-length SARS-CoV-2 genomes is critical for understanding the origin and transmission pathways of the virus, as well as identifying mutations that affect the transmissibility and pathogenicity of the virus. We present an analysis of the mutation pattern and clade distribution of full-length SARS-CoV-2 genome sequences obtained from specimens tested at Gazi University Medical Virology Laboratory. Viral RNA was extracted from nasopharyngeal specimens. Next-generation sequencing libraries were prepared and sequenced on Illumina iSeq 100 platform. Raw sequencing data were processed to obtain full-length genome sequences and variant calling was performed to analyze amino acid changes. Clade distribution was determined to understand the phylogenetic background in relation to global data. A total of 293 distinct mutations were identified, of which 152 missense, 124 synonymous, 12 noncoding, and 5 deletions. The most frequent mutations were P323L (nsp12), D614G (ORF2/S), and 2421C>T (5'-untranslated region) found simultaneously in all sequences. Novel mutations were found in nsp12 (V111A, H133R, Y453C, M626K) and ORF2/S (R995G, V1068L). Nine different Pangolin lineages were detected. The most frequently assigned lineage was B.1.1 (17 sequences), followed by B.1 (7 sequences) and B.1.1.36 (3 sequences). Sequence information is essential for revealing genomic diversity. Mutations might have significant functional implications and analysis of these mutations provides valuable information for therapeutic and vaccine development studies. Our findings point to the introduction of the virus into Turkey through various sources and the subsequent spread of several key variants.


Subject(s)
COVID-19/virology , Coronavirus RNA-Dependent RNA Polymerase/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Adult , COVID-19/epidemiology , COVID-19/transmission , Female , Genome, Viral/genetics , Humans , Male , Mutation , Mutation Rate , Phylogeny , RNA, Viral/genetics , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Turkey/epidemiology
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