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1.
Emerg Infect Dis ; 30(6): 1289-1291, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38669127

RESUMO

Using the GISAID EpiCoV database, we identified 256 COVID-19 patients in Japan during March 31-December 31, 2023, who had mutations in the SARS-CoV-2 nonstructural protein 5 conferring ensitrelvir resistance. Ongoing genomic surveillance is required to monitor emergence of SARS-CoV-2 mutations that are resistant to anticoronaviral drugs.


Assuntos
Antivirais , COVID-19 , Farmacorresistência Viral , Mutação , SARS-CoV-2 , Humanos , Japão/epidemiologia , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/virologia , Farmacorresistência Viral/genética , Antivirais/uso terapêutico , Antivirais/farmacologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Proteínas não Estruturais Virais/genética , Tratamento Farmacológico da COVID-19 , Indazóis , Triazinas , Triazóis
2.
Microb Pathog ; 185: 106460, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37995880

RESUMO

The COVID-19 pandemic has been driven by the emergence of SARS-CoV-2 variants with mutations across all the viral proteins. Although mutations in the spike protein have received significant attention, understanding the prevalence and potential impact of mutations in other viral proteins is essential for comprehending the evolution of SARS-CoV-2. Here, we conducted a comprehensive analysis of approximately 14 million sequences of SARS-CoV-2 deposited in the GISAID database until December 2022 to identify prevalent mutations in the non-spike proteins at the global and country levels. Additionally, we evaluated the energetics of each mutation to better understand their impact on protein stability. While the consequences of many mutations remain unclear, we discuss potential structural and functional significance of some mutations. Our study highlights the ongoing evolutionary process of SARS-CoV-2 and underscores the importance of understanding changes in non-spike proteins.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Pandemias , Glicoproteína da Espícula de Coronavírus/genética , Mutação
3.
Med Microbiol Immunol ; 212(6): 437-446, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37789185

RESUMO

Several tools have been developed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genotyping based on either whole genome or spike sequencing. We aimed to highlight the molecular epidemiological landscape of SARS-CoV-2 in Egypt since the start of the pandemic, to describe discrepancies between the 3 typing tools: Global Initiative on Sharing Avian Influenza Data (GISAID), Nextclade, and Phylogenetic Assignment of Named Global Outbreak Lineages (PANGOLIN) and to assess the fitness of spike and nucleocapsid regions for lineage assignment compared to the whole genome. A total of 3935 sequences isolated from Egypt (March 2020-2023) were retrieved from the GISAID database. A subset of data (n = 1212) with high coverage whole genome was used for tool discrimination and agreement analyses. Among 1212 sequences, the highest discriminatory power was 0.895 for PANGOLIN, followed by GISAID (0.872) and Nextclade (0.866). There was a statistically significant difference (p = 0.0418) between lineages assigned via spike (30%) and nucleocapsid (46%) compared to their whole genome-assigned lineages. The first 3 pandemic waves were dominated by B.1, followed by C.36 and then C.36.3, while the fourth to sixth waves were dominated by the B.1.617.2, BA, and BA.5.2 lineages, respectively. Current shift in lineage typing to recombinant forms. The 3 typing tools showed comparable discrimination among SARS-CoV-2 lineages. The nucleocapsid region could be used for lineage assignment.


Assuntos
COVID-19 , Pangolins , Animais , Humanos , Egito/epidemiologia , Genótipo , Filogenia , SARS-CoV-2/genética , COVID-19/epidemiologia , Genômica , Nucleocapsídeo , Mutação
4.
Tohoku J Exp Med ; 260(1): 21-27, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-36792177

RESUMO

The genomes of sarbecoviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), incorporate mutations with short sequence exchanges based on unknown processes. Currently, the presence of such short-sequence exchanges among the genomes of different SARS-CoV-2 lineages remains uncertain. In the present study, multiple SARS-CoV-2 genome sequences from different clades or sublineages were collected from an international mass sequence database and compared to identify the presence of short sequence exchanges. Initial screening with multiple sequence alignments identified two locations with trinucleotide substitutions, both in the nucleocapsid (N) gene. The first exchange from 5'-GAT-3' to 5'-CTA-3' at nucleotide positions 28,280-28,282 resulted in a change in the amino acid from aspartic acid (D) to leucine (L), which was predominant in clade GRY (Alpha). The second exchange from 5'-GGG-3' to 5'-AAC-3' at nucleotide positions 28,881-28,883 resulted in an amino acid change from arginine and glycine (RG) to lysine and arginine (KR), which was predominant in GR (Gamma), GRY (Alpha), and GRA (Omicron). Both trinucleotide substitutions occurred before June 2020. The sequence identity rate between these lineages suggests that coincidental succession of single-nucleotide substitutions is unlikely. Basic local alignment search tool sequence search revealed the absence of intermediating mutations based on single-base substitutions or overlapping indels before the emergence of these trinucleotide substitutions. These findings suggest that trinucleotide substitutions could have developed via an en bloc exchange. In summary, trinucleotide substitutions at two locations in the SARS-CoV-2 N gene were identified. This mutation may provide insights into the evolution of SARS-CoV-2.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/genética , Mutação/genética , Nucleocapsídeo/genética , Nucleotídeos , Aminoácidos/genética , Filogenia
5.
Genomics ; 114(6): 110497, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36182010

RESUMO

The goal of this study was to identify the genomic variants and determine molecular epidemiology of SARS-CoV-2 virus during the early pandemic stage in Bangladesh. Viral RNA was extracted, converted to cDNA, and amplified using Ion AmpliSeq™ SARS-CoV-2 Research Panel. 413 unique mutants from 151 viral isolates were identified. 80% of cases belongs to 8 mutants: 241C toT, 1163A toT, 3037C toT, 14408C toT, 23403A toG, 28881G toA, 28,882 G toA, and 28883G toC. Observed dominance of GR clade variants that have strong presence in Europe, suggesting European channel a possible entry route. Among 37 genomic mutants significantly associated with clinical symptoms, 3916CtoT (associated with sore-throat), 14408C to T (associated with cough-protection), 28881G to A, 28882G to A, and 28883G to C (associated with chest pain) were notable. These findings may inform future research platforms for disease management and epidemiological study.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiologia , Genômica , China
6.
Environ Monit Assess ; 196(1): 44, 2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38102322

RESUMO

Wastewater surveillance locally and globally is important for the investigation of the molecular epidemiological features of SARS-CoV-2 in the environment. The current study investigated the genomic diversity and mutation profile of SARS-CoV-2 variants in wastewater for the period spanning COVID-19 pandemic up to December, 2022. A total of 3618 complete SARS-CoV-2 genome sequences from waste water samples submitted to the GISAID database were retrieved. The SARS-CoV-2 sequences were subjected to pairwise alignment against reference, followed by clade and lineage assignment (based on Nextstrain, GISAID and Pango), distance metric phylogenetic analysis, and detection of substitution mutations. Following GISAID, Nextstrain, and Pango nomenclatures, an overall agreement in clade and lineage determination in wastewater samples was observed. There was successive appearance, dissemination, and disappearance of SARS-CoV-2 lineages along time in wastewater. The SARS-CoV-2 genomes from wastewater were clustered into the variants of concern (VOC) as Alpha GRY (B.1.1.7 + Q.7), Delta GK (B.1.617.2 + AY.*), and Omicron GRA (BA.1*, BA.2* + B.1.1.529, BA.5*). The evolutionary rate was 9.63e-04 substitutions/site/year for SARS-CoV-2 in wastewater. B.1.1.7 was less prevalent than B.1.617.2 in 2021, appeared in succession, and BA.1, BA.2, BA.5 were serially detected in 2022, the latter strain continued to persist in wastewater. The N501Y, E484K/Q, K417N/T, L452R, T478K spike substitutions remained dominant attribute of SARS-CoV-2 VOCs. The study underlines the importance of wastewater surveillance for enumerating spatiotemporal diversity of SARS-CoV-2 variants and mutations, which might pave the way for novel antiviral and vaccine designing towards management and prevention of SARS-CoV-2 infection.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Águas Residuárias , COVID-19/epidemiologia , Pandemias , Filogenia , Vigilância Epidemiológica Baseada em Águas Residuárias , Monitoramento Ambiental , Estudos Epidemiológicos , Mutação
7.
Genet Epidemiol ; 45(7): 685-693, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34159627

RESUMO

SARS-CoV-2 mortality has been extensively studied in relation to host susceptibility. How sequence variations in the SARS-CoV-2 genome affect pathogenicity is poorly understood. Starting in October 2020, using the methodology of genome-wide association studies (GWAS), we looked at the association between whole-genome sequencing (WGS) data of the virus and COVID-19 mortality as a potential method of early identification of highly pathogenic strains to target for containment. Although continuously updating our analysis, in December 2020, we analyzed 7548 single-stranded SARS-CoV-2 genomes of COVID-19 patients in the GISAID database and associated variants with mortality using a logistic regression. In total, evaluating 29,891 sequenced loci of the viral genome for association with patient/host mortality, two loci, at 12,053 and 25,088 bp, achieved genome-wide significance (p values of 4.09e-09 and 4.41e-23, respectively), though only 25,088 bp remained significant in follow-up analyses. Our association findings were exclusively driven by the samples that were submitted from Brazil (p value of 4.90e-13 for 25,088 bp). The mutation frequency of 25,088 bp in the Brazilian samples on GISAID has rapidly increased from about 0.4 in October/December 2020 to 0.77 in March 2021. Although GWAS methodology is suitable for samples in which mutation frequencies varies between geographical regions, it cannot account for mutation frequencies that change rapidly overtime, rendering a GWAS follow-up analysis of the GISAID samples that have been submitted after December 2020 as invalid. The locus at 25,088 bp is located in the P.1 strain, which later (April 2021) became one of the distinguishing loci (precisely, substitution V1176F) of the Brazilian strain as defined by the Centers for Disease Control. Specifically, the mutations at 25,088 bp occur in the S2 subunit of the SARS-CoV-2 spike protein, which plays a key role in viral entry of target host cells. Since the mutations alter amino acid coding sequences, they potentially imposing structural changes that could enhance viral infectivity and symptom severity. Our analysis suggests that GWAS methodology can provide suitable analysis tools for the real-time detection of new more transmissible and pathogenic viral strains in databases such as GISAID, though new approaches are needed to accommodate rapidly changing mutation frequencies over time, in the presence of simultaneously changing case/control ratios. Improvements of the associated metadata/patient information in terms of quality and availability will also be important to fully utilize the potential of GWAS methodology in this field.


Assuntos
COVID-19 , Glicoproteína da Espícula de Coronavírus , Brasil , Estudo de Associação Genômica Ampla , Humanos , Mutação , Filogenia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética
8.
Microchem J ; 167: 106305, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33897053

RESUMO

Since December 2019, we have been in the battlefield with a new threat to the humanity known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we describe the four main methods used for diagnosis, screening and/or surveillance of SARS-CoV-2: Real-time reverse transcription polymerase chain reaction (RT-PCR); chest computed tomography (CT); and different complementary alternatives developed in order to obtain rapid results, antigen and antibody detection. All of them compare the highlighting advantages and disadvantages from an analytical point of view. The gold standard method in terms of sensitivity and specificity is the RT-PCR. The different modifications propose to make it more rapid and applicable at point of care (POC) are also presented and discussed. CT images are limited to central hospitals. However, being combined with RT-PCR is the most robust and accurate way to confirm COVID-19 infection. Antibody tests, although unable to provide reliable results on the status of the infection, are suitable for carrying out maximum screening of the population in order to know the immune capacity. More recently, antigen tests, less sensitive than RT-PCR, have been authorized to determine in a quicker way whether the patient is infected at the time of analysis and without the need of specific instruments.

9.
Mol Cell Probes ; 53: 101599, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32425334

RESUMO

•Most of the COVID-19 cases in Nepal are in the Southern districts of Nepal bordering India with travel histories to India.•Very few positive cases of COVID-19 are detected in Nepal which could either be due to early national lockdown.•Low PCR positivity rates could also be due to inefficiency of the PCR methods.•Whole genomes of 93 clinical samples from COVID-19 patients were analyzed to find the primer and probe binding sites.•Mutations in probe binding sites were found which could impact PCR efficiency resulting in false negative results.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Genoma Viral , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Betacoronavirus/classificação , Betacoronavirus/patogenicidade , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Sondas de DNA/normas , Reações Falso-Negativas , Humanos , Índia/epidemiologia , Mutação , Nepal/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Kit de Reagentes para Diagnóstico/normas , SARS-CoV-2 , Índice de Gravidade de Doença , Migrantes
10.
EBioMedicine ; 91: 104534, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37004335

RESUMO

BACKGROUND: Throughout the COVID-19 pandemic, the SARS-CoV-2 virus has continued to evolve, with new variants outcompeting existing variants and often leading to different dynamics of disease spread. METHODS: In this paper, we performed a retrospective analysis using longitudinal sequencing data to characterize differences in the speed, calendar timing, and magnitude of 16 SARS-CoV-2 variant waves/transitions for 230 countries and sub-country regions, between October 2020 and January 2023. We then clustered geographic locations in terms of their variant behavior across several Omicron variants, allowing us to identify groups of locations exhibiting similar variant transitions. Finally, we explored relationships between heterogeneity in these variant waves and time-varying factors, including vaccination status of the population, governmental policy, and the number of variants in simultaneous competition. FINDINGS: This work demonstrates associations between the behavior of an emerging variant and the number of co-circulating variants as well as the demographic context of the population. We also observed an association between high vaccination rates and variant transition dynamics prior to the Mu and Delta variant transitions. INTERPRETATION: These results suggest the behavior of an emergent variant may be sensitive to the immunologic and demographic context of its location. Additionally, this work represents the most comprehensive characterization of variant transitions globally to date. FUNDING: Laboratory Directed Research and Development (LDRD), Los Alamos National Laboratory.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias , Estudos Retrospectivos
11.
Genes (Basel) ; 14(1)2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36672914

RESUMO

Omicron variants have been classified as Variants of Concern (VOC) by the World Health Organization (WHO) ever since they first emerged as a result of a significant mutation in this variant, which showed to have an impact on transmissibility and virulence of the virus, as evidenced by the ongoing modifications in the SARS-CoV-2 virus. As a global pandemic, the Omicron variant also spread among the Kurdish population. This study aimed to analyze different strains from different cities of the Kurdistan region of Iraq to show the risk of infection and the impact of the various mutations on immune responses and vaccination. A total of 175 nasopharyngeal/oropharyngeal specimens were collected at West Erbil Emergency Hospital and confirmed for SARS-CoV-2 infection by RT-PCR. The genomes of the samples were sequenced using the Illumina COVID-Seq Method. The genome analysis was established based on previously published data in the GISAID database and compared to previously detected mutations in the Omicron variants, and that they belong to the BA.1 lineage and include most variations determined in other studies related to transmissibility, high infectivity and immune escape. Most of the mutations were found in the RBD (receptor binding domain), the region related to the escape from humoral immunity. Remarkably, these point mutations (G339D, S371L, S373P, S375F, T547K, D614G, H655Y, N679K and N969K) were also determined in this study, which were unique, and their impact should be addressed more. Overall, the Omicron variants were more contagious than other variants. However, the mortality rate was low, and most infectious cases were asymptomatic. The next step should address the potential of Omicron variants to develop the next-generation COVID-19 vaccine.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Filogenia , Iraque/epidemiologia , Vacinas contra COVID-19 , COVID-19/epidemiologia , COVID-19/genética , Genômica
12.
J Infect Public Health ; 16(10): 1544-1555, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37566991

RESUMO

BACKGROUND: The SARS-CoV-2 pandemic, caused by the novel coronavirus, has posed a significant global health threat since its emergence in late 2019. The World Health Organization declared the outbreak a pandemic on March 11, 2020, due to its rapid global spread and impact on public health. New variants have raised concerns about their potential impact on the transmission of the virus and the effectiveness of current diagnostic tools, treatments, and vaccines. This study aims to investigate the effect of new variants in Pakistani virus strains on human receptors, specifically ACE2 and NRP1. In-silico analysis provides a powerful tool to analyze the potential impact of new variants on protein structure, function, and interactions. OBJECTIVES: The SARS-CoV-2 virus is evolving quickly. After being exposed in Wuhan, SARS-CoV-2 underwent numerous mutations, leading to several variants' emergence. These variants stabilize the interaction of spike protein with human receptors ACE2 and NRP1. The study aims to check the molecular effect of these variants on human receptors using the in-silico approach. MATERIAL AND METHODS: We use in-silico mutational tools to analyze new variants in SARS-CoV-2 and to check the molecular interaction of spike protein with human receptors (ACE2 and NRP1). Genomic sequences of 41 SARS-CoV-2 strains were sequenced using Ion Torrent (NGS) and submitted to the GISAID database. Spike protein of SARS-CoV-2 sequence trimmed and translated into a protein sequence using ExPasy. We used multiple sequence alignments to check for variants in the spike protein of strains. We utilized mutation tools such as Mupro, SIFT, SNAP2, and Mutpred2.3D structures of SARS-CoV-2 spike proteins (wild and mutated) to analyze further the mutations, ACE2 and NRP1 modelled by the ITASSER protein modelling server. Interactions of spike proteins (wild and mutant) analyzed by MD Docking, Simulation, and MMGBSA RESULTS: Variants I210T, V213G, S371F, S373P, T478K, F486V, Y505H, and D796Y were identified in SARS-CoV-2 Pakistani strains' spike protein. Variant Y505H were found to affect protein function. MD Docking, MMGBSA and MD simulation revealed that these variants increased spike protein's binding affinity with human receptors (ACE2 and NRP1). MD simulation revealed that mutated spike protein stabilized earlier than wild when interacting with ACE2 after 40 ns and interaction with NRP1 stabilized after 30 ns for mutated spike protein compared to wild. CONCLUSION: These variants in Pakistani strains of SARS-CoV-2 are increasing the stability of spike protein with human receptors. These findings provide insight into how the SARS-CoV-2 virus evolves and adapts to human hosts. This information may help develop strategies to control the virus's spread and develop effective treatments and vaccines in the future.


Assuntos
COVID-19 , Simulação de Dinâmica Molecular , Humanos , RNA Viral , Glicoproteína da Espícula de Coronavírus/genética , Enzima de Conversão de Angiotensina 2 , SARS-CoV-2/genética , Ligação Proteica , Mutação
13.
Viruses ; 15(5)2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37243134

RESUMO

Drug appropriateness is a pillar of modern evidence-based medicine, but the turnaround times of genomic sequencing are not compatible with the urgent need to deliver treatments against microorganisms. Massive worldwide genomic surveillance has created an unprecedented landscape for exploiting viral sequencing for therapeutic purposes. When it comes to therapeutic antiviral antibodies, using IC50 against specific polymorphisms of the target antigen can be calculated in vitro, and a list of mutations leading to drug resistance (immune escape) can be compiled. The author encountered this type of knowledge (available from the Stanford University Coronavirus Antiviral Resistance Database,) in a publicly accessible repository of SARS-CoV-2 sequences. The author used a custom function of the CoV-Spectrum.org web portal to deliver up-to-date, regional prevalence estimates of baseline efficacy for each authorized anti-spike mAb across all co-circulating SARS-CoV-2 sublineages at a given time point. This publicly accessible tool can inform therapeutic choices that would otherwise be blind.


Assuntos
COVID-19 , Humanos , SARS-CoV-2/genética , Genômica , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Antivirais , Glicoproteína da Espícula de Coronavírus/genética , Anticorpos Neutralizantes
14.
Vaccines (Basel) ; 11(4)2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37112648

RESUMO

Coronaviruses belong to the group of RNA family of viruses that trigger diseases in birds, humans, and mammals, which can cause respiratory tract infections. The COVID-19 pandemic has badly affected every part of the world. Our study aimed to explore the genome of SARS-CoV-2, followed by in silico analysis of its proteins. Different nucleotide and protein variants of SARS-CoV-2 were retrieved from NCBI. Contigs and consensus sequences were developed to identify these variants using SnapGene. Data of the variants that significantly differed from each other was run through Predict Protein software to understand the changes produced in the protein structure. The SOPMA web server was used to predict the secondary structure of the proteins. Tertiary structure details of the selected proteins were analyzed using the web server SWISS-MODEL. Sequencing results showed numerous single nucleotide polymorphisms in the surface glycoprotein, nucleocapsid, ORF1a, and ORF1ab polyprotein while the envelope, membrane, ORF3a, ORF6, ORF7a, ORF8, and ORF10 genes had no or few SNPs. Contigs were used to identify variations in the Alpha and Delta variants of SARS-CoV-2 with the reference strain (Wuhan). Some of the secondary structures of the SARS-CoV-2 proteins were predicted by using Sopma software and were further compared with reference strains of SARS-CoV-2 (Wuhan) proteins. The tertiary structure details of only spike proteins were analyzed through the SWISS-MODEL and Ramachandran plots. Through the Swiss-model, a comparison of the tertiary structure model of the SARS-CoV-2 spike protein of the Alpha and Delta variants was made with the reference strain (Wuhan). Alpha and Delta variants of the SARS-CoV-2 isolates submitted in GISAID from Pakistan with changes in structural and nonstructural proteins were compared with the reference strain, and 3D structure mapping of the spike glycoprotein and mutations in the amino acids were seen. The surprisingly increased rate of SARS-CoV-2 transmission has forced numerous countries to impose a total lockdown due to an unusual occurrence. In this research, we employed in silico computational tools to analyze the SARS-CoV-2 genomes worldwide to detect vital variations in structural proteins and dynamic changes in all SARS-CoV-2 proteins, mainly spike proteins, produced due to many mutations. Our analysis revealed substantial differences in the functionality, immunological, physicochemical, and structural variations in the SARS-CoV-2 isolates. However, the real impact of these SNPs can only be determined further by experiments. Our results can aid in vivo and in vitro experiments in the future.

16.
PNAS Nexus ; 1(4): pgac197, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36714870

RESUMO

Mutations in nonstructural protein 3 (nsp3) and nsp4 of SARS-CoV-2, presumably induced by the asthma drug ciclesonide (which also has anti-SARS-CoV-2 activity), were counted 5,851 cases in the GISAID EpiCoV genome database. Sporadic occurrence of mutants not linked to each other in the phylogenetic tree were identified at least 88 times; of which, 58 had one or more descendants in the same branch. Five of these had spread to more than 100 cases, and one had expanded to 4,748 cases, suggesting the mutations are frequent, selected in individual patients, and transmitted to form clusters of cases. Clinical trials of ciclesonide as a treatment for COVID-19 are the presumed cause of the frequent occurrence of mutations between 2020 June and 2021 November. In addition, because ciclesonide is a common treatment for asthma, it can drive mutations in asthmatics suffering from COVID-19. Ciclesonide-resistant mutations, which have unpredictable effects in humans, are likely to continue to emerge because SARS-CoV-2 remains prevalent globally.

17.
Virus Res ; 317: 198824, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35605880

RESUMO

The COVID-19 pandemic continues to pose a global health concern, despite the ongoing vaccination campaigns, due to the emergence and rapid spread of new variants of the causative agent SARS-CoV-2. These variants are identified and tracked via the marker mutations they carry, and the classification system put in place following tremendous sequencing efforts. In this study, the genomes of 1,230 Lebanese SARS-CoV-2 strains collected throughout 2 years of the outbreak in Lebanon were analyzed, 115 of which sequenced within this project. Strains were classified into seven GISAID clades, the major one being GRY, and 36 Pango lineages, with three variants of concern identified: alpha, delta and omicron. A time course distribution of GISAID clades allowed the visualization of change throughout the two years of the Lebanese outbreak, in conjunction with major events and measures in the country. Subsequent phylogenetic analysis showed the clustering of strains belonging to the same clades. In addition, a mutational survey showed the presence of mutations in the structural, non-structural and accessory proteins. Twenty five (25) mutations were labeled as major, i.e. present in more than 30% of the strains, such as the common Spike_D614G and NSP3_T183I. Whereas 635 were labeled as uncommon, i.e. found in very few of the analyzed strains as well as GISAID records, such as NSP2_I349V. Distribution of these mutations differed between 2020, and the first and the second half of 2021. In summary, this study highlights key genomic aspects of the Lebanese SARS-CoV-2 strains collected in 2020, the first year of the outbreak in Lebanon, versus those collected in 2021, the second year of COVID-19 in Lebanon.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Genômica , Humanos , Mutação , Pandemias , Filogenia , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
18.
Front Genet ; 13: 801332, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154274

RESUMO

Early detection of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) variants and use of data for public health action requires a coordinated, rapid, and high throughput approach to whole genome sequencing (WGS). Currently, WGS output from many low- and middle-income countries (LMIC) has lagged. By fostering diverse partnerships and multiple sequencing technologies, Indonesia accelerated SARS-CoV-2 WGS uploads to GISAID from 1,210 in April 2021 to 5,791 in August 2021, an increase from 11 submissions per day between January to May, to 43 per day between June to August. Turn-around-time from specimen collection to submission decreased from 77 to 5 days, allowing for timely public health decisions. These changes were enabled by establishment of the National Genomic Surveillance Consortium, coordination between public and private sector laboratories with WGS capability, and diversification of sequencing platform technologies. Here we present how diversification on multiple levels enabled a rapid and significant increase of national WGS performance, with potentially valuable lessons for other LMICs.

19.
Microorganisms ; 10(7)2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35889075

RESUMO

Here, we report the emergence of the variant lineage B.1.1.523 that contains a set of mutations including 156_158del, E484K and S494P in the spike protein. E484K and S494P are known to significantly reduce SARS-CoV-2 neutralization by convalescent and vaccinated sera and are considered as mutations of concern. Lineage B.1.1.523 presumably originated in the Russian Federation and spread across European countries with the peak of transmission in April-May 2021. The B.1.1.523 lineage has now been reported from 31 countries. In this article, we analyze the possible origin of this mutation subset and its immune response using in silico methods.

20.
Viruses ; 14(4)2022 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-35458508

RESUMO

Whole-genome sequencing (WGS) has played a significant role in understanding the epidemiology and biology of SARS-CoV-2 virus. Here, we investigate the use of SARS-CoV-2 WGS in Southeast and East Asian countries as a genomic surveillance during the COVID-19 pandemic. Nottingham-Indonesia Collaboration for Clinical Research and Training (NICCRAT) initiative has facilitated collaboration between the University of Nottingham and a team in the Research Center for Biotechnology, National Research and Innovation Agency (BRIN), to carry out a small number of SARS-CoV-2 WGS in Indonesia using Oxford Nanopore Technology (ONT). Analyses of SARS- CoV-2 genomes deposited on GISAID reveal the importance of clinical and demographic metadata collection and the importance of open access and data sharing. Lineage and phylogenetic analyses of two periods defined by the Delta variant outbreak reveal that: (1) B.1.466.2 variants were the most predominant in Indonesia before the Delta variant outbreak, having a unique spike gene mutation N439K at more than 98% frequency, (2) Delta variants AY.23 sub-lineage took over after June 2021, and (3) the highest rate of virus transmissions between Indonesia and other countries was through interactions with Singapore and Japan, two neighbouring countries with a high degree of access and travels to and from Indonesia.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Humanos , Indonésia/epidemiologia , Mutação , Pandemias , Filogenia , SARS-CoV-2/genética
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