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1.
Viruses ; 13(2)2021 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-33557213

RESUMEN

Monitoring acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic diversity and emerging mutations in this ongoing pandemic is crucial for understanding its evolution and assuring the performance of diagnostic tests, vaccines, and therapies against coronavirus disease (COVID-19). This study reports on the amino acid (aa) conservation degree and the global and regional temporal evolution by epidemiological week for each residue of the following four structural SARS-CoV-2 proteins: spike, envelope, membrane, and nucleocapsid. All, 105,276 worldwide SARS-CoV-2 complete and partial sequences from 117 countries available in the Global Initiative on Sharing All Influenza Data (GISAID) from 29 December 2019 to 12 September 2020 were downloaded and processed using an in-house bioinformatics tool. Despite the extremely high conservation of SARS-CoV-2 structural proteins (>99%), all presented aa changes, i.e., 142 aa changes in 65 of the 75 envelope aa, 291 aa changes in 165 of the 222 membrane aa, 890 aa changes in 359 of the 419 nucleocapsid aa, and 2671 changes in 1132 of the 1273 spike aa. Mutations evolution differed across geographic regions and epidemiological weeks (epiweeks). The most prevalent aa changes were D614G (81.5%) in the spike protein, followed by the R203K and G204R combination (37%) in the nucleocapsid protein. The presented data provide insight into the genetic variability of SARS-CoV-2 structural proteins during the pandemic and highlights local and worldwide emerging aa changes of interest for further SARS-CoV-2 structural and functional analysis.


Asunto(s)
/virología , /genética , Evolución Molecular , Glicoproteína de la Espiga del Coronavirus/genética , Proteínas de la Matriz Viral/genética , Sustitución de Aminoácidos , /química , Variación Genética , Genoma Viral , Humanos , Mutación , Pandemias , Fosfoproteínas/química , Fosfoproteínas/genética , Glicoproteína de la Espiga del Coronavirus/química , Proteínas de la Matriz Viral/química
2.
BMC Bioinformatics ; 22(1): 45, 2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33541262

RESUMEN

BACKGROUND: Several bioinformatics pipelines have been developed to detect sequences from viruses that integrate into the human genome because of the health relevance of these integrations, such as in the persistence of viral infection and/or in generating genotoxic effects, often progressing into cancer. Recent genomics and metagenomics analyses have shown that viruses also integrate into the genome of non-model organisms (i.e., arthropods, fish, plants, vertebrates). However, rarely studies of endogenous viral elements (EVEs) in non-model organisms have gone beyond their characterization from reference genome assemblies. In non-model organisms, we lack a thorough understanding of the widespread occurrence of EVEs and their biological relevance, apart from sporadic cases which nevertheless point to significant roles of EVEs in immunity and regulation of expression. The concomitance of repetitive DNA, duplications and/or assembly fragmentations in a genome sequence and intrasample variability in whole-genome sequencing (WGS) data could determine misalignments when mapping data to a genome assembly. This phenomenon hinders our ability to properly identify integration sites. RESULTS: To fill this gap, we developed ViR, a pipeline which solves the dispersion of reads due to intrasample variability in sequencing data from both single and pooled DNA samples thus ameliorating the detection of integration sites. We tested ViR to work with both in silico and real sequencing data from a non-model organism, the arboviral vector Aedes albopictus. Potential viral integrations predicted by ViR were molecularly validated supporting the accuracy of ViR results. CONCLUSION: ViR will open new venues to explore the biology of EVEs, especially in non-model organisms. Importantly, while we generated ViR with the identification of EVEs in mind, its application can be extended to detect any lateral transfer event providing an ad-hoc sequence to interrogate.


Asunto(s)
Mosquitos Vectores , Integración Viral , Secuenciación Completa del Genoma , Animales , Biología Computacional , Genoma Viral , Genómica , Humanos , Integración Viral/genética
3.
Int J Mol Sci ; 22(3)2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33525651

RESUMEN

Since early 2020, the COVID-19 pandemic has caused an excess in morbidity and mortality rates worldwide. Containment strategies rely firstly on rapid and sensitive laboratory diagnosis, with molecular detection of the viral genome in respiratory samples being the gold standard. The reliability of diagnostic protocols could be affected by SARS-CoV-2 genetic variability. In fact, mutations occurring during SARS-CoV-2 genomic evolution can involve the regions targeted by the diagnostic probes. Following a review of the literature and an in silico analysis of the most recently described virus variants (including the UK B 1.1.7 and the South Africa 501Y.V2 variants), we conclude that the described genetic variability should have minimal or no effect on the sensitivity of existing diagnostic protocols for SARS-CoV-2 genome detection. However, given the continuous emergence of new variants, the situation should be monitored in the future, and protocols including multiple targets should be preferred.


Asunto(s)
/métodos , /aislamiento & purificación , /virología , Genoma Viral , Humanos , Mutación , /genética
4.
Int J Mol Sci ; 22(3)2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33525632

RESUMEN

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel epidemic strain of Betacoronavirus that is responsible for the current viral pandemic, coronavirus disease 2019 (COVID-19), a global health crisis. Other epidemic Betacoronaviruses include the 2003 SARS-CoV-1 and the 2009 Middle East Respiratory Syndrome Coronavirus (MERS-CoV), the genomes of which, particularly that of SARS-CoV-1, are similar to that of the 2019 SARS-CoV-2. In this extensive review, we document the most recent information on Coronavirus proteins, with emphasis on the membrane proteins in the Coronaviridae family. We include information on their structures, functions, and participation in pathogenesis. While the shared proteins among the different coronaviruses may vary in structure and function, they all seem to be multifunctional, a common theme interconnecting these viruses. Many transmembrane proteins encoded within the SARS-CoV-2 genome play important roles in the infection cycle while others have functions yet to be understood. We compare the various structural and nonstructural proteins within the Coronaviridae family to elucidate potential overlaps and parallels in function, focusing primarily on the transmembrane proteins and their influences on host membrane arrangements, secretory pathways, cellular growth inhibition, cell death and immune responses during the viral replication cycle. We also offer bioinformatic analyses of potential viroporin activities of the membrane proteins and their sequence similarities to the Envelope (E) protein. In the last major part of the review, we discuss complement, stimulation of inflammation, and immune evasion/suppression that leads to CoV-derived severe disease and mortality. The overall pathogenesis and disease progression of CoVs is put into perspective by indicating several stages in the resulting infection process in which both host and antiviral therapies could be targeted to block the viral cycle. Lastly, we discuss the development of adaptive immunity against various structural proteins, indicating specific vulnerable regions in the proteins. We discuss current CoV vaccine development approaches with purified proteins, attenuated viruses and DNA vaccines.


Asunto(s)
Betacoronavirus/fisiología , Infecciones por Coronavirus/metabolismo , Proteínas de la Matriz Viral/metabolismo , Animales , Betacoronavirus/genética , Betacoronavirus/inmunología , /metabolismo , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Genoma Viral , Interacciones Huésped-Patógeno , Humanos , Evasión Inmune , Mapas de Interacción de Proteínas , /inmunología , Proteínas de la Matriz Viral/genética , Proteínas de la Matriz Viral/inmunología , Internalización del Virus , Replicación Viral
6.
Cells ; 10(2)2021 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-33557205

RESUMEN

Our knowledge of the evolution and the role of untranslated region (UTR) in SARS-CoV-2 pathogenicity is very limited. Leader sequence, originated from UTR, is found at the 5' ends of all encoded SARS-CoV-2 transcripts, highlighting its importance. Here, evolution of leader sequence was compared between human pathogenic and non-pathogenic coronaviruses. Then, profiling of microRNAs that can inactivate the key UTR regions of coronaviruses was carried out. A distinguished pattern of evolution in leader sequence of SARS-CoV-2 was found. Mining all available microRNA families against leader sequences of coronaviruses resulted in discovery of 39 microRNAs with a stable thermodynamic binding energy. Notably, SARS-CoV-2 had a lower binding stability against microRNAs. hsa-MIR-5004-3p was the only human microRNA able to target the leader sequence of SARS and to a lesser extent, also SARS-CoV-2. However, its binding stability decreased remarkably in SARS-COV-2. We found some plant microRNAs with low and stable binding energy against SARS-COV-2. Meta-analysis documented a significant (p < 0.01) decline in the expression of MIR-5004-3p after SARS-COV-2 infection in trachea, lung biopsy, and bronchial organoids as well as lung-derived Calu-3 and A549 cells. The paucity of the innate human inhibitory microRNAs to bind to leader sequence of SARS-CoV-2 can contribute to its high replication in infected human cells.


Asunto(s)
Regiones no Traducidas 5' , MicroARNs/genética , Replicación Viral , Animales , Biología Computacional , Evolución Molecular , Genoma Viral , Humanos , MicroARNs/farmacología , Conformación de Ácido Nucleico , ARN de Planta/farmacología , /fisiología
7.
Epidemiol Infect ; 149: e38, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33517929

RESUMEN

One of the main concerns about the fast spreading coronavirus disease 2019 (Covid-19) pandemic is how to intervene. We analysed severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) isolates data using the multifractal approach and found a rich in viral genome diversity, which could be one of the root causes of the fast Covid-19 pandemic and is strongly affected by pressure and health index of the hosts inhabited regions. The calculated mutation rate (mr) is observed to be maximum at a particular pressure, beyond which mr maintains diversity. Hurst exponent and fractal dimension are found to be optimal at a critical pressure (Pm), whereas, for P > Pm and P < Pm, we found rich genome diversity relating to complicated genome organisation and virulence of the virus. The values of these complexity measurement parameters are found to be increased linearly with health index values.


Asunto(s)
/virología , Tasa de Mutación , /genética , Genoma Viral/genética , Humanos
8.
J Vet Sci ; 22(1): e12, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33522164

RESUMEN

BACKGROUND: Bats have been considered natural reservoirs for several pathogenic human coronaviruses (CoVs) in the last two decades. Recently, a bat CoV was detected in the Republic of Korea; its entire genome was sequenced and reported to be genetically similar to that of the severe acute respiratory syndrome CoV (SARS-CoV). OBJECTIVES: The objective of this study was to compare the genetic sequences of SARS-CoV, SARS-CoV-2, and the two Korean bat CoV strains 16BO133 and B15-21, to estimate the likelihood of an interaction between the Korean bat CoVs and the human angiotensin-converting enzyme 2 (ACE2) receptor. METHODS: The phylogenetic analysis was conducted with the maximum-likelihood (ML) method using MEGA 7 software. The Korean bat CoVs receptor binding domain (RBD) of the spike protein was analyzed by comparative homology modeling using the SWISS-MODEL server. The binding energies of the complexes were calculated using PRODIGY and MM/GBGA. RESULTS: Phylogenetic analyses of the entire RNA-dependent RNA polymerase, spike regions, and the complete genome revealed that the Korean CoVs, along with SARS-CoV and SARS-CoV-2, belong to the subgenus Sarbecovirus, within BetaCoVs. However, the two Korean CoVs were distinct from SARS-CoV-2. Specifically, the spike gene of the Korean CoVs, which is involved in host infection, differed from that of SARS-CoV-2, showing only 66.8%-67.0% nucleotide homology and presented deletions within the RBD, particularly within regions critical for cross-species transmission and that mediate interaction with ACE2. Binding free energy calculation revealed that the binding affinity of Korean bat CoV RBD to hACE2 was drastically lower than that of SARS-CoV and SARS-CoV-2. CONCLUSIONS: These results suggest that Korean bat CoVs are unlikely to bind to the human ACE2 receptor.


Asunto(s)
Quirópteros/virología , Coronavirus/genética , Virus del SRAS/genética , /genética , Animales , Genes Virales/genética , Genoma Viral/genética , Genómica , Humanos , Funciones de Verosimilitud , Filogenia , Receptor de Angiotensina Tipo 2/genética , Receptor de Angiotensina Tipo 2/metabolismo , República de Corea , Análisis de Secuencia de ADN , Homología de Secuencia , Glicoproteína de la Espiga del Coronavirus/genética , Acoplamiento Viral
9.
Genome Med ; 13(1): 21, 2021 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-33563320

RESUMEN

We present CoronaHiT, a platform and throughput flexible method for sequencing SARS-CoV-2 genomes (≤ 96 on MinION or > 96 on Illumina NextSeq) depending on changing requirements experienced during the pandemic. CoronaHiT uses transposase-based library preparation of ARTIC PCR products. Method performance was demonstrated by sequencing 2 plates containing 95 and 59 SARS-CoV-2 genomes on nanopore and Illumina platforms and comparing to the ARTIC LoCost nanopore method. Of the 154 samples sequenced using all 3 methods, ≥ 90% genome coverage was obtained for 64.3% using ARTIC LoCost, 71.4% using CoronaHiT-ONT and 76.6% using CoronaHiT-Illumina, with almost identical clustering on a maximum likelihood tree. This protocol will aid the rapid expansion of SARS-CoV-2 genome sequencing globally.


Asunto(s)
/genética , Genoma Viral/genética , Pandemias , /genética , /virología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , ARN Viral/genética , Secuenciación Completa del Genoma
10.
PLoS One ; 16(2): e0246173, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33529260

RESUMEN

We report clinical profile of hundred and nine patients with SARS CoV-2 infection, and whole genome sequences (WGS) of seven virus isolates from the first reported cases in India, with various international travel histories. Comorbidities such as diabetes, hypertension, and cardiovascular disease were frequently associated with severity of the disease. WBC and neutrophil counts showed an increase, while lymphocyte counts decreased in patients with severe infection suggesting a possible neutrophil mediated organ damage, while immune activity may be diminished with decrease in lymphocytes leading to disease severity. Increase in SGOT, SGPT and blood urea suggests the functional deficiencies of liver, heart, and kidney in patients who succumbed to the disease when compared to the group of recovered patients. The WGS analysis showed that these isolates were classified into two clades: I/A3i, and A2a (four according to GISAID: O, L, GR, and GH). Further, WGS phylogeny and travel history together indicate possible transmission from Middle East and Europe. Three S protein variants: Wuhan reference, D614G, and Y28H were identified predicted to possess different binding affinities to host ACE2.


Asunto(s)
/virología , Genoma Viral , Secuenciación Completa del Genoma , Adulto , Anciano , /metabolismo , /patología , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Filogenia , ARN Viral/genética , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo
11.
Nat Commun ; 12(1): 1044, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33594055

RESUMEN

CrAssphage is the most abundant human-associated virus and the founding member of a large group of bacteriophages, discovered in animal-associated and environmental metagenomes, that infect bacteria of the phylum Bacteroidetes. We analyze 4907 Circular Metagenome Assembled Genomes (cMAGs) of putative viruses from human gut microbiomes and identify nearly 600 genomes of crAss-like phages that account for nearly 87% of the DNA reads mapped to these cMAGs. Phylogenetic analysis of conserved genes demonstrates the monophyly of crAss-like phages, a putative virus order, and of 5 branches, potential families within that order, two of which have not been identified previously. The phage genomes in one of these families are almost twofold larger than the crAssphage genome (145-192 kilobases), with high density of self-splicing introns and inteins. Many crAss-like phages encode suppressor tRNAs that enable read-through of UGA or UAG stop-codons, mostly, in late phage genes. A distinct feature of the crAss-like phages is the recurrent switch of the phage DNA polymerase type between A and B families. Thus, comparative genomic analysis of the expanded assemblage of crAss-like phages reveals aspects of genome architecture and expression as well as phage biology that were not apparent from the previous work on phage genomics.


Asunto(s)
Bacteriófagos/genética , Microbioma Gastrointestinal/genética , Genoma Viral , Metagenoma , Codón/genética , Secuencia Conservada , ADN Polimerasa Dirigida por ADN/metabolismo , Humanos , Inteínas , Intrones/genética , Sistemas de Lectura Abierta/genética , Filogenia , Empalme del ARN/genética , Transcripción Genética , /genética
12.
Sci Rep ; 11(1): 3934, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33594223

RESUMEN

Accumulating evidence supports the high prevalence of co-infections among Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) patients, and their potential to worsen the clinical outcome of COVID-19. However, there are few data on Southern Hemisphere populations, and most studies to date have investigated a narrow spectrum of viruses using targeted qRT-PCR. Here we assessed respiratory viral co-infections among SARS-CoV-2 patients in Australia, through respiratory virome characterization. Nasopharyngeal swabs of 92 SARS-CoV-2-positive cases were sequenced using pan-viral hybrid-capture and the Twist Respiratory Virus Panel. In total, 8% of cases were co-infected, with rhinovirus (6%) or influenzavirus (2%). Twist capture also achieved near-complete sequencing (> 90% coverage, > tenfold depth) of the SARS-CoV-2 genome in 95% of specimens with Ct < 30. Our results highlight the importance of assessing all pathogens in symptomatic patients, and the dual-functionality of Twist hybrid-capture, for SARS-CoV-2 whole-genome sequencing without amplicon generation and the simultaneous identification of viral co-infections with ease.


Asunto(s)
/diagnóstico , Coinfección/diagnóstico , Coinfección/virología , Análisis de Secuencia de ADN , /genética , Australia/epidemiología , Coinfección/epidemiología , Biología Computacional , Genoma Viral , Humanos , Sistemas de Lectura Abierta/genética , Reproducibilidad de los Resultados , Secuenciación Completa del Genoma
13.
Viruses ; 13(2)2021 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-33540576

RESUMEN

Infections with SARS-CoV-2 can progress toward multiple clinical outcomes, and the identification of factors associated with disease severity would represent a major advance to guide care and improve prognosis. We tested for associations between SARS-CoV-2 genomic variants from an international cohort of 2508 patients and mortality rates. Findings were validated in a second cohort. Phylogenetic analysis of SARS-CoV-2 genome sequences revealed four well-resolved clades which had significantly different mortality rates, even after adjusting for patient demographic and geographic characteristics. We further identified ten single-nucleotide polymorphisms (SNPs) in the SARS-CoV-2 genome that were associated with patient mortality. Three SNPs remained associated with mortality in a generalized linear model (GLM) that also included patient age, sex, geographic region, and month of sample collection. Multiple SNPs were confirmed in the validation cohort. These SNPs represent targets to assess the mechanisms underlying COVID-19 disease severity and warrant straightforward validation in functional studies.


Asunto(s)
/mortalidad , Genoma Viral , Polimorfismo de Nucleótido Simple , /genética , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Filogenia
14.
Viruses ; 13(2)2021 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-33540713

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally. Although measures to control SARS-CoV-2, namely, vaccination, medication, and chemical disinfectants are being investigated, there is an increase in the demand for auxiliary antiviral approaches using natural compounds. Here we have focused on hydroxytyrosol (HT)-rich aqueous olive pulp extract (HIDROX®) and evaluated its SARS-CoV-2-inactivating activity in vitro. We showed that the HIDROX solution exhibits time- and concentration-dependent SARS-CoV-2-inactivating activities, and that HIDROX has more potent virucidal activity than pure HT. The evaluation of the mechanism of action suggested that both HIDROX and HT induced structural changes in SARS-CoV-2, which changed the molecular weight of the spike proteins. Even though the spike protein is highly glycosylated, this change was induced regardless of the glycosylation status. In addition, HIDROX or HT treatment disrupted the viral genome. Moreover, the HIDROX-containing cream applied on film showed time- and concentration-dependent SARS-CoV-2-inactivating activities. Thus, the HIDROX-containing cream can be applied topically as an antiviral hand cream. Our findings suggest that HIDROX contributes to improving SARS-CoV-2 control measures.


Asunto(s)
Antivirales/farmacología , Olea , Alcohol Feniletílico/análogos & derivados , Extractos Vegetales/farmacología , /efectos de los fármacos , Administración Tópica , Animales , Antivirales/química , Carbohidratos/química , Chlorocebus aethiops , Genoma Viral/efectos de los fármacos , Glicosilación , Pruebas de Sensibilidad Microbiana , Alcohol Feniletílico/administración & dosificación , Alcohol Feniletílico/farmacología , Fosfoproteínas/química , Extractos Vegetales/química , /fisiología , Crema para la Piel , Glicoproteína de la Espiga del Coronavirus/química , Células Vero , Inactivación de Virus/efectos de los fármacos
15.
PLoS One ; 16(2): e0246383, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33544733

RESUMEN

BACKGROUND: In this study, we performed molecular characterization of SARS-CoV-2 strains in Hiroshima and its mutation pattern between the first and second waves of the outbreak. METHOD: A total of 55 nasal swab samples from the first wave in Hiroshima and 13 from the second wave were examined quantitatively by RT-qPCR and qualitatively by nested PCR using specific primers. Four samples from each wave underwent next-generation sequencing and phylogenetic tree analysis including controls and all sequences retrieved in Japan from GISAID and GenBank. Subsequently, mutations were examined. RESULTS: Viral load ranged 7.85 × 101-1.42 × 108 copies/ml. Of 68 samples, one was Asian type-O, 65 were European type-GR, and 2 were undetectable. Phylogenetic tree analysis indicated that Japan was infected with various Asian strains (L, S, V, O) from January through April. By second week of March, European strains (G, GH, GR) had appeared, and GR strains became predominant after mid-March. The first case in Hiroshima was classified as Asian strain O, and the rest were GR strains. Then, second wave of GR strains appeared independently with 11-15 base mutations. Comparing the first- and second-wave GR strains, mutation rate was 1.17-1.36 × 10-3 base substitutions per site per year; in addition, amino acid changes occurred at S1361P and P3371S in ORF1a, A314V in ORF1b, and P151L in N. All seven GR strains were D614G variants with R202K and G203R mutations in N. A single-nucleotide insertion in ORF8 that causes a defect in ORF8 protein was found in one isolate (S66) from the second wave. CONCLUSION: Our findings reveal the evolutionary hierarchy of SARS-CoV-2 in Japan. The predominant D614G variants and a new form of ORF8 deletion in Hiroshima provide the clue for role of viral factor in local outbreaks of SARS-CoV-2.


Asunto(s)
/diagnóstico , Mutación , /genética , Adulto , Anciano , Anciano de 80 o más Años , Brotes de Enfermedades , Femenino , Genoma Viral , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Filogenia , Adulto Joven
16.
mSphere ; 6(1)2021 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-33568452

RESUMEN

Compared to other human coronaviruses, the genetic diversity and evolution of human coronavirus 229E (HCoV-229E) are relatively understudied. We report a fatal case of COVID-19 pneumonia coinfected with HCoV-229E in Hong Kong. Genome sequencing of SARS-CoV-2 and HCoV-229E from a nasopharyngeal sample of the patient showed that the SARS-CoV-2 strain HK13 was most closely related to SARS-CoV-2 type strain Wuhan-Hu-1 (99.99% nucleotide identity), compatible with his recent history of travel to Wuhan. The HCoV-229E strain HK20-42 was most closely related to HCoV-229E strain SC0865 from the United States (99.86% nucleotide identity). To investigate if it may represent a newly emerged HCoV-229E genotype in Hong Kong, we retrieved 41 archived respiratory samples that tested positive for HCoV-229E from 2004 to 2019. Pneumonia and exacerbations of chronic airway diseases were common among infected patients. Complete RdRp, S, and N gene sequencing of the 41 HCoV-229E strains revealed that our contemporary HCoV-229E strains have undergone significant genetic drift with clustering of strains in chronological order. Two novel genogroups were identified, in addition to previously described genogroups 1 to 4, with recent circulating strains including strain HK20-42 belonging to novel genogroup 6. Positive selection was detected in the spike protein and receptor-binding domain, which may be important for viral evolution at the receptor-binding interphase. Molecular dating analysis showed that HCoV-229E shared the most recent common ancestor with bat and camel/alpaca 229E-related viruses at ∼1884, while camel/alpaca viruses had a relatively recent common ancestor at ∼1999. Further studies are required to ascertain the evolutionary origin and path of HCoV-229E.IMPORTANCE Since its first appearance in the 1960s, the genetic diversity and evolution of human coronavirus 229E (HCoV-229E) have been relatively understudied. In this study, we report a fatal case of COVID-19 coinfected with HCoV-229E in Hong Kong. Genome sequencing revealed that our SARS-CoV-2 strain is highly identical to the SARS-CoV-2 strain from Wuhan, compatible with the patient's recent travel history, whereas our HCoV-229E strain in this study is highly identical to a recent strain in the United States. We also retrieved 41 archived HCoV-229E strains from 2004 to 2019 in Hong Kong for sequence analysis. Pneumonia and exacerbations of chronic airway diseases were common diagnoses among the 41 patients. The results showed that HCoV-229E was evolving in chronological order. Two novel genogroups were identified in addition to the four preexisting HCoV-229E genogroups, with recent circulating strains belonging to novel genogroup 6. Molecular clock analysis dated bat-to-human and bat-to-camelid transmission to as early as 1884.


Asunto(s)
/patología , Resfriado Común/patología , Coronavirus Humano 229E/genética , Variación Genética/genética , /genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Niño , Preescolar , Coinfección/virología , Evolución Molecular , Femenino , Genoma Viral/genética , Hong Kong , Humanos , Lactante , Masculino , Persona de Mediana Edad , Dominios Proteicos/genética , Análisis de Secuencia de ARN , Glicoproteína de la Espiga del Coronavirus/genética , Adulto Joven
17.
PLoS One ; 16(1): e0243271, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33428634

RESUMEN

In an outbreak, effective detection of the aetiological agent(s) involved using molecular techniques is key to efficient diagnosis, early prevention and management of the spread. However, sequencing is necessary for mutation monitoring and tracking of clusters of transmission, development of diagnostics and for vaccines and drug development. Many sequencing methods are fast evolving to reduce test turn-around-time and to increase through-put compared to Sanger sequencing method; however, Sanger sequencing remains the gold standard for clinical research sequencing with its 99.99% accuracy This study sought to generate sequence data of SARS-CoV-2 using Sanger sequencing method and to characterize them for possible site(s) of mutations. About 30 pairs of primers were designed, synthesized, and optimized using endpoint PCR to generate amplicons for the full length of the virus. Cycle sequencing using BigDye Terminator v.3.1 and capillary gel electrophoresis on ABI 3130xl genetic analyser were performed according to the manufacturers' instructions. The sequence data generated were assembled and analysed for variations using DNASTAR Lasergene 17 SeqMan Ultra. Total length of 29,760bp of SARS-CoV-2 was assembled from the sample analysed and deposited in GenBank with accession number: MT576584. Blast result of the sequence assembly shows a 99.97% identity with the reference sequence. Variations were noticed at positions: nt201, nt2997, nt14368, nt16535, nt20334, and nt28841-28843, which caused amino acid alterations at the S (aa614) and N (aa203-204) regions. The mutations observed at S and N-gene in this study may be indicative of a gradual changes in the genetic coding of the virus hence, the need for active surveillance of the viral genome.


Asunto(s)
/virología , /genética , Secuencia de Bases , Genoma Viral , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Nigeria/epidemiología , Filogenia , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
18.
Theranostics ; 11(2): 731-753, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33391502

RESUMEN

The coronavirus disease 2019 (COVID-19) is a viral disease caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that affects the respiratory system of infected individuals. COVID-19 spreads between humans through respiratory droplets produced when an infected person coughs or sneezes. The COVID-19 outbreak originated in Wuhan, China at the end of 2019. As of 29 Sept 2020, over 235 countries, areas or territories across the globe reported a total of 33,441,919 confirmed cases, and 1,003,497 confirmed deaths due to COVID-19. Individuals of all ages are at risk for infection, but in most cases disease severity is associated with age and pre-existing diseases that compromise immunity, like cancer. Numerous reports suggest that people with cancer can be at higher risk of severe illness and related deaths from COVID-19. Therefore, managing cancer care under this pandemic is challenging and requires a collaborative multidisciplinary approach for optimal care of cancer patients in hospital settings. In this comprehensive review, we discuss the impact of the COVID-19 pandemic on cancer patients, their care, and treatment. Further, this review covers the SARS-CoV-2 pandemic, genome characterization, COVID-19 pathophysiology, and associated signaling pathways in cancer, and the choice of anticancer agents as repurposed drugs for treating COVID-19.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , /genética , Antineoplásicos/farmacología , /inmunología , Comorbilidad , Reposicionamiento de Medicamentos , Genoma Viral/genética , Humanos , Neoplasias/epidemiología , Pandemias/prevención & control , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Transducción de Señal/inmunología
19.
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