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1.
Vopr Virusol ; 67(2): 115-125, 2022 May 05.
Artigo em Russo | MEDLINE | ID: mdl-35521984

RESUMO

By the end of 2021, about 200 studies on the effect of interferons (IFNs) on the incidence and course of the new coronavirus infection COVID-19 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus) have been reported worldwide, with the number of such studies steadily increasing. This review discusses the main issues of the use of IFN drugs in this disease. The literature search was carried out in the PubMed, Scopus, Cochrane Library, Web of Science, RSCI databases, as well as in the Google Scholar preprint database using the available search queries «MeSH for coronavirus¼, «SARS-CoV-2¼, «IFN drugs¼, and «COVID-19¼. Interferon therapy is indicated for early administration (within the first 5 days of patient admission) in cases of mild to moderate COVID-19 to take advantage of the narrow therapeutic window of IFNs action. Control and suppression of viral replication requires therapy with IFNs and other effective antiviral agents that inhibit the reproduction of SARS-CoV-2 and induce several interferon-stimulated genes (ISG). Type I IFNs (IFN-I) exhibit potent pro-inflammatory properties and activate a wide variety of different cell types that respond to IFNs stimulation and pathogen entry. IFN-III confer local mucosal antiviral immunity without inducing the strong systemic pro-inflammatory responses associated with IFN-I. The use of IFNs drugs in the therapy of new coronavirus infection requires a cautious and differentiated approach, because in severe cases they can aggravate viral pathogenesis by causing excessive intensity of inflammatory reactions. The unique biological properties of substances of this class allow us to consider them as therapeutic agents with significant potential for use in patients with COVID-19.


Assuntos
COVID-19 , Coronaviridae , Interferon Tipo I , Antivirais/farmacologia , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Humanos , Interferon Tipo I/farmacologia , Interferon Tipo I/uso terapêutico , Interferons/uso terapêutico , SARS-CoV-2
2.
Virology ; 570: 123-133, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35398776

RESUMO

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


Assuntos
COVID-19 , Coronaviridae , Nidovirales , Coronaviridae/genética , Evolução Molecular , Humanos , Proteínas de Membrana/genética , Nidovirales/genética , Filogenia , SARS-CoV-2/genética
3.
Cell Rep Med ; 3(3): 100524, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35474743

RESUMO

Recently, a novel dog-origin coronavirus has been found in humans. The low similarity between the receptor-binding domain from this novel virus and other human-infecting coronaviruses in genus Alphacoronavirus suggests it might use a novel receptor or mechanism to enter human cells and also might trigger a novel immune response.


Assuntos
Quirópteros , Coronaviridae , Animais , Cães , Filogenia
4.
Virology ; 570: 1-8, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35306415

RESUMO

Enveloped viruses such as Coronaviridae (CoV) enter the host cell by fusing the viral envelope directly with the plasma membrane (PM) or with the membrane of the endosome. Replication of the CoV genome takes place in membrane compartments formed by rearrangement of the endoplasmic reticulum (ER) membrane network. Budding of these viruses occurs from the ER-Golgi intermediate compartment (ERGIC). The relationship between proteins and various membranes is crucial for the replication cycle of CoVs. The role of transmembrane domains (TMDs) and pre-transmembrane domains (pre-TMD) of viral proteins in this process is gaining more recognition. Here we present a thorough analysis of physico-chemical parameters, such as accessible surface area (ASA), average hydrophobicity (Hav), and contribution of specific amino acids in TMDs and pre-TMDs of single-span membrane proteins of human viruses. We focus on unique properties of these elements in CoV and postulate their role in adaptation to diverse host membranes and regulation of retention of membrane proteins during replication.


Assuntos
Coronaviridae , Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Domínios Proteicos , Proteínas Virais/metabolismo
5.
Vopr Virusol ; 67(1): 69-76, 2022 03 15.
Artigo em Russo | MEDLINE | ID: mdl-35293190

RESUMO

INTRODUCTION: The novel coronavirus infection COVID-19 is a major public health problem worldwide. Several publications show the presence of gastrointestinal (GI) symptoms (nausea, vomiting, and diarrhea) in addition to respiratory disorders.The aim of this study was the monitoring of RNA of COVID-19 pathogen, coronavirus SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) in children hospitalized with acute intestinal infection (AII), with following molecular-genetic characterization of detected strains. MATERIAL AND METHODS: Fecal samples of children with AII hospitalized in infectious hospital of Nizhny Novgorod (Russia) in the period from 01.07.2020 to 31.10.2021 were used as material for the study. Viral RNA detection was performed by real-time polymerase chain reaction (RT-PCR). The nucleotide sequence of S-protein gene fragment was determined by Sanger sequencing. RESULTS AND DISCUSSION: SARS-CoV-2 genetic material was detected in 45 out of 2476 fecal samples. The maximum number of samples containing RNA of the virus occurred in November 2020 (detection rate of 12.2%). In 20.0% of cases, SARS-CoV-2 RNA was detected in combination with rota-, noro-, and adenoviruses. 28 nucleotide sequences of S-protein gene fragment complementary DNA (cDNA) were determined. Phylogenetic analysis showed that the studied SARS-CoV-2 strains belonged to two variants. Analysis of the S-protein amino acid sequence of the strains studied showed the absence of the N501Y mutation in the 2020 samples, which is a marker for variants with a high epidemic potential, called variants of concern (VOC) according to the World Health Organization (WHO) definition (lines Alpha B.1.1.7, Beta B.1.351, Gamma P.1). Delta line variant B.1.617.2 was identified in two samples isolated in September 2021. CONCLUSION: The detection of SARS-CoV-2 RNA in the fecal samples of children with AII, suggesting that the fecal-oral mechanism of pathogen transmission may exist, determines the necessity to optimize its monitoring and to develop an algorithm of actions with patients with signs of AII under the conditions of a novel coronavirus infection pandemic.


Assuntos
COVID-19 , Coronaviridae , COVID-19/diagnóstico , COVID-19/epidemiologia , Criança , Coronaviridae/genética , Humanos , Filogenia , RNA Viral/genética , SARS-CoV-2/genética
6.
Viruses ; 14(2)2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35215769

RESUMO

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


Assuntos
Quirópteros/virologia , Infecções por Coronaviridae/veterinária , Coronaviridae/classificação , Coronaviridae/genética , Reservatórios de Doenças/veterinária , Reservatórios de Doenças/virologia , Filogeografia , Recombinação Genética , Animais , Camboja/epidemiologia , China/epidemiologia , Quirópteros/classificação , Coronaviridae/isolamento & purificação , Infecções por Coronaviridae/epidemiologia , Infecções por Coronaviridae/transmissão , Evolução Molecular , Genoma Viral , Filogenia
8.
Vopr Virusol ; 66(6): 442-451, 2022 01 08.
Artigo em Russo | MEDLINE | ID: mdl-35019251

RESUMO

INTRODUCTION: Verification of histological changes in respiratory system using Syrian (golden) hamsters (Mesocricetus auratus) as experimental model is an important task for preclinical studies of drugs intended for prevention and treatment of the novel coronavirus infection COVID-19.The aim of this work was to study pathological changes of pulmonary tissue in SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) experimental infection in Syrian hamsters. MATERIAL AND METHODS: Male Syrian hamsters weighting 80-100 g were infected by intranasal administration of culture SARS-CoV-2 at dose 4 × 104 TCID50/ml (TCID is tissue culture infectious dose). Animals were euthanatized on 3, 7 and 14 days after infection, with gravimetric registration. The viral load in lungs was measured using the polymerase chain reaction (PCR). Right lung and trachea tissues were stained with hematoxylin-eosin and according to Mallory. RESULTS AND DISCUSSION: The highest viral replicative activity in lungs was determined 3 days after the infection. After 7 days, on a background of the decrease of the viral load in lungs, a pathologically significant increase of the organ's gravimetric parameters was observed. Within 3 to 14 days post-infection, the lung histologic pattern had been showing the development of inflammation with a succession of infiltrative-proliferative, edematousmacrophagal and fibroblastic changes. It was found that initial changes in respiratory epithelium can proceed without paranecrotic interstitial inflammation, while in the formation of multiple lung parenchyma lesions, damage to the epithelium of bronchioles and acinar ducts can be secondary. The appearance of epithelioid large-cell metaplastic epithelium, forming pseudoacinar structures, was noted as a pathomorphological feature specific to SARS-CoV-2 infection in Syrian hamsters. CONCLUSION: As a result of the study, the specific features of the pathology of the respiratory system in SARSCoV-2 infected Syrian hamsters were described. These findings are of practical importance as reference data that can be used for preclinical studies to assess the effectiveness of vaccines and potential drugs.


Assuntos
COVID-19 , Pulmão/patologia , Pulmão/virologia , Mesocricetus , Animais , Coronaviridae , Modelos Animais de Doenças , Inflamação , Masculino , Mesocricetus/imunologia , Mesocricetus/virologia , SARS-CoV-2
9.
Mol Biol (Mosk) ; 56(1): 83-102, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35082260

RESUMO

The COVID-19 pandemic caused by the previously unknown SARS-CoV-2 Betacoronavirus made it extremely important to develop simple and safe cellular systems which allow manipulation of the viral genome and high-throughput screening of its potential inhibitors. In this review, we made an attempt at summarizing the currently existing data on genetic engineering systems used to study not only SARS-CoV-2, but also other viruses from the Coronaviridae family. In addition, the review covers the basic knowledge about the structure and the life cycle of coronaviruses.


Assuntos
COVID-19 , Coronaviridae , Coronaviridae/genética , Engenharia Genética , Humanos , Pandemias , SARS-CoV-2
10.
Nucleic Acids Res ; 50(D1): D765-D770, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34634797

RESUMO

The COVID-19 pandemic has seen unprecedented use of SARS-CoV-2 genome sequencing for epidemiological tracking and identification of emerging variants. Understanding the potential impact of these variants on the infectivity of the virus and the efficacy of emerging therapeutics and vaccines has become a cornerstone of the fight against the disease. To support the maximal use of genomic information for SARS-CoV-2 research, we launched the Ensembl COVID-19 browser; the first virus to be encompassed within the Ensembl platform. This resource incorporates a new Ensembl gene set, multiple variant sets, and annotation from several relevant resources aligned to the reference SARS-CoV-2 assembly. Since the first release in May 2020, the content has been regularly updated using our new rapid release workflow, and tools such as the Ensembl Variant Effect Predictor have been integrated. The Ensembl COVID-19 browser is freely available at https://covid-19.ensembl.org.


Assuntos
COVID-19/virologia , Bases de Dados Genéticas , SARS-CoV-2/genética , Navegador , Coronaviridae/genética , Variação Genética , Genoma Viral , Humanos , Anotação de Sequência Molecular
11.
Oral Dis ; 28 Suppl 1: 858-866, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32475006

RESUMO

Coronaviridae is a family of single-stranded positive enveloped RNA viruses. This article aimed to review the history of these viruses in the last 60 years since their discovery to understand what lessons can be learned from the past. A review of the PubMed database was carried out, describing taxonomy, classification, virology, genetic recombination, host adaptation, and main symptoms related to each type of virus. SARS-CoV-2 is responsible for the ongoing global pandemic, and SARS-CoV and MERS-CoV were responsible for causing severe respiratory illness and regional epidemics in the past while the four other strains of CoVs (229-E OC43, NL63, and HKU1) circulate worldwide and normally only cause mild upper respiratory tract infections. Given the enormous diversity of coronavirus viruses in wildlife and their continuous evolution and adaptation to humans, future outbreaks would undoubtedly occur. Restricting or banning all trade in wild animals in wet markets would be a necessary measure to reduce future zoonotic infections.


Assuntos
COVID-19 , Coronaviridae , Infecções Respiratórias , Zoonoses Virais , Animais , Humanos , SARS-CoV-2
12.
Int J Biol Sci ; 17(14): 3717-3727, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671195

RESUMO

SARS-CoV-2 belongs to the coronavirus family. Comparing genomic features of viral genomes of coronavirus family can improve our understanding about SARS-CoV-2. Here we present the first pan-genome analysis of 3,932 whole genomes of 101 species out of 4 genera from the coronavirus family. We found that a total of 181 genes in the pan-genome of coronavirus family, among which only 3 genes, the S gene, M gene and N gene, are highly conserved. We also constructed a pan-genome from 23,539 whole genomes of SARS-CoV-2. There are 13 genes in total in the SARS-CoV-2 pan-genome. All of the 13 genes are core genes for SARS-CoV-2. The pan-genome of coronaviruses shows a lower level of diversity than the pan-genomes of other RNA viruses, which contain no core gene. The three highly conserved genes in coronavirus family, which are also core genes in SARS-CoV-2 pan-genome, could be potential targets in developing nucleic acid diagnostic reagents with a decreased possibility of cross-reaction with other coronavirus species.


Assuntos
Coronaviridae/genética , Genoma Viral , Filogenia
13.
Viruses ; 13(10)2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34696338

RESUMO

Diverse coronavirus (CoV) strains can infect both humans and animals and produce various diseases. CoVs have caused three epidemics and pandemics in the last two decades, and caused a severe impact on public health and the global economy. Therefore, it is of utmost importance to understand the emergence and evolution of endemic and emerging CoV diversity in humans and animals. For diverse bird species, the Infectious Bronchitis Virus is a significant one, whereas feline enteric and canine coronavirus, recombined to produce feline infectious peritonitis virus, infects wild cats. Bovine and canine CoVs have ancestral relationships, while porcine CoVs, especially SADS-CoV, can cross species barriers. Bats are considered as the natural host of diverse strains of alpha and beta coronaviruses. Though MERS-CoV is significant for both camels and humans, humans are nonetheless affected more severely. MERS-CoV cases have been reported mainly in the Arabic peninsula since 2012. To date, seven CoV strains have infected humans, all descended from animals. The severe acute respiratory syndrome coronaviruses (SARS-CoV and SARS-CoV-2) are presumed to be originated in Rhinolopoid bats that severely infect humans with spillover to multiple domestic and wild animals. Emerging alpha and delta variants of SARS-CoV-2 were detected in pets and wild animals. Still, the intermediate hosts and all susceptible animal species remain unknown. SARS-CoV-2 might not be the last CoV to cross the species barrier. Hence, we recommend developing a universal CoV vaccine for humans so that any future outbreak can be prevented effectively. Furthermore, a One Health approach coronavirus surveillance should be implemented at human-animal interfaces to detect novel coronaviruses before emerging to humans and to prevent future epidemics and pandemics.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/genética , Epidemias/prevenção & controle , Animais , Animais Domésticos/virologia , Animais Selvagens/virologia , Coronaviridae/metabolismo , Coronaviridae/patogenicidade , Genoma Viral/genética , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Pandemias/prevenção & controle , Filogenia , Vírus da SARS/genética , SARS-CoV-2/genética , Zoonoses Virais/epidemiologia , Zoonoses Virais/transmissão
14.
Science ; 374(6567): eabj3624, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34581622

RESUMO

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that 2'-5'-oligoadenylate synthetase 1 (OAS1), through ribonuclease L, potently inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show that a common splice-acceptor single-nucleotide polymorphism (Rs10774671) governs whether patients express prenylated OAS1 isoforms that are membrane-associated and sense-specific regions of SARS-CoV-2 RNAs or if they only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. In hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting that this antiviral defense is a major component of a protective antiviral response.


Assuntos
2',5'-Oligoadenilato Sintetase/genética , 2',5'-Oligoadenilato Sintetase/metabolismo , COVID-19/genética , COVID-19/fisiopatologia , RNA de Cadeia Dupla/metabolismo , RNA Viral/metabolismo , SARS-CoV-2/fisiologia , Regiões 5' não Traduzidas , Células A549 , Animais , COVID-19/enzimologia , COVID-19/imunologia , Quirópteros/genética , Quirópteros/virologia , Coronaviridae/enzimologia , Coronaviridae/genética , Coronaviridae/fisiologia , Endorribonucleases/metabolismo , Humanos , Interferons/imunologia , Isoenzimas/genética , Isoenzimas/metabolismo , Diester Fosfórico Hidrolases/genética , Diester Fosfórico Hidrolases/metabolismo , Polimorfismo de Nucleotídeo Único , Prenilação de Proteína , RNA de Cadeia Dupla/química , RNA de Cadeia Dupla/genética , RNA Viral/química , RNA Viral/genética , Retroelementos , SARS-CoV-2/genética , Índice de Gravidade de Doença , Replicação Viral
15.
Infect Genet Evol ; 95: 105075, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34509646

RESUMO

T-cell-mediated immunity to SARS-CoV-2-derived peptides in individuals unexposed to SARS-CoV-2 has been previously reported. This pre-existing immunity was suggested to largely derive from prior exposure to 'common cold' endemic human coronaviruses (HCoVs). To test this, we characterised the sequence homology of SARS-CoV-2-derived T-cell epitopes reported in the literature across the full proteome of the Coronaviridae family. 54.8% of these epitopes had no homology to any of the HCoVs. Further, the proportion of SARS-CoV-2-derived epitopes with any level of sequence homology to the proteins encoded by any of the coronaviruses tested is well-predicted by their alignment-free phylogenetic distance to SARS-CoV-2 (Pearson's r = -0.958). No coronavirus in our dataset showed a significant excess of T-cell epitope homology relative to the proportion of expected random matches, given their genetic similarity to SARS-CoV-2. Our findings suggest that prior exposure to human or animal-associated coronaviruses cannot completely explain the T-cell repertoire in unexposed individuals that recognise SARS-CoV-2 cross-reactive epitopes.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/imunologia , Coronaviridae/imunologia , Resistência à Doença , Memória Imunológica , SARS-CoV-2/imunologia , Animais , Anticorpos Antivirais/genética , Anticorpos Antivirais/imunologia , Antígenos Virais/genética , Antígenos Virais/imunologia , Doenças Assintomáticas , COVID-19/genética , COVID-19/patologia , COVID-19/virologia , Quirópteros/virologia , Coronaviridae/classificação , Coronaviridae/genética , Coronaviridae/patogenicidade , Reações Cruzadas , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Eutérios/virologia , Humanos , Imunidade Celular , Filogenia , SARS-CoV-2/classificação , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Linfócitos T/imunologia , Linfócitos T/virologia
16.
Virology ; 563: 20-27, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34411808

RESUMO

Viruses of the subfamily Orthocoronavirinae can cause mild to severe disease in people, including COVID-19, MERS and SARS. Their most common natural hosts are bat and bird species, which are mostly split across four virus genera. Molecular clock analyses of orthocoronaviruses suggested the most recent common ancestor of these viruses might have emerged either around 10,000 years ago or, using models accounting for selection, many millions of years. Here, we reassess the evolutionary history of these viruses. We present time-aware phylogenetic analyses of a RNA-dependent RNA polymerase locus from 123 orthocoronaviruses isolated from birds and bats, including those in New Zealand, which were geographically isolated from other bats around 35 million years ago. We used this age, as well as the age of the avian-mammals split, to calibrate the molecular clocks, under the assumption that these ages are applicable to the analyzed viruses. We found that the time to the most recent ancestor common for all orthocoronaviruses is likely 150 or more million years, supporting clock analyses that account for selection.


Assuntos
Aves/virologia , Quirópteros/virologia , Infecções por Coronaviridae/virologia , Coronaviridae , Genoma Viral , Animais , Coronaviridae/classificação , Coronaviridae/genética , Evolução Molecular , Nova Zelândia/epidemiologia
17.
Viruses ; 13(8)2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34452414

RESUMO

Nucleotidylylation is a post-transcriptional modification important for replication in the picornavirus supergroup of RNA viruses, including members of the Caliciviridae, Coronaviridae, Picornaviridae and Potyviridae virus families. This modification occurs when the RNA-dependent RNA polymerase (RdRp) attaches one or more nucleotides to a target protein through a nucleotidyl-transferase reaction. The most characterized nucleotidylylation target is VPg (viral protein genome-linked), a protein linked to the 5' end of the genome in Caliciviridae, Picornaviridae and Potyviridae. The nucleotidylylation of VPg by RdRp is a critical step for the VPg protein to act as a primer for genome replication and, in Caliciviridae and Potyviridae, for the initiation of translation. In contrast, Coronaviridae do not express a VPg protein, but the nucleotidylylation of proteins involved in replication initiation is critical for genome replication. Furthermore, the RdRp proteins of the viruses that perform nucleotidylylation are themselves nucleotidylylated, and in the case of coronavirus, this has been shown to be essential for viral replication. This review focuses on nucleotidylylation within the picornavirus supergroup of viruses, including the proteins that are modified, what is known about the nucleotidylylation process and the roles that these modifications have in the viral life cycle.


Assuntos
Nucleotídeos/metabolismo , Vírus de RNA de Cadeia Positiva/metabolismo , RNA Polimerase Dependente de RNA/metabolismo , Proteínas Virais/metabolismo , Caliciviridae/genética , Caliciviridae/metabolismo , Coronaviridae/genética , Coronaviridae/metabolismo , Genoma Viral , Nidovirales/genética , Nidovirales/metabolismo , Picornaviridae/genética , Picornaviridae/metabolismo , Vírus de RNA de Cadeia Positiva/genética , Potyviridae/genética , Potyviridae/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Replicação Viral
18.
Sci Rep ; 11(1): 16145, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373516

RESUMO

The genetic element s2m has been acquired through horizontal transfer by many distantly related viruses, including the SARS-related coronaviruses. Here we show that s2m is evolutionarily conserved in these viruses. Though several lineages of severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) devoid of the element can be found, these variants seem to have been short lived, indicating that they were less evolutionary fit than their s2m-containing counterparts. On a species-level, however, there do not appear to be any losses and this pattern strongly suggests that the s2m element is essential to virus replication in SARS-CoV-2 and related viruses. Further experiments are needed to elucidate the function of s2m.


Assuntos
Coronaviridae/genética , Sequências Repetitivas Dispersas/genética , RNA Viral/genética , SARS-CoV-2/genética , Replicação Viral/genética , Animais , Sequência de Bases , COVID-19/virologia , Coronaviridae/classificação , Evolução Molecular , Transferência Genética Horizontal , Humanos , Filogenia , SARS-CoV-2/fisiologia , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie
19.
Biomed Res Int ; 2021: 8856018, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239932

RESUMO

Coronaviruses (CoVs) are enveloped nonsegmented positive-sense RNA viruses belonging to the family Coronaviridae that contain the largest genome among RNA viruses. Their genome encodes 4 major structural proteins, and among them, the Spike (S) protein plays a crucial role in determining the viral tropism. It mediates viral attachment to the host cell, fusion to the membranes, and cell entry using cellular proteases as activators. Several in vitro models have been developed to study the CoVs entry, pathogenesis, and possible therapeutic approaches. This article is aimed at summarizing the current knowledge about the use of relevant methodologies and cell lines permissive for CoV life cycle studies. The synthesis of this information can be useful for setting up specific experimental procedures. We also discuss different strategies for inhibiting the binding of the S protein to the cell receptors and the fusion process which may offer opportunities for therapeutic intervention.


Assuntos
Antivirais , Coronaviridae , Modelos Biológicos , Tropismo Viral , Internalização do Vírus , Antivirais/química , Antivirais/farmacologia , COVID-19 , Células Cultivadas , Coronaviridae/efeitos dos fármacos , Coronaviridae/metabolismo , Coronaviridae/patogenicidade , Coronaviridae/fisiologia , Infecções por Coronaviridae , Humanos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo
20.
Viruses ; 13(5)2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34070175

RESUMO

The ongoing coronavirus disease 2019 (COVID-19) pandemic has had devastating health and socio-economic impacts. Human activities, especially at the wildlife interphase, are at the core of forces driving the emergence of new viral agents. Global surveillance activities have identified bats as the natural hosts of diverse coronaviruses, with other domestic and wildlife animal species possibly acting as intermediate or spillover hosts. The African continent is confronted by several factors that challenge prevention and response to novel disease emergences, such as high species diversity, inadequate health systems, and drastic social and ecosystem changes. We reviewed published animal coronavirus surveillance studies conducted in Africa, specifically summarizing surveillance approaches, species numbers tested, and findings. Far more surveillance has been initiated among bat populations than other wildlife and domestic animals, with nearly 26,000 bat individuals tested. Though coronaviruses have been identified from approximately 7% of the total bats tested, surveillance among other animals identified coronaviruses in less than 1%. In addition to a large undescribed diversity, sequences related to four of the seven human coronaviruses have been reported from African bats. The review highlights research gaps and the disparity in surveillance efforts between different animal groups (particularly potential spillover hosts) and concludes with proposed strategies for improved future biosurveillance.


Assuntos
Infecções por Coronavirus/epidemiologia , Monitoramento Epidemiológico/veterinária , África/epidemiologia , Animais , Animais Selvagens/virologia , COVID-19/epidemiologia , Quirópteros/virologia , Coronaviridae/genética , Coronavirus/patogenicidade , Ecossistema , Variação Genética , Genoma Viral , Pandemias , Filogenia , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/genética
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