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1.
Viruses ; 13(4)2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918914

RESUMO

The virus behind the current pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the etiology of novel coronavirus disease (COVID-19) and poses a critical public health threat worldwide. Effective therapeutics and vaccines against multiple coronaviruses remain unavailable. Single-chain variable fragment (scFv), a recombinant antibody, exhibits broad-spectrum antiviral activity against DNA and RNA viruses owing to its nucleic acid-hydrolyzing property. The antiviral activity of 3D8 scFv against SARS-CoV-2 and other coronaviruses was evaluated in Vero E6 cell cultures. Viral growth was quantified with quantitative RT-qPCR and plaque assay. The nucleic acid-hydrolyzing activity of 3D8 was assessed through abzyme assays of in vitro viral transcripts and cell viability was determined by MTT assay. We found that 3D8 inhibited the replication of SARS-CoV-2, human coronavirus OC43 (HCoV-OC43), and porcine epidemic diarrhea virus (PEDV). Our results revealed the prophylactic and therapeutic effects of 3D8 scFv against SARS-CoV-2 in Vero E6 cells. Immunoblot and plaque assays showed the reduction of coronavirus nucleoproteins and infectious particles, respectively, in 3D8 scFv-treated cells. These data demonstrate the broad-spectrum antiviral activity of 3D8 against SARS-CoV-2 and other coronaviruses. Thus, it could be considered a potential antiviral countermeasure against SARS-CoV-2 and zoonotic coronaviruses.


Assuntos
Antivirais/farmacologia , Anticorpos de Cadeia Única/farmacologia , Animais , /prevenção & controle , Sobrevivência Celular/genética , Chlorocebus aethiops , Coronavirus/efeitos dos fármacos , Coronavirus/fisiologia , Relação Dose-Resposta a Droga , Hidrólise , RNA Viral/metabolismo , Células Vero , Carga Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
2.
Viruses ; 13(3)2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800523

RESUMO

Torovirus (ToV) has recently been classified into the new family Tobaniviridae, although it belonged to the Coronavirus (CoV) family historically. ToVs are associated with enteric diseases in animals and humans. In contrast to CoVs, which are recognised as pathogens of veterinary and medical importance, little attention has been paid to ToVs because their infections are usually asymptomatic or not severe; for a long time, only one equine ToV could be propagated in cultured cells. However, bovine ToVs, which predominantly cause diarrhoea in calves, have been detected worldwide, leading to economic losses. Porcine ToVs have also spread globally; although they have not caused serious economic losses, coinfections with other pathogens can exacerbate their symptoms. In addition, frequent inter- or intra-recombination among ToVs can increase pathogenesis or unpredicted host adaptation. These findings have highlighted the importance of ToVs as pathogens and the need for basic ToV research. Here, we review recent progress in the study of ToV molecular biology including reverse genetics, focusing on the similarities and differences between ToVs and CoVs.


Assuntos
Infecções por Torovirus/virologia , Torovirus/fisiologia , Animais , Coronavirus/genética , Coronavirus/fisiologia , Infecções por Coronavirus/virologia , Humanos , Torovirus/genética
3.
Infect Dis Poverty ; 10(1): 28, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726861

RESUMO

BACKGROUND: Coronaviruses (CoVs) are distributed worldwide and have various susceptible hosts; CoVs infecting humans are called human coronaviruses (HCoVs). Although HCoV-specific drugs are still lacking, many potent targets for drug discovery are being explored, and many vigorously designed clinical trials are being carried out in an orderly manner. The aim of this review was to gain a comprehensive understanding of the current status of drug development against HCoVs, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MAIN TEXT: A scoping review was conducted by electronically searching research studies, reviews, and clinical trials in PubMed and the CNKI. Studies on HCoVs and therapeutic drug discovery published between January 2000 and October 2020 and in English or Chinese were included, and the information was summarized. Of the 3248 studies identified, 159 publication were finally included. Advances in drug development against HCoV, especially SARS-CoV-2, are summarized under three categories: antiviral drugs aimed at inhibiting the HCoV proliferation process, drugs acting on the host's immune system, and drugs derived from plants with potent activity. Furthermore, clinical trials of drugs targeting SARS-CoV-2 are summarized. CONCLUSIONS: During the spread of COVID-19 outbreak, great efforts have been made in therapeutic drug discovery against the virus, although the pharmacological effects and adverse reactions of some drugs under study are still unclear. However, well-designed high-quality studies are needed to further study the effectiveness and safety of these potential drugs so as to provide valid recommendations for better control of the COVID-19 pandemic.


Assuntos
Antivirais/farmacologia , Infecções por Coronavirus/virologia , Coronavirus/efeitos dos fármacos , Coronavirus/fisiologia , Descoberta de Drogas , Antivirais/uso terapêutico , Biomarcadores , /metabolismo , Coronavirus/classificação , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Desenvolvimento de Medicamentos , Descoberta de Drogas/métodos , Regulação Viral da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Medicina Tradicional , Terapia de Alvo Molecular , Replicação Viral/efeitos dos fármacos
4.
Virus Res ; 297: 198382, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33705799

RESUMO

Coronaviruses are a large group of RNA viruses that infect a wide range of animal species. The replication strategy of coronaviruses involves recombination and mutation events that lead to the possibility of cross-species transmission. The high plasticity of the viral receptor due to a continuous modification of the host species habitat may be the cause of cross-species transmission that can turn into a threat to other species including the human population. The successive emergence of highly pathogenic coronaviruses such as the Severe Acute Respiratory Syndrome (SARS) in 2003, the Middle East Respiratory Syndrome Coronavirus in 2012, and the recent SARS-CoV-2 has incentivized a number of studies on the molecular basis of the coronavirus and its pathogenesis. The high degree of interrelatedness between humans and wild and domestic animals and the modification of animal habitats by human urbanization, has favored new viral spreads. Hence, knowledge on the main clinical signs of coronavirus infection in the different hosts and the distinctive molecular characteristics of each coronavirus is essential to prevent the emergence of new coronavirus diseases. The coronavirus infections routinely studied in veterinary medicine must be properly recognized and diagnosed not only to prevent animal disease but also to promote public health.


Assuntos
Infecções por Coronavirus , Coronavirus , Especificidade de Hospedeiro , Animais , Coronavirus/química , Coronavirus/genética , Coronavirus/fisiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Genoma Viral , Humanos , Fases de Leitura Aberta , RNA Viral , Proteínas Virais , Estruturas Virais , /virologia , Montagem de Vírus , Replicação Viral
5.
Nat Commun ; 12(1): 780, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594041

RESUMO

Novel pathogenic coronaviruses - such as SARS-CoV and probably SARS-CoV-2 - arise by homologous recombination between co-infecting viruses in a single cell. Identifying possible sources of novel coronaviruses therefore requires identifying hosts of multiple coronaviruses; however, most coronavirus-host interactions remain unknown. Here, by deploying a meta-ensemble of similarity learners from three complementary perspectives (viral, mammalian and network), we predict which mammals are hosts of multiple coronaviruses. We predict that there are 11.5-fold more coronavirus-host associations, over 30-fold more potential SARS-CoV-2 recombination hosts, and over 40-fold more host species with four or more different subgenera of coronaviruses than have been observed to date at >0.5 mean probability cut-off (2.4-, 4.25- and 9-fold, respectively, at >0.9821). Our results demonstrate the large underappreciation of the potential scale of novel coronavirus generation in wild and domesticated animals. We identify high-risk species for coronavirus surveillance.


Assuntos
Coronavirus/fisiologia , Interações Hospedeiro-Patógeno , Mamíferos/virologia , Animais , Infecções por Coronavirus/virologia , Humanos , Modelos Biológicos , Filogenia , Recombinação Genética/genética , Reprodutibilidade dos Testes
6.
Cell ; 184(2): 476-488.e11, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33412089

RESUMO

Coronavirus disease 2019 (COVID-19) exhibits variable symptom severity ranging from asymptomatic to life-threatening, yet the relationship between severity and the humoral immune response is poorly understood. We examined antibody responses in 113 COVID-19 patients and found that severe cases resulting in intubation or death exhibited increased inflammatory markers, lymphopenia, pro-inflammatory cytokines, and high anti-receptor binding domain (RBD) antibody levels. Although anti-RBD immunoglobulin G (IgG) levels generally correlated with neutralization titer, quantitation of neutralization potency revealed that high potency was a predictor of survival. In addition to neutralization of wild-type SARS-CoV-2, patient sera were also able to neutralize the recently emerged SARS-CoV-2 mutant D614G, suggesting cross-protection from reinfection by either strain. However, SARS-CoV-2 sera generally lacked cross-neutralization to a highly homologous pre-emergent bat coronavirus, WIV1-CoV, which has not yet crossed the species barrier. These results highlight the importance of neutralizing humoral immunity on disease progression and the need to develop broadly protective interventions to prevent future coronavirus pandemics.


Assuntos
Anticorpos Neutralizantes/imunologia , Biomarcadores/análise , /fisiopatologia , Adulto , Anticorpos Neutralizantes/análise , Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Biomarcadores/sangue , /epidemiologia , Comorbidade , Coronavirus/classificação , Coronavirus/fisiologia , Reações Cruzadas , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/análise , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Domínios Proteicos , /fisiologia , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/química , Análise de Sobrevida , Resultado do Tratamento
7.
Public Health Genomics ; 24(1-2): 54-66, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33406522

RESUMO

INTRODUCTION: SARS-CoV-2 is a new type of coronavirus causing a pandemic severe acute respiratory syndrome (SARS-2). Coronaviruses are very diverting genetically and mutate so often periodically. The natural selection of viral mutations may cause host infection selectivity and infectivity. METHODS: This study was aimed to indicate the diversity between human and animal coronaviruses through finding the rate of mutation in each of the spike, nucleocapsid, envelope, and membrane proteins. RESULTS: The mutation rate is abundant in all 4 structural proteins. The most number of statistically significant amino acid mutations were found in spike receptor-binding domain (RBD) which may be because it is responsible for a corresponding receptor binding in a broad range of hosts and host selectivity to infect. Among 17 previously known amino acids which are important for binding of spike to angiotensin-converting enzyme 2 (ACE2) receptor, all of them are conservative among human coronaviruses, but only 3 of them significantly are mutated in animal coronaviruses. A single amino acid aspartate-454, that causes dissociation of the RBD of the spike and ACE2, and F486 which gives the strength of binding with ACE2 remain intact in all coronaviruses. DISCUSSION/CONCLUSION: Observations of this study provided evidence of the genetic diversity and rapid evolution of SARS-CoV-2 as well as other human and animal coronaviruses.


Assuntos
/virologia , Coronavirus , Variação Genética/fisiologia , Proteínas Virais , Animais , Coronavirus/classificação , Coronavirus/genética , Coronavirus/fisiologia , Evolução Molecular , Interações entre Hospedeiro e Microrganismos/genética , Humanos , /fisiologia , Proteínas Virais/genética , Proteínas Virais/metabolismo
8.
J Virol Methods ; 290: 114070, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33497729

RESUMO

Viral infections are one of the main cause of diseases worldwide due to the rising trends of migration, urbanization and global mobility of humans. The outbreak of corona virus diseases caused by SARS-CoV (year 2003), MERS-CoV (year 2012) and SARS-CoV-2 (year 2019) raised global health concerns. The side effects associated with the conventional drugs and increase in cases of anti-microbial resistance have led the researchers to switch to natural sources, especially plants, as they have immense potential to be used as antiviral agents. The aim of the article is to summarize the evidences of the bioactive phytocompounds from different plants as an effective alternative for the treatment of infections caused by coronaviruses. However, the use of most plant compounds succumbs to limitations due to lack of experimental evidences and safety studies. Therefore, further research and studies are required to validate their therapeutic uses for wide application of plant-based medicine, including anti-virals.


Assuntos
Antivirais/farmacologia , Infecções por Coronavirus/virologia , Coronavirus/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Antivirais/química , Antivirais/uso terapêutico , Coronavirus/classificação , Coronavirus/fisiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Genoma Viral , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêutico , Plantas Medicinais/química , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/metabolismo
9.
BMC Biol ; 19(1): 12, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482803

RESUMO

BACKGROUND: Pandemics, even more than other medical problems, require swift integration of knowledge. When caused by a new virus, understanding the underlying biology may help finding solutions. In a setting where there are a large number of loosely related projects and initiatives, we need common ground, also known as a "commons." Wikidata, a public knowledge graph aligned with Wikipedia, is such a commons and uses unique identifiers to link knowledge in other knowledge bases. However, Wikidata may not always have the right schema for the urgent questions. In this paper, we address this problem by showing how a data schema required for the integration can be modeled with entity schemas represented by Shape Expressions. RESULTS: As a telling example, we describe the process of aligning resources on the genomes and proteomes of the SARS-CoV-2 virus and related viruses as well as how Shape Expressions can be defined for Wikidata to model the knowledge, helping others studying the SARS-CoV-2 pandemic. How this model can be used to make data between various resources interoperable is demonstrated by integrating data from NCBI (National Center for Biotechnology Information) Taxonomy, NCBI Genes, UniProt, and WikiPathways. Based on that model, a set of automated applications or bots were written for regular updates of these sources in Wikidata and added to a platform for automatically running these updates. CONCLUSIONS: Although this workflow is developed and applied in the context of the COVID-19 pandemic, to demonstrate its broader applicability it was also applied to other human coronaviruses (MERS, SARS, human coronavirus NL63, human coronavirus 229E, human coronavirus HKU1, human coronavirus OC4).


Assuntos
/patologia , Genômica/métodos , Bases de Conhecimento , Proteômica/métodos , /fisiologia , /metabolismo , Coronavirus/genética , Coronavirus/fisiologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Genoma Viral , Humanos , Internet , Pandemias , Proteínas Virais/genética , Proteínas Virais/metabolismo , Fluxo de Trabalho
10.
Virology ; 554: 75-82, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33387787

RESUMO

Human population growth, climate change, and globalization are accelerating the emergence of novel pathogenic viruses. In the past two decades alone, three such members of the coronavirus family have posed serious threats, spurring intense efforts to understand their biology as a way to identify targetable vulnerabilities. Coronaviruses use a programmed -1 ribosomal frameshift (-1 PRF) mechanism to direct synthesis of their replicase proteins. This is a critical switch in their replication program that can be therapeutically targeted. Here, we discuss how nearly half a century of research into -1 PRF have provided insight into the virological importance of -1 PRF, the molecular mechanisms that drive it, and approaches that can be used to manipulate it towards therapeutic outcomes with particular emphasis on SARS-CoV-2.


Assuntos
Antivirais/farmacologia , Coronavirus/efeitos dos fármacos , Coronavirus/genética , Mudança da Fase de Leitura do Gene Ribossômico/efeitos dos fármacos , Antivirais/química , Antivirais/uso terapêutico , Coronavirus/crescimento & desenvolvimento , Coronavirus/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Mudança da Fase de Leitura do Gene Ribossômico/genética , Mudança da Fase de Leitura do Gene Ribossômico/fisiologia , Regulação Viral da Expressão Gênica , Humanos , Mutação , Conformação de Ácido Nucleico , RNA Viral/química , RNA Viral/genética , RNA Viral/metabolismo , /genética , /fisiologia , Replicação Viral
11.
Cell ; 184(1): 106-119.e14, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33333024

RESUMO

The Coronaviridae are a family of viruses that cause disease in humans ranging from mild respiratory infection to potentially lethal acute respiratory distress syndrome. Finding host factors common to multiple coronaviruses could facilitate the development of therapies to combat current and future coronavirus pandemics. Here, we conducted genome-wide CRISPR screens in cells infected by SARS-CoV-2 as well as two seasonally circulating common cold coronaviruses, OC43 and 229E. This approach correctly identified the distinct viral entry factors ACE2 (for SARS-CoV-2), aminopeptidase N (for 229E), and glycosaminoglycans (for OC43). Additionally, we identified phosphatidylinositol phosphate biosynthesis and cholesterol homeostasis as critical host pathways supporting infection by all three coronaviruses. By contrast, the lysosomal protein TMEM106B appeared unique to SARS-CoV-2 infection. Pharmacological inhibition of phosphatidylinositol kinases and cholesterol homeostasis reduced replication of all three coronaviruses. These findings offer important insights for the understanding of the coronavirus life cycle and the development of host-directed therapies.


Assuntos
/genética , Infecções por Coronavirus/genética , Coronavirus/fisiologia , Estudo de Associação Genômica Ampla , Interações Hospedeiro-Patógeno , /fisiologia , Células A549 , Animais , Vias Biossintéticas/efeitos dos fármacos , Linhagem Celular , Chlorocebus aethiops , Colesterol/biossíntese , Colesterol/metabolismo , Análise por Conglomerados , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Resfriado Comum/genética , Resfriado Comum/virologia , Coronavirus/classificação , Infecções por Coronavirus/virologia , Técnicas de Inativação de Genes , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Camundongos , Fosfatidilinositóis/biossíntese , Células Vero , Internalização do Vírus/efeitos dos fármacos , Replicação Viral
12.
Vet Pathol ; 58(3): 438-452, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33357102

RESUMO

Coronaviruses (CoVs) comprise a large group of positive stranded RNA viruses that infect a diverse host range including birds and mammals. Infection with CoVs typically presents as mild to severe respiratory or enteric disease, but CoVs have the potential to cause significant morbidity or mortality in highly susceptible age groups. CoVs have exhibited a penchant for jumping species barriers throughout history with devastating effects. The emergence of highly pathogenic or infectious CoVs in humans over the past 20 years, including severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and most recently severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underscores the significant threat that CoV spillovers pose to humans. Similar to the emergence of SARS-CoV-2, CoVs have been devastating to commercial animal production over the past century, including infectious bronchitis virus in poultry and bovine CoV, as well as the emergence and reemergence of multiple CoVs in swine including transmissible gastroenteritis virus, porcine epidemic diarrhea virus, and porcine deltacoronavirus. These naturally occurring animal CoV infections provide important examples for understanding CoV disease as many animal CoVs have complex pathogenesis similar to SARS-CoV-2 and can shed light on the ongoing SARS-CoV-2 outbreak. We provide an overview and update regarding selected existing animal CoVs and their primary host species, diseases caused by CoVs, how CoVs jump species, whether these CoVs pose an outbreak risk or risk to humans, and how we can mitigate these risks.


Assuntos
Infecções por Coronavirus/virologia , Coronavirus/fisiologia , Animais , Aves , Coronavirus/classificação , Coronavirus/patogenicidade , Infecções por Coronavirus/transmissão , Modelos Animais de Doenças , Humanos , Mamíferos , Filogenia
13.
Microb Pathog ; 150: 104719, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33373693

RESUMO

The recent outbreak of Covid-19 is posing a severe threat to public health globally. Coronaviruses (CoVs) are the largest known group of positive-sense RNA viruses surviving on an extensive number of natural hosts. CoVs are enveloped and non-segmented viruses with a size between 80 and 120 nm. CoV attachment to the surface receptor and its subsequent entrance into cells is mediated by Spike glycoprotein (S). For enhanced CoV entry and successful pathogenesis of CoV, proteolytic processing and receptor-binding act synergistically for induction of large-scale S conformational changes. The shape, size and orientation of receptor-binding domains in viral attachment proteins are well conserved among viruses of different classes that utilize the same receptor. Therefore, investigations unraveling the distribution of cellular receptors with respect to CoV entry, structural aspects of glycoproteins and related conformational changes are highly significant for understanding virus invasion and infection spread. We present the characteristic features of CoV S-Proteins, their significance for CoVs and related receptor binding activities for pathogenesis and viral survival. We are analyzing the novel role of S-protein of CoVs along with their interactive receptors for improving host immunity and decreasing infection spread. This is hoped that presented information will open new ways in tackling coronavirus, especially for the ongoing epidemic.


Assuntos
Infecções por Coronavirus/virologia , Coronavirus/fisiologia , Glicoproteína da Espícula de Coronavírus/metabolismo , /metabolismo , Animais , Sítios de Ligação , /metabolismo , Coronavirus/genética , Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Humanos , Ligação Proteica , Conformação Proteica , /fisiologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Internalização do Vírus , Replicação Viral
14.
mBio ; 11(5)2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067384

RESUMO

Recent evidence shows that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sensitive to interferons (IFNs). However, the most effective types of IFNs and the underlying antiviral effectors remain to be defined. Here, we show that zinc finger antiviral protein (ZAP), which preferentially targets CpG dinucleotides in viral RNA sequences, restricts SARS-CoV-2. We further demonstrate that ZAP and its cofactors KHNYN and TRIM25 are expressed in human lung cells. Type I, II, and III IFNs all strongly inhibited SARS-CoV-2 and further induced ZAP expression. Comprehensive sequence analyses revealed that SARS-CoV-2 and its closest relatives from horseshoe bats showed the strongest CpG suppression among all known human and bat coronaviruses, respectively. Nevertheless, endogenous ZAP expression restricted SARS-CoV-2 replication in human lung cells, particularly upon treatment with IFN-α or IFN-γ. Both the long and the short isoforms of human ZAP reduced SARS-CoV-2 RNA expression levels, but the former did so with greater efficiency. Finally, we show that the ability to restrict SARS-CoV-2 is conserved in ZAP orthologues of the reservoir bat and potential intermediate pangolin hosts of human coronaviruses. Altogether, our results show that ZAP is an important effector of the innate response against SARS-CoV-2, although this pandemic pathogen emerged from zoonosis of a coronavirus that was preadapted to the low-CpG environment in humans.IMPORTANCE Although interferons inhibit SARS-CoV-2 and have been evaluated for treatment of coronavirus disease 2019 (COVID-19), the most effective types and antiviral effectors remain to be defined. Here, we show that IFN-γ is particularly potent in restricting SARS-CoV-2 and in inducing expression of the antiviral factor ZAP in human lung cells. Knockdown experiments revealed that endogenous ZAP significantly restricts SARS-CoV-2. We further show that CpG dinucleotides which are specifically targeted by ZAP are strongly suppressed in the SARS-CoV-2 genome and that the two closest horseshoe bat relatives of SARS-CoV-2 show the lowest genomic CpG content of all coronavirus sequences available from this reservoir host. Nonetheless, both the short and long isoforms of human ZAP reduced SARS-CoV-2 RNA levels, and this activity was conserved in horseshoe bat and pangolin ZAP orthologues. Our findings indicating that type II interferon is particularly efficient against SARS-CoV-2 and that ZAP restricts this pandemic viral pathogen might promote the development of effective immune therapies against COVID-19.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Ilhas de CpG , Pneumonia Viral/virologia , Proteínas de Ligação a RNA/metabolismo , Animais , Betacoronavirus/classificação , Betacoronavirus/genética , Betacoronavirus/metabolismo , Linhagem Celular , Coronavirus/classificação , Coronavirus/genética , Coronavirus/fisiologia , Expressão Gênica/efeitos dos fármacos , Genoma Viral , Humanos , Interferons/farmacologia , Pandemias , Filogenia , Isoformas de Proteínas , RNA Viral/genética , RNA Viral/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , Replicação Viral/efeitos dos fármacos
15.
Electromagn Biol Med ; 39(4): 433-436, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33016156

RESUMO

To help investigate the relationship between inflammatory and other symptoms of coronavirus and the protein-protein interactions (PPI) that occur between viral proteins and protein molecules of the host cell, I propose that the electrostatic discharge (ESD) exists including corona discharge to lead to ozone gas. I cite evidence in support of this hypothesis. I hope that the proposed will inspire new studies in finding effective treatments and vaccines for individuals with coronavirus disease in 2019. I suggest possible future studies that may lend more credibility to the proposed.


Assuntos
Betacoronavirus/fisiologia , Coronavirus/fisiologia , Modelos Biológicos , Eletricidade Estática , Betacoronavirus/química , Betacoronavirus/patogenicidade , Coronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Sistema de Condução Cardíaco/efeitos dos fármacos , Sistema de Condução Cardíaco/fisiopatologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Hidroxicloroquina/farmacologia , Ozônio/metabolismo , Ozônio/toxicidade , Perda de Ozônio , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Domínios e Motivos de Interação entre Proteínas/fisiologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/fisiologia
16.
Adv Genet ; 106: 75-100, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33081928

RESUMO

The origins and global spread of two recent, yet quite different, pandemic diseases is discussed and reviewed in depth: Candida auris, a eukaryotic fungal disease, and COVID-19 (SARS-CoV-2), a positive strand RNA viral respiratory disease. Both these diseases display highly distinctive patterns of sudden emergence and global spread, which are not easy to understand by conventional epidemiological analysis based on simple infection-driven human- to-human spread of an infectious disease (assumed to jump suddenly and thus genetically, from an animal reservoir). Both these enigmatic diseases make sense however under a Panspermia in-fall model and the evidence consistent with such a model is critically reviewed.


Assuntos
Evolução Biológica , Candidíase/etiologia , Doenças Transmissíveis Emergentes/etiologia , Infecções por Coronavirus/etiologia , Origem da Vida , Pneumonia Viral/etiologia , Animais , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , Candida/isolamento & purificação , Candida/fisiologia , Candidíase/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologia , Coronavirus/isolamento & purificação , Coronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Planeta Terra , Exobiologia , Meio Ambiente Extraterreno , Interações Hospedeiro-Patógeno/fisiologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia
17.
Biochem Soc Trans ; 48(5): 2173-2184, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33119046

RESUMO

The endoplasmic reticulum (ER), with its expansive membranous system and a vast network of chaperones, enzymes, sensors, and ion channels, orchestrates diverse cellular functions, ranging from protein synthesis, folding, secretion, and degradation to lipid biogenesis and calcium homeostasis. Strikingly, some of the functions of the ER are exploited by viruses to promote their life cycles. During entry, viruses must penetrate a host membrane and reach an intracellular destination to express and replicate their genomes. These events lead to the assembly of new viral progenies that exit the host cell, thereby initiating further rounds of infection. In this review, we highlight how three distinct viruses - polyomavirus, flavivirus, and coronavirus - co-opt key functions of the ER to cause infection. We anticipate that illuminating this virus-ER interplay will provide rational therapeutic approaches to combat the virus-induced diseases.


Assuntos
Coronavirus/fisiologia , Retículo Endoplasmático/metabolismo , Flavivirus/fisiologia , Interações Hospedeiro-Patógeno , Polyomavirus/fisiologia , Humanos , Chaperonas Moleculares/metabolismo , Viroses/metabolismo , Viroses/prevenção & controle , Internalização do Vírus , Replicação Viral
18.
Mil Med Res ; 7(1): 49, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054860

RESUMO

The effects of coronaviruses on the respiratory system are of great concern, but their effects on the digestive system receive much less attention. Coronaviruses that infect mammals have shown gastrointestinal pathogenicity and caused symptoms such as diarrhea and vomiting. Available data have shown that human coronaviruses, including the newly emerged SARS-CoV-2, mainly infect the respiratory system and cause symptoms such as cough and fever, while they may generate gastrointestinal symptoms. However, there is little about the relation between coronavirus and digestive system. This review specifically addresses the effects of mammalian and human coronaviruses, including SARS-CoV-2, on the digestive tract, helping to cope with the new virus infection-induced disease, COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Coronavirus , Gastroenteropatias , Pandemias , Pneumonia Viral , Animais , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Coronavirus/classificação , Coronavirus/fisiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Gastroenteropatias/fisiopatologia , Gastroenteropatias/virologia , Trato Gastrointestinal/virologia , Humanos , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia
19.
Viruses ; 12(9)2020 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-32933150

RESUMO

Coronaviruses are enveloped RNA viruses capable of causing respiratory, enteric, or systemic diseases in a variety of mammalian hosts that vary in clinical severity from subclinical to fatal. The host range and tissue tropism are largely determined by the coronaviral spike protein, which initiates cellular infection by promoting fusion of the viral and host cell membranes. Companion animal coronaviruses responsible for causing enteric infection include feline enteric coronavirus, ferret enteric coronavirus, canine enteric coronavirus, equine coronavirus, and alpaca enteric coronavirus, while canine respiratory coronavirus and alpaca respiratory coronavirus result in respiratory infection. Ferret systemic coronavirus and feline infectious peritonitis virus, a mutated feline enteric coronavirus, can lead to lethal immuno-inflammatory systemic disease. Recent human viral pandemics, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and most recently, COVID-19, all thought to originate from bat coronaviruses, demonstrate the zoonotic potential of coronaviruses and their potential to have devastating impacts. A better understanding of the coronaviruses of companion animals, their capacity for cross-species transmission, and the sharing of genetic information may facilitate improved prevention and control strategies for future emerging zoonotic coronaviruses. This article reviews the clinical, epidemiologic, virologic, and pathologic characteristics of nine important coronaviruses of companion animals.


Assuntos
Infecções por Coronavirus/veterinária , Coronavirus/isolamento & purificação , Animais de Estimação/virologia , Animais , Camelídeos Americanos/virologia , Doenças do Gato/epidemiologia , Doenças do Gato/virologia , Gatos/virologia , Quirópteros/virologia , Coronavirus/classificação , Coronavirus/genética , Coronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Reservatórios de Doenças/virologia , Doenças do Cão/epidemiologia , Doenças do Cão/virologia , Cães/virologia , Peritonite Infecciosa Felina/epidemiologia , Peritonite Infecciosa Felina/virologia , Furões/virologia , Variação Genética , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/virologia , Cavalos/virologia , Especificidade de Hospedeiro , Humanos , RNA Viral/genética , Glicoproteína da Espícula de Coronavírus/fisiologia , Replicação Viral , Zoonoses
20.
Proc Natl Acad Sci U S A ; 117(41): 25759-25770, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-32994342

RESUMO

Human coronaviruses OC43 and HKU1 are respiratory pathogens of zoonotic origin that have gained worldwide distribution. OC43 apparently emerged from a bovine coronavirus (BCoV) spillover. All three viruses attach to 9-O-acetylated sialoglycans via spike protein S with hemagglutinin-esterase (HE) acting as a receptor-destroying enzyme. In BCoV, an HE lectin domain promotes esterase activity toward clustered substrates. OC43 and HKU1, however, lost HE lectin function as an adaptation to humans. Replaying OC43 evolution, we knocked out BCoV HE lectin function and performed forced evolution-population dynamics analysis. Loss of HE receptor binding selected for second-site mutations in S, decreasing S binding affinity by orders of magnitude. Irreversible HE mutations led to cooperativity in virus swarms with low-affinity S minority variants sustaining propagation of high-affinity majority phenotypes. Salvageable HE mutations induced successive second-site substitutions in both S and HE. Apparently, S and HE are functionally interdependent and coevolve to optimize the balance between attachment and release. This mechanism of glycan-based receptor usage, entailing a concerted, fine-tuned activity of two envelope protein species, is unique among CoVs, but reminiscent of that of influenza A viruses. Apparently, general principles fundamental to virion-sialoglycan interactions prompted convergent evolution of two important groups of human and animal pathogens.


Assuntos
Coronavirus/fisiologia , Hemaglutininas Virais/genética , Glicoproteína da Espícula de Coronavírus/genética , Proteínas Virais de Fusão/genética , Vírion/metabolismo , Animais , Evolução Biológica , Linhagem Celular , Coronavirus/genética , Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Coronavirus Humano OC43/genética , Coronavirus Humano OC43/metabolismo , Coronavirus Humano OC43/fisiologia , Coronavirus Bovino/genética , Coronavirus Bovino/metabolismo , Coronavirus Bovino/fisiologia , Hemaglutininas Virais/química , Hemaglutininas Virais/metabolismo , Humanos , Lectinas/genética , Lectinas/metabolismo , Camundongos , Mutação , Ligação Proteica , Domínios Proteicos , Receptores Virais/metabolismo , Seleção Genética , Ácidos Siálicos/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Proteínas Virais de Fusão/química , Proteínas Virais de Fusão/metabolismo , Vírion/genética , Ligação Viral , Liberação de Vírus
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