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1.
Cell ; 184(6): 1604-1620, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33740455

RESUMO

Historically, emerging viruses appear constantly and have cost millions of human lives. Currently, climate change and intense globalization have created favorable conditions for viral transmission. Therefore, effective antivirals, especially those targeting the conserved protein in multiple unrelated viruses, such as the compounds targeting RNA-dependent RNA polymerase, are urgently needed to combat more emerging and re-emerging viruses in the future. Here we reviewed the development of antivirals with common targets, including those against the same protein across viruses, or the same viral function, to provide clues for development of antivirals for future epidemics.


Assuntos
Antivirais/uso terapêutico , Doenças Transmissíveis Emergentes/tratamento farmacológico , Doenças Transmissíveis Emergentes/epidemiologia , Terapia de Alvo Molecular/métodos , Pandemias , Viroses/tratamento farmacológico , Viroses/epidemiologia , Vírus/enzimologia , Animais , Antivirais/farmacologia , Doenças Transmissíveis Emergentes/virologia , Humanos , Proteínas do Envelope Viral/antagonistas & inibidores , Viroses/virologia , Internalização do Vírus/efeitos dos fármacos
3.
ACS Synth Biol ; 10(2): 379-390, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33534552

RESUMO

Generating and characterizing immunoreagents to enable studies of novel emerging viruses is an area where ensembles of synthetic genes, recombinant antibody pipelines, and modular antibody-reporter fusion proteins can respond rapidly. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread through the global population causing widespread morbidity, mortality, and socioeconomic chaos. Using SARS-CoV-2 as our model and starting with a gBlocks encoded nucleocapsid (N) gene, we purified recombinant protein from E. coli, to serve as bait for selecting semisynthetic nanobodies from our Nomad single-pot library. Clones were isolated in days and first fused to Gaussia luciferase to determine EC50 in the tens of nM range, and second fused to the ascorbate peroxidase derivative APEX2 for sensitive detection of SARS-CoV-2 infected cells. To generate inherently fluorescent immunoreagents, we introduce novel periplasmic sdAb fusions made with mNeonGreen and mScarlet-I, which were produced at milligram amounts. The fluorescent fusion proteins enabled concise visualization of SARS-CoV-2 N in the cytoplasm but not in the nucleus 24 h post infection, akin to the distribution of SARS-CoV N, thereby validating these useful imaging tools. SdAb reactivity appeared specific to SARS-CoV-2 with very much weaker binding to SARS-CoV, and no noticeable cross-reactivity to a panel of overexpressed human codon optimized N proteins from other CoV. High periplasmic expression levels and in silico immortalization of the nanobody constructs guarantees a cost-effective and reliable source of SARS-CoV-2 immunoreagents. Our proof-of-principle study should be applicable to known and newly emerging CoV to broaden the tools available for their analysis and help safeguard human health in a more proactive than reactive manner.


Assuntos
/epidemiologia , /genética , Sondas Moleculares/genética , Pandemias , /imunologia , Anticorpos Antivirais/genética , Especificidade de Anticorpos/genética , Doenças Transmissíveis Emergentes/virologia , Escherichia coli/genética , Imunofluorescência , Genes Sintéticos , Genes Virais , Células HEK293 , Humanos , Sondas Moleculares/imunologia , Pandemias/prevenção & controle , Biblioteca de Peptídeos , Fosfoproteínas/genética , Fosfoproteínas/imunologia , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Anticorpos de Domínio Único/genética , Biologia Sintética
4.
Onderstepoort J Vet Res ; 88(1): e1-e8, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33567843

RESUMO

Human coronaviruses are known respiratory pathogens associated with a range of respiratory illnesses, and there are considerable morbidity and hospitalisation amongst immune-compromised individuals of all age groups. The emergence of a highly pathogenic human coronavirus in China in 2019 has confirmed the long-held opinion that these viruses are important emerging and re-emerging pathogens. In this review article, we trace the discovery and emergence of coronaviruses (CoVs) over time since they were first reported. The review article will enrich our understanding on the host range, diversity and evolution, transmission of human CoVs and the threat posed by these viruses circulating in animal populations but overtime have spilled over to humans because of the increased proximity between humans and animals.


Assuntos
Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/virologia , Coronavirus/classificação , Animais , Coronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Surtos de Doenças , Especificidade de Hospedeiro , Humanos
5.
Cell Host Microbe ; 29(2): 160-164, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33539765

RESUMO

The emergence of alternate variants of SARS-CoV-2 due to ongoing adaptations in humans and following human-to-animal transmission has raised concern over the efficacy of vaccines against new variants. We describe human-to-animal transmission (zooanthroponosis) of SARS-CoV-2 and its implications for faunal virus persistence and vaccine-mediated immunity.


Assuntos
/veterinária , Doenças Transmissíveis Emergentes/veterinária , Zoonoses/transmissão , Zoonoses/virologia , Animais , /transmissão , Doenças Transmissíveis Emergentes/transmissão , Doenças Transmissíveis Emergentes/virologia , Reservatórios de Doenças/veterinária , Reservatórios de Doenças/virologia , Humanos , Imunidade , Vacinas Virais/imunologia
6.
Viruses ; 13(2)2021 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-33572619

RESUMO

Emerging viral disease is a significant concern, with potential consequences for human, animal and environmental health. Over the past several decades, multiple novel viruses have been found in wildlife species, including reptiles, and often pose a major threat to vulnerable species. However, whilst a large number of viruses have been described in turtles, information on poxvirus in cheloniids remains scarce, with no molecular sequence data available to date. This study characterizes, for the first time, a novel poxvirus, here tentatively designated cheloniid poxvirus 1 (ChePV-1). The affected cutaneous tissue, recovered from a green sea turtle (Chelonia mydas) captured off the Central Queensland coast of Australia, underwent histological examination, transmission electron microscopy (TEM), DNA extraction and genomic sequencing. The novel ChePV-1 was shown to be significantly divergent from other known poxviruses and showed the highest sequence similarity (89.3%) to avipoxviruses (shearwater poxvirus 2 (SWPV2)). This suggests the novel ChePV-1 may have originated from a common ancestor that diverged from an avipoxvirus-like progenitor. The genome contained three predicted unique genes and a further 15 genes being truncated/fragmented compared to SWPV2. This is the first comprehensive study that demonstrates evidence of poxvirus infection in a marine turtle species, as well as a rare example of an avipoxvirus crossing the avian-host barrier. This finding warrants further investigations into poxvirus infections between species in close physical proximity, as well as in vitro and in vivo studies of pathogenesis and disease.


Assuntos
Doenças Transmissíveis Emergentes/veterinária , Infecções por Poxviridae/veterinária , Tartarugas/virologia , Animais , Austrália , Doenças Transmissíveis Emergentes/virologia , Filogenia , Poxviridae/classificação , Poxviridae/genética , Poxviridae/isolamento & purificação , Infecções por Poxviridae/virologia
7.
PLoS Pathog ; 17(1): e1009033, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33411764

RESUMO

The p53 transcription factor plays a key role both in cancer and in the cell-intrinsic response to infections. The ORFEOME project hypothesized that novel p53-virus interactions reside in hitherto uncharacterized, unknown, or hypothetical open reading frames (orfs) of human viruses. Hence, 172 orfs of unknown function from the emerging viruses SARS-Coronavirus, MERS-Coronavirus, influenza, Ebola, Zika (ZIKV), Chikungunya and Kaposi Sarcoma-associated herpesvirus (KSHV) were de novo synthesized, validated and tested in a functional screen of p53 signaling. This screen revealed novel mechanisms of p53 virus interactions and two viral proteins KSHV orf10 and ZIKV NS2A binding to p53. Originally identified as the target of small DNA tumor viruses, these experiments reinforce the notion that all viruses, including RNA viruses, interfere with p53 functions. These results validate this resource for analogous systems biology approaches to identify functional properties of uncharacterized viral proteins, long non-coding RNAs and micro RNAs.


Assuntos
Doenças Transmissíveis Emergentes/virologia , Vírus de RNA/metabolismo , Transdução de Sinais/genética , Proteína Supressora de Tumor p53/metabolismo , Vírus Chikungunya/genética , Vírus Chikungunya/metabolismo , Coronavirus/genética , Coronavirus/metabolismo , Ebolavirus/genética , Ebolavirus/metabolismo , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/metabolismo , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/metabolismo , Fases de Leitura Aberta , Vírus de RNA/genética , Proteína Supressora de Tumor p53/genética , Proteínas não Estruturais Virais/metabolismo , Zika virus/genética , Zika virus/metabolismo
8.
Nat Commun ; 12(1): 151, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420058

RESUMO

Mosquito-borne viruses threaten the Caribbean due to the region's tropical climate and seasonal reception of international tourists. Outbreaks of chikungunya and Zika have demonstrated the rapidity with which these viruses can spread. Concurrently, dengue fever cases have climbed over the past decade. Sustainable disease control measures are urgently needed to quell virus transmission and prevent future outbreaks. Here, to improve upon current control methods, we analyze temporal and spatial patterns of chikungunya, Zika, and dengue outbreaks reported in the Dominican Republic between 2012 and 2018. The viruses that cause these outbreaks are transmitted by Aedes mosquitoes, which are sensitive to seasonal climatological variability. We evaluate whether climate and the spatio-temporal dynamics of dengue outbreaks could explain patterns of emerging disease outbreaks. We find that emerging disease outbreaks were robust to the climatological and spatio-temporal constraints defining seasonal dengue outbreak dynamics, indicating that constant surveillance is required to prevent future health crises.


Assuntos
Febre de Chikungunya/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologia , Dengue/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Doenças Endêmicas/estatística & dados numéricos , Infecção por Zika virus/epidemiologia , Adolescente , Aedes/virologia , Animais , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/transmissão , Febre de Chikungunya/virologia , Vírus Chikungunya/isolamento & purificação , Criança , Pré-Escolar , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/transmissão , Doenças Transmissíveis Emergentes/virologia , Dengue/prevenção & controle , Dengue/transmissão , Dengue/virologia , Vírus da Dengue/isolamento & purificação , Surtos de Doenças/prevenção & controle , República Dominicana/epidemiologia , Doenças Endêmicas/prevenção & controle , Monitoramento Epidemiológico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Controle de Mosquitos , Mosquitos Vetores/virologia , Análise Espaço-Temporal , Adulto Jovem , Zika virus/isolamento & purificação , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
9.
Viruses ; 12(12)2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33316899

RESUMO

Emerging infectious diseases are of great concern to public health, as highlighted by the ongoing coronavirus disease 2019 (COVID-19) pandemic. Such diseases are of particular danger during mass gathering and mass influx events, as large crowds of people in close proximity to each other creates optimal opportunities for disease transmission. The Hashemite Kingdom of Jordan and the Kingdom of Saudi Arabia are two countries that have witnessed mass gatherings due to the arrival of Syrian refugees and the annual Hajj season. The mass migration of people not only brings exotic diseases to these regions but also brings new diseases back to their own countries, e.g., the outbreak of MERS in South Korea. Many emerging pathogens originate in bats, and more than 30 bat species have been identified in these two countries. Some of those bat species are known to carry viruses that cause deadly diseases in other parts of the world, such as the rabies virus and coronaviruses. However, little is known about bats and the pathogens they carry in Jordan and Saudi Arabia. Here, the importance of enhanced surveillance of bat-borne infections in Jordan and Saudi Arabia is emphasized, promoting the awareness of bat-borne diseases among the general public and building up infrastructure and capability to fill the gaps in public health preparedness to prevent future pandemics.


Assuntos
Quirópteros/virologia , Doenças Transmissíveis Emergentes/epidemiologia , Coronavirus/isolamento & purificação , Saúde Pública , Zoonoses/epidemiologia , Animais , Doenças Transmissíveis Emergentes/virologia , Coronavirus/classificação , Coronavirus/patogenicidade , Surtos de Doenças/prevenção & controle , Humanos , Jordânia , Arábia Saudita , Zoonoses/transmissão , Zoonoses/virologia
10.
Front Public Health ; 8: 596944, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33324602

RESUMO

The World Health Organization defines a zoonosis as any infection naturally transmissible from vertebrate animals to humans. The pandemic of Coronavirus disease (COVID-19) caused by SARS-CoV-2 has been classified as a zoonotic disease, however, no animal reservoir has yet been found, so this classification is premature. We propose that COVID-19 should instead be classified an "emerging infectious disease (EID) of probable animal origin." To explore if COVID-19 infection fits our proposed re-categorization vs. the contemporary definitions of zoonoses, we reviewed current evidence of infection origin and transmission routes of SARS-CoV-2 virus and described this in the context of known zoonoses, EIDs and "spill-over" events. Although the initial one hundred COVID-19 patients were presumably exposed to the virus at a seafood Market in China, and despite the fact that 33 of 585 swab samples collected from surfaces and cages in the market tested positive for SARS-CoV-2, no virus was isolated directly from animals and no animal reservoir was detected. Elsewhere, SARS-CoV-2 has been detected in animals including domesticated cats, dogs, and ferrets, as well as captive-managed mink, lions, tigers, deer, and mice confirming zooanthroponosis. Other than circumstantial evidence of zoonotic cases in mink farms in the Netherlands, no cases of natural transmission from wild or domesticated animals have been confirmed. More than 40 million human COVID-19 infections reported appear to be exclusively through human-human transmission. SARS-CoV-2 virus and COVID-19 do not meet the WHO definition of zoonoses. We suggest SARS-CoV-2 should be re-classified as an EID of probable animal origin.


Assuntos
/classificação , Doenças Transmissíveis Emergentes , Zoonoses , Animais , Animais Selvagens , China , Doenças Transmissíveis Emergentes/classificação , Doenças Transmissíveis Emergentes/transmissão , Doenças Transmissíveis Emergentes/virologia , Humanos , Organização Mundial da Saúde , Zoonoses/classificação , Zoonoses/transmissão , Zoonoses/virologia
11.
Viruses ; 13(1)2020 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-33375455

RESUMO

The emergence of arthropod-borne viruses (arboviruses) as linked to land-use changes, especially the growing agricultural intensification and expansion efforts in rural parts of Africa, is of growing health concern. This places an additional burden on health systems as drugs, vaccines, and effective vector-control measures against arboviruses and their vectors remain lacking. An integrated One Health approach holds potential in the control and prevention of arboviruses. Land-use changes favour invasion by invasive alien plants (IAPs) and investigating their impact on mosquito populations may offer a new dimension to our understanding of arbovirus emergence. Of prime importance to understand is how IAPs influence mosquito life-history traits and how this may affect transmission of arboviruses to mammalian hosts, questions that we are exploring in this review. Potential effects of IAPs may be significant, including supporting the proliferation of immature and adult stages of mosquito vectors, providing additional nutrition and suitable microhabitats, and a possible interaction between ingested secondary plant metabolites and arboviruses. We conclude that aspects of vector biology are differentially affected by individual IAPs and that while some plants may have the potential to indirectly increase the risk of transmission of certain arboviruses by their direct interaction with the vectors, the reverse holds for other IAPs. In addition, we highlight priority research areas to improve our understanding of the potential health impacts of IAPs.


Assuntos
Infecções por Arbovirus/epidemiologia , Infecções por Arbovirus/transmissão , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/transmissão , Culicidae/virologia , Espécies Introduzidas , Mosquitos Vetores/virologia , Plantas , Animais , Infecções por Arbovirus/virologia , Doenças Transmissíveis Emergentes/virologia , Ecossistema , Humanos
12.
Discov Med ; 29(158): 201-209, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33007195

RESUMO

Sepsis is an important disorder in intensive care medicine, and the emphasis is not on infections but the imbalance in body reactions and life-threatening organ dysfunction. The infection, the imbalance in the body's reaction, and the deadly organ dysfunction are three aspects of sepsis. Currently, there is still a debate on suitable criteria for the diagnosis of patients with sepsis with continuing changes in the guidelines on sepsis management. Here we summarize recent advances on the definitions, diagnosis, and treatment in the clinical practice of sepsis management in the emergency department. We also highlight future research directions on sepsis. In particular, given the global outbreak of coronavirus disease 2019 (COVID-19), we briefly describe the relationship between COVID-19 and sepsis. How to manage sepsis caused by emerging pathogens such as COVID-19 is a new challenge for care professionals in the emergency department.


Assuntos
Betacoronavirus/patogenicidade , Doenças Transmissíveis Emergentes/terapia , Infecções por Coronavirus/terapia , Tratamento de Emergência/métodos , Pneumonia Viral/terapia , Sepse/terapia , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Doenças Transmissíveis Emergentes/complicações , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Serviço Hospitalar de Emergência/organização & administração , Humanos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Sepse/diagnóstico , Sepse/virologia , Índice de Gravidade de Doença
13.
Front Immunol ; 11: 583077, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101309

RESUMO

Despite the success of vaccination to greatly mitigate or eliminate threat of diseases caused by pathogens, there are still known diseases and emerging pathogens for which the development of successful vaccines against them is inherently difficult. In addition, vaccine development for people with compromised immunity and other pre-existing medical conditions has remained a major challenge. Besides the traditional inactivated or live attenuated, virus-vectored and subunit vaccines, emerging non-viral vaccine technologies, such as viral-like particle and nanoparticle vaccines, DNA/RNA vaccines, and rational vaccine design, offer innovative approaches to address existing challenges of vaccine development. They have also significantly advanced our understanding of vaccine immunology and can guide future vaccine development for many diseases, including rapidly emerging infectious diseases, such as COVID-19, and diseases that have not traditionally been addressed by vaccination, such as cancers and substance abuse. This review provides an integrative discussion of new non-viral vaccine development technologies and their use to address the most fundamental and ongoing challenges of vaccine development.


Assuntos
Betacoronavirus/imunologia , Doenças Transmissíveis Emergentes/prevenção & controle , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/imunologia , Nanopartículas , Vacinação , Vacinas de DNA/imunologia , Vacinas de Subunidades/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia
14.
Front Immunol ; 11: 2130, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013898

RESUMO

In the last decades, a number of infectious viruses have emerged from wildlife or re-emerged, generating serious threats to the global health and to the economy worldwide. Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. Vaccination is probably the most effective tool in helping the immune system to activate protective responses against pathogens, reducing morbidity and mortality, as proven by historical records. Under health emergency conditions, new and alternative approaches in vaccine design and development are imperative for a rapid and massive vaccination coverage, to manage a disease outbreak and curtail the epidemic spread. This review gives an update on the current vaccination strategies for some of the emerging/re-emerging viruses, and discusses challenges and hurdles to overcome for developing efficacious vaccines against future pathogens.


Assuntos
Betacoronavirus/imunologia , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinação , Vacinas Virais/imunologia , Animais , Anticorpos Facilitadores/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Reações Cruzadas/imunologia , Humanos , Imunização Passiva , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Vacinas Atenuadas/imunologia , Vacinas de DNA/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Subunidades/imunologia
16.
Adv Genet ; 106: 119-122, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33081921

RESUMO

WHO's pronouncement of the 2019 novel coronavirus outbreak as a pandemic disease came months after we published a warning that the present deepest minimum of the sunspot cycle would be likely to facilitate the onset of a viral pandemic. During a deep sunspot minimum (deepest in 100 years) such as we are now witnessing, two space related phenomena could have an effect on the disposition of viral disease and potential pandemics. With the weakening of the magnetic field in the Earth's vicinity, there would be a high flux of mutagenic cosmic rays. These processes would be likely to herald the onset of new pandemics. Neutron counts from Moscow Neutron Monitor show that the flux of cosmic rays reaching Earth in 2019 was indeed at a maximum over a timespan of half a century since 1962. It is of interest to note that immediately prior to the first recorded cases of the novel Corona virus in China a peak of cosmic rays was measured as is indicated by the Huon neutron monitor data. Recent research revealed that estimates of the timing of the most recent common ancestor of COVID-19 made with current sequence data point to emergence of the virus in late November 2019 to early December 2019, compatible with the earliest retrospectively confirmed cases and the cosmic ray spike in late November 2019. In our view, this strong cosmic ray spike was in some way connected with the onset of the outbreak.


Assuntos
Evolução Biológica , Infecções por Coronavirus/etiologia , Radiação Cósmica , Pneumonia Viral/etiologia , Atividade Solar , Betacoronavirus/fisiologia , Betacoronavirus/efeitos da radiação , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/etiologia , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/epidemiologia , Radiação Cósmica/efeitos adversos , Planeta Terra , História do Século XXI , Humanos , Nêutrons , Pandemias , Pneumonia Viral/epidemiologia
17.
J Proteome Res ; 19(11): 4259-4274, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-33095583

RESUMO

Emerging and re-emerging infectious diseases due to RNA viruses cause major negative consequences for the quality of life, public health, and overall economic development. Most of the RNA viruses causing illnesses in humans are of zoonotic origin. Zoonotic viruses can directly be transferred from animals to humans through adaptation, followed by human-to-human transmission, such as in human immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and, more recently, SARS coronavirus 2 (SARS-CoV-2), or they can be transferred through insects or vectors, as in the case of Crimean-Congo hemorrhagic fever virus (CCHFV), Zika virus (ZIKV), and dengue virus (DENV). At the present, there are no vaccines or antiviral compounds against most of these viruses. Because proteins possess a vast array of functions in all known biological systems, proteomics-based strategies can provide important insights into the investigation of disease pathogenesis and the identification of promising antiviral drug targets during an epidemic or pandemic. Mass spectrometry technology has provided the capacity required for the precise identification and the sensitive and high-throughput analysis of proteins on a large scale and has contributed greatly to unravelling key protein-protein interactions, discovering signaling networks, and understanding disease mechanisms. In this Review, we present an account of quantitative proteomics and its application in some prominent recent examples of emerging and re-emerging RNA virus diseases like HIV-1, CCHFV, ZIKV, and DENV, with more detail with respect to coronaviruses (MERS-CoV and SARS-CoV) as well as the recent SARS-CoV-2 pandemic.


Assuntos
Doenças Transmissíveis Emergentes , Proteômica , Infecções por Vírus de RNA , Animais , Técnicas de Laboratório Clínico , Doenças Transmissíveis Emergentes/diagnóstico , Doenças Transmissíveis Emergentes/terapia , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/diagnóstico , Humanos , Pandemias , Pneumonia Viral , Infecções por Vírus de RNA/diagnóstico , Infecções por Vírus de RNA/terapia , Infecções por Vírus de RNA/virologia , Vírus de RNA
18.
J Transl Med ; 18(1): 329, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867854

RESUMO

BACKGROUND: The new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first detected in Wuhan (China) in December of 2019 is responsible for the current global pandemic. Phylogenetic analysis revealed that it is similar to other betacoronaviruses, such as SARS-CoV and Middle-Eastern Respiratory Syndrome, MERS-CoV. Its genome is ∼ 30 kb in length and contains two large overlapping polyproteins, ORF1a and ORF1ab that encode for several structural and non-structural proteins. The non-structural protein 1 (nsp1) is arguably the most important pathogenic determinant, and previous studies on SARS-CoV indicate that it is both involved in viral replication and hampering the innate immune system response. Detailed experiments of site-specific mutagenesis and in vitro reconstitution studies determined that the mechanisms of action are mediated by (a) the presence of specific amino acid residues of nsp1 and (b) the interaction between the protein and the host's small ribosomal unit. In fact, substitution of certain amino acids resulted in reduction of its negative effects. METHODS: A total of 17,928 genome sequences were obtained from the GISAID database (December 2019 to July 2020) from patients infected by SARS-CoV-2 from different areas around the world. Genomes alignment was performed using MAFFT (REFF) and the nsp1 genomic regions were identified using BioEdit and verified using BLAST. Nsp1 protein of SARS-CoV-2 with and without deletion have been subsequently modelled using I-TASSER. RESULTS: We identified SARS-CoV-2 genome sequences, from several Countries, carrying a previously unknown deletion of 9 nucleotides in position 686-694, corresponding to the AA position 241-243 (KSF). This deletion was found in different geographical areas. Structural prediction modelling suggests an effect on the C-terminal tail structure. CONCLUSIONS: Modelling analysis of a newly identified deletion of 3 amino acids (KSF) of SARS-CoV-2 nsp1 suggests that this deletion could affect the structure of the C-terminal region of the protein, important for regulation of viral replication and negative effect on host's gene expression. In addition, substitution of the two amino acids (KS) from nsp1 of SARS-CoV was previously reported to revert loss of interferon-alpha expression. The deletion that we describe indicates that SARS-CoV-2 is undergoing profound genomic changes. It is important to: (i) confirm the spreading of this particular viral strain, and potentially of strains with other deletions in the nsp1 protein, both in the population of asymptomatic and pauci-symptomatic subjects, and (ii) correlate these changes in nsp1 with potential decreased viral pathogenicity.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Deleção de Sequência , Proteínas não Estruturais Virais/genética , Sequência de Aminoácidos , Sequência de Bases , Betacoronavirus/patogenicidade , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/epidemiologia , Frequência do Gene , Genoma Viral , Geografia , Humanos , Lisina/genética , Modelos Moleculares , Pandemias/estatística & dados numéricos , Fenilalanina/genética , Pneumonia Viral/epidemiologia , Domínios Proteicos/genética , Serina/genética , Proteínas não Estruturais Virais/química , Virulência/genética , Replicação Viral/genética
19.
J Physiol Anthropol ; 39(1): 29, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32977862

RESUMO

Since 1980, the world has been threatened by different waves of emerging disease epidemics. In the twenty-first century, these diseases have become an increasing global concern because of their health and economic impacts in both developed and resource-constrained countries. It is difficult to stop the occurrence of new pathogens in the future due to the interconnection among humans, animals, and the environment. However, it is possible to face a new disease or to reduce the risk of its spread by implementing better early warning systems and effective disease control and prevention, e.g., effective global surveillance, development of technology for better diagnostics, effective treatments, and vaccines, the global political will to respond to any threats and multidisciplinary collaboration involving all sectors in charge of good health maintenance. In this review, we generally describe some factors related to human activities and show how they can play a role in the transmission and spread of infectious diseases by using some diseases as examples. Additionally, we describe and discuss major factors that are facilitating the spread of the new pandemic known as COVID-19 worldwide.


Assuntos
Betacoronavirus , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/epidemiologia , Atividades Humanas , Pneumonia Viral/epidemiologia , Animais , Mudança Climática , Infecções por Coronavirus/transmissão , Humanos , Internacionalidade , Pandemias , Pneumonia Viral/transmissão
20.
Rev Esp Salud Publica ; 942020 Sep 30.
Artigo em Espanhol | MEDLINE | ID: mdl-32994390

RESUMO

In the midst of the SARS-CoV-2 public-health pandemic emergency, it is important to understand its zoonotic origin and how an animal virus finally infects humans. Identifying the circumstances in which a virus jumps species boundaries to infect humans so productively is objective of this work and will help us to determine the epidemiology and pathogenisis of this agent. Nowadays, it is known that bats serve as reservoir hosts for virus progenitor, but determine the possibility of a potential intermediate host of SARS-CoV-2 is still a challenge. Scientific investigations stablish the natural selection theory as the most probable (natural selection in an animal host before zoonotic transfer or acquired mutations in humans following crossing species barrier). It is necessary to find out how SARS-CoV-2 emerged, its rapidly spreads within a community and the optimal context in which this virus binds to human receptor. One Health is a multisectoral, collaborative and transdisciplinary approach which allows a cooperative working between animal and human health that will help us to introduce some possible control measures that might reduce the spread of the virus; improving sanitary management, identifying new outbreaks and preventing future zoonotic and pandemic events.


Assuntos
Betacoronavirus , Quirópteros/virologia , Doenças Transmissíveis Emergentes/transmissão , Infecções por Coronavirus/transmissão , Reservatórios de Doenças/virologia , Pandemias , Pneumonia Viral/transmissão , Zoonoses/transmissão , Animais , Betacoronavirus/genética , Betacoronavirus/patogenicidade , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Saúde Global , Humanos , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Seleção Genética , Zoonoses/epidemiologia , Zoonoses/virologia
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