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1.
PLoS One ; 16(2): e0246803, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33571320

RESUMO

Niclosamide (NIC) has demonstrated promising in vitro antiviral efficacy against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Though NIC is already FDA-approved, administration of the currently available oral formulation results in systemic drug levels that are too low for the inhibition of SARS-CoV-2. We hypothesized that the co-formulation of NIC with an endogenous protein, human lysozyme (hLYS), could enable the direct aerosol delivery of the drug to the respiratory tract as an alternative to oral delivery, thereby effectively treating COVID-19 by targeting the primary site of SARS-CoV-2 acquisition and spread. To test this hypothesis, we engineered and optimized composite particles containing NIC and hLYS suitable for delivery to the upper and lower airways via dry powder inhaler, nebulizer, and nasal spray. The novel formulation demonstrates potent in vitro and in vivo activity against two coronavirus strains, MERS-CoV and SARS-CoV-2, and may offer protection against methicillin-resistance staphylococcus aureus pneumonia and inflammatory lung damage occurring secondary to SARS-CoV-2 infections. The suitability of the formulation for all stages of the disease and low-cost development approach will ensure rapid clinical development and wide-spread utilization.


Assuntos
Antivirais/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Muramidase/administração & dosagem , Niclosamida/administração & dosagem , Administração por Inalação , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Linhagem Celular , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/instrumentação , Inaladores de Pó Seco , Humanos , Camundongos Transgênicos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Muramidase/farmacologia , Muramidase/uso terapêutico , Sprays Nasais , Niclosamida/farmacologia , Niclosamida/uso terapêutico , /efeitos dos fármacos
2.
PLoS One ; 16(2): e0245072, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33534822

RESUMO

Middle East respiratory syndrome (MERS-COV), first identified in Saudi Arabia, was caused by a novel strain of coronavirus. Outbreaks were recorded from different regions of the world, especially South Korea and the Middle East, and were correlated with a 35% mortality rate. MERS-COV is a single-stranded, positive RNA virus that reaches the host by binding to the receptor of dipeptidyl-peptides. Because of the unavailability of the vaccine available for the protection from MERS-COV infection, the rapid case detection, isolation, infection prevention has been recommended to combat MERS-COV infection. So, vaccines for the treatment of MERS-COV infection need to be developed urgently. A possible antiviral mechanism for preventing MERS-CoV infection has been considered to be MERS-CoV vaccines that elicit unique T-cell responses. In the present study, we incorporated both molecular docking and immunoinformatic approach to introduce a multiepitope vaccine (MEP) against MERS-CoV by selecting 15 conserved epitopes from seven viral proteins such as three structural proteins (envelope, membrane, and nucleoprotein) and four non-structural proteins (ORF1a, ORF8, ORF3, ORF4a). The epitopes, which were examined for non-homologous to host and antigenicity, were selected on the basis of conservation between T-cell, B-cell, and IFN-γ epitopes. The selected epitopes were then connected to the adjuvant (ß-defensin) at the N-terminal through an AAY linker to increase the immunogenic potential. Structural modelling and physiochemical characteristic were applied to the vaccine construct developed. Afterwards the structure has been successfully docked with antigenic receptor, Toll-like receptor 3 (TLR-3) and in-silico cloning ensures that its expression efficiency is legitimate. Nonetheless the MEP presented needs tests to verify its safety and immunogenic profile.


Assuntos
Epitopos/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Proteoma , Vacinas Virais/imunologia , Sequência de Aminoácidos , Sítios de Ligação , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/prevenção & controle , Desenho de Fármacos , Epitopos/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Vacinas de Subunidades/química , Vacinas de Subunidades/imunologia , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/imunologia , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/imunologia , Vacinas Virais/química
3.
PLoS One ; 16(2): e0246150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33534852

RESUMO

A coronavirus pandemic caused by a novel coronavirus (SARS-CoV-2) has spread rapidly worldwide since December 2019. Improved understanding and new strategies to cope with novel coronaviruses are urgently needed. Viruses (especially RNA viruses) encode a limited number and size (length of polypeptide chain) of viral proteins and must interact with the host cell components to control (hijack) the host cell machinery. To achieve this goal, the extensive mimicry of SLiMs in host proteins provides an effective strategy. However, little is known regarding SLiMs in coronavirus proteins and their potential targets in host cells. The objective of this study is to uncover SLiMs in coronavirus proteins that are present within host cells. These SLiMs have a high possibility of interacting with host intracellular proteins and hijacking the host cell machinery for virus replication and dissemination. In total, 1,479 SLiM hits were identified in the 16 proteins of 590 coronaviruses infecting humans. Overall, 106 host proteins were identified that may interact with SLiMs in 16 coronavirus proteins. These SLiM-interacting proteins are composed of many intracellular key regulators, such as receptors, transcription factors and kinases, and may have important contributions to virus replication, immune evasion and viral pathogenesis. A total of 209 pathways containing proteins that may interact with SLiMs in coronavirus proteins were identified. This study uncovers potential mechanisms by which coronaviruses hijack the host cell machinery. These results provide potential therapeutic targets for viral infections.


Assuntos
Infecções por Coronavirus/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Vírus da SARS/metabolismo , Proteínas Virais/metabolismo , Motivos de Aminoácidos , Infecções por Coronavirus/virologia , Bases de Dados de Proteínas , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Filogenia , Domínios e Motivos de Interação entre Proteínas , Proteínas/química , Proteínas/classificação , Vírus da SARS/isolamento & purificação , Transdução de Sinais/genética , Interface Usuário-Computador , Proteínas Virais/química , Proteínas Virais/classificação
4.
Biomed Res Int ; 2021: 8870425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33564683

RESUMO

Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Coronavirus Disease 2019 (COVID-19) infections are the three epidemiological diseases caused by the Coronaviridae family. Perceiving the immune responses in these infections and the escape of viruses could help us design drugs and vaccines for confronting these infections. This review investigates the innate and adaptive immune responses reported in the infections of the three coronaviruses SARS, MERS, and COVID-19. Moreover, the present study can trigger researchers to design and develop new vaccines and drugs based on immune system responses. In conclusion, due to the need for an effective and efficient immune stimulation against coronavirus, a combination of several strategies seems necessary for developing the vaccine.


Assuntos
/imunologia , Infecções por Coronavirus/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Imunidade Adaptativa , Animais , Infecções por Coronavirus/prevenção & controle , Humanos , Imunidade Inata , Síndrome Respiratória Aguda Grave/prevenção & controle
5.
Infect Genet Evol ; 88: 104708, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33421654

RESUMO

The pandemic due to novel coronavirus, SARS-CoV-2 is a serious global concern now. More than thousand new COVID-19 infections are getting reported daily for this virus across the globe. Thus, the medical research communities are trying to find the remedy to restrict the spreading of this virus, while the vaccine development work is still under research in parallel. In such critical situation, not only the medical research community, but also the scientists in different fields like microbiology, pharmacy, bioinformatics and data science are also sharing effort to accelerate the process of vaccine development, virus prediction, forecasting the transmissible probability and reproduction cases of virus for social awareness. With the similar context, in this article, we have studied sequence variability of the virus primarily focusing on three aspects: (a) sequence variability among SARS-CoV-1, MERS-CoV and SARS-CoV-2 in human host, which are in the same coronavirus family, (b) sequence variability of SARS-CoV-2 in human host for 54 different countries and (c) sequence variability between coronavirus family and country specific SARS-CoV-2 sequences in human host. For this purpose, as a case study, we have performed topological analysis of 2391 global genomic sequences of SARS-CoV-2 in association with SARS-CoV-1 and MERS-CoV using an integrated semi-alignment based computational technique. The results of the semi-alignment based technique are experimentally and statistically found similar to alignment based technique and computationally faster. Moreover, the outcome of this analysis can help to identify the nations with homogeneous SARS-CoV-2 sequences, so that same vaccine can be applied to their heterogeneous human population.


Assuntos
/epidemiologia , Infecções por Coronavirus/epidemiologia , Variação Genética , Genoma Viral , Pandemias , Síndrome Respiratória Aguda Grave/epidemiologia , África/epidemiologia , América/epidemiologia , Ásia/epidemiologia , Austrália/epidemiologia , Sequência de Bases , /virologia , Biologia Computacional/métodos , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Europa (Continente)/epidemiologia , Interações Hospedeiro-Patógeno/genética , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Vírus da SARS/genética , Vírus da SARS/patogenicidade , Alinhamento de Sequência , Síndrome Respiratória Aguda Grave/transmissão , Síndrome Respiratória Aguda Grave/virologia
6.
Int Immunopharmacol ; 92: 107051, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33429331

RESUMO

The worldwide outbreak of SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 as a novel human coronavirus, was the worrying news at the beginning of 2020. Since its emergence complicated more than 870,000 individuals and led to more than 43,000 deaths worldwide. Considering to the potential threat of a pandemic and transmission severity of it, there is an urgent need to evaluate and realize this new virus's structure and behavior and the immunopathology of this disease to find potential therapeutic protocols and to design and develop effective vaccines. This disease is able to agitate the response of the immune system in the infected patients, so ARDS, as a common consequence of immunopathological events for infections with Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2, could be the main reason for death. Here, we summarized the immune response and immune evasion characteristics in SARS-CoV, MERS-CoV, and SARS-CoV-2 and therapeutic and prophylactic strategies with a focus on vaccine development and its challenges.


Assuntos
/prevenção & controle , Infecções por Coronavirus/prevenção & controle , Evasão da Resposta Imune/fisiologia , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Síndrome Respiratória Aguda Grave/prevenção & controle , /virologia , Humanos , Imunidade , Vírus da SARS/fisiologia , Vacinas Virais/imunologia
7.
Arch Virol ; 166(3): 675-696, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33462671

RESUMO

The number of descriptions of emerging viruses has grown at an unprecedented rate since the beginning of the 21st century. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is the third highly pathogenic coronavirus that has introduced itself into the human population in the current era, after SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Molecular and cellular studies of the pathogenesis of this novel coronavirus are still in the early stages of research; however, based on similarities of SARS-CoV-2 to other coronaviruses, it can be hypothesized that the NF-κB, cytokine regulation, ERK, and TNF-α signaling pathways are the likely causes of inflammation at the onset of COVID-19. Several drugs have been prescribed and used to alleviate the adverse effects of these inflammatory cellular signaling pathways, and these might be beneficial for developing novel therapeutic modalities against COVID-19. In this review, we briefly summarize alterations of cellular signaling pathways that are associated with coronavirus infection, particularly SARS-CoV and MERS-CoV, and tabulate the therapeutic agents that are currently approved for treating other human diseases.


Assuntos
/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Transdução de Sinais/fisiologia , /tratamento farmacológico , Citocinas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Inflamação/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
8.
Arch Virol ; 166(3): 697-714, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33483791

RESUMO

Coronaviruses are the paradigm of emerging 21st century zoonotic viruses, triggering numerous outbreaks and a severe global health crisis. The current COVID-19 pandemic caused by SARS-CoV-2 has affected more than 51 million people across the globe as of 12 November 2020. The crown-like spikes on the surface of the virion are the unique structural feature of viruses in the family Coronaviridae. The spike (S) protein adopts distinct conformations while mediating entry of the virus into the host. This multifunctional protein mediates the entry process by recognizing its receptor on the host cell, followed by the fusion of the viral membrane with the host cell membrane. This review article focuses on the structural and functional comparison of S proteins of the human betacoronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we review the current state of knowledge about receptor recognition, the membrane fusion mechanism, structural epitopes, and glycosylation sites of the S proteins of these viruses. We further discuss various vaccines and other therapeutics such as monoclonal antibodies, peptides, and small molecules based on the S protein of these three viruses.


Assuntos
/transmissão , Coronavírus da Síndrome Respiratória do Oriente Médio/ultraestrutura , Vírus da SARS/ultraestrutura , Glicoproteína da Espícula de Coronavírus/metabolismo , Ligação Viral , /metabolismo , Antivirais/uso terapêutico , /patologia , Cristalografia por Raios X , Glicosilação , Humanos , Conformação Proteica , Internalização do Vírus
9.
Arch Virol ; 166(3): 715-731, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33492524

RESUMO

Coronaviruses (CoV) are a family of viral pathogens that infect both birds and mammals, including humans. Seven human coronaviruses (HCoV) have been recognized so far. HCoV-229E, -OC43, -NL63, and -HKU1 account for one-third of common colds with mild symptoms. The other three members are severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, and SARS-CoV-2. These viruses are responsible for SARS, MERS, and CoV disease 2019 (COVID-19), respectively. A variety of diagnostic techniques, including chest X-rays, computer tomography (CT) scans, analysis of viral nucleic acids, proteins, or whole virions, and host antibody detection using serological assays have been developed for the detection of these viruses. In this review, we discuss conventional serological tests, such as enzyme-linked immunosorbent assay (ELISA), western blot (WB), immunofluorescence assay (IFA), lateral flow immunoassay (LFIA), and chemiluminescence immunoassay (CLIA), as well as biosensor-based assays that have been developed for diagnosing HCoV-associated diseases since 2003, with an in-depth focus on COVID-19.


Assuntos
Anticorpos Antivirais/sangue , /diagnóstico , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Síndrome Respiratória Aguda Grave/diagnóstico , Anticorpos Antivirais/imunologia , Técnicas Biossensoriais/métodos , Western Blotting/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Imunofluorescência/métodos , Humanos , Medições Luminescentes/métodos , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/virologia
10.
Molecules ; 26(2)2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33467029

RESUMO

The ongoing pandemic of severe acute respiratory syndrome (SARS), caused by the SARS-CoV-2 human coronavirus (HCoV), has brought the international scientific community before a state of emergency that needs to be addressed with intensive research for the discovery of pharmacological agents with antiviral activity. Potential antiviral natural products (NPs) have been discovered from plants of the global biodiversity, including extracts, compounds and categories of compounds with activity against several viruses of the respiratory tract such as HCoVs. However, the scarcity of natural products (NPs) and small-molecules (SMs) used as antiviral agents, especially for HCoVs, is notable. This is a review of 203 publications, which were selected using PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar, evaluates the available literature since the discovery of the first human coronavirus in the 1960s; it summarizes important aspects of structure, function, and therapeutic targeting of HCoVs as well as NPs (19 total plant extracts and 204 isolated or semi-synthesized pure compounds) with anti-HCoV activity targeting viral and non-viral proteins, while focusing on the advances on the discovery of NPs with anti-SARS-CoV-2 activity, and providing a critical perspective.


Assuntos
Antivirais/farmacologia , Produtos Biológicos/farmacologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Vírus da SARS/efeitos dos fármacos , /efeitos dos fármacos , Antivirais/química , Produtos Biológicos/química , Coronavirus Humano 229E/efeitos dos fármacos , Coronavirus Humano 229E/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Vírus da SARS/química , Proteínas Virais/química
11.
Viruses ; 13(1)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33477902

RESUMO

Coronavirus research has gained tremendous attention because of the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (nCoV or SARS-CoV-2). In this review, we highlight recent studies that provide atomic-resolution structural details important for the development of monoclonal antibodies (mAbs) that can be used therapeutically and prophylactically and for vaccines against SARS-CoV-2. Structural studies with SARS-CoV-2 neutralizing mAbs have revealed a diverse set of binding modes on the spike's receptor-binding domain and N-terminal domain and highlight alternative targets on the spike. We consider this structural work together with mAb effects in vivo to suggest correlations between structure and clinical applications. We also place mAbs against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses in the context of the SARS-CoV-2 spike to suggest features that may be desirable to design mAbs or vaccines capable of conferring broad protection.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , /imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Mapeamento de Epitopos , Epitopos/imunologia , Humanos , Imunização Passiva/métodos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/terapia , Glicoproteína da Espícula de Coronavírus/genética , Vacinas Virais/imunologia , Internalização do Vírus/efeitos dos fármacos
12.
Nat Commun ; 12(1): 216, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431849

RESUMO

While a number of human coronaviruses are believed to be originated from ancestral viruses in bats, it remains unclear if bat coronaviruses are ready to cause direct bat-to-human transmission. Here, we report the isolation of a MERS-related coronavirus, Tylonycteris-bat-CoV-HKU4, from lesser bamboo bats. Tylonycteris-bat-CoV-HKU4 replicates efficiently in human colorectal adenocarcinoma and hepatocarcinoma cells with cytopathic effects, and can utilize human-dipeptidyl-peptidase-4 and dromedary camel-dipeptidyl-peptidase-4 as the receptors for cell entry. Flow cytometry, co-immunoprecipitation and surface plasmon resonance assays show that Tylonycteris-bat-CoV-HKU4-receptor-binding-domain can bind human-dipeptidyl-peptidase-4, dromedary camel-dipeptidyl-peptidase-4, and Tylonycteris pachypus-dipeptidyl-peptidase-4. Tylonycteris-bat-CoV-HKU4 can infect human-dipeptidyl-peptidase-4-transgenic mice by intranasal inoculation with self-limiting disease. Positive virus and inflammatory changes were detected in lungs and brains of infected mice, associated with suppression of antiviral cytokines and activation of proinflammatory cytokines and chemokines. The results suggest that MERS-related bat coronaviruses may overcome species barrier by utilizing dipeptidyl-peptidase-4 and potentially emerge in humans by direct bat-to-human transmission.


Assuntos
Quirópteros/virologia , Infecções por Coronavirus/virologia , Dipeptidil Peptidase 4/metabolismo , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Animais , Encéfalo/patologia , Células CACO-2 , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/transmissão , Citocinas/metabolismo , Dipeptidil Peptidase 4/genética , Células HEK293 , Especificidade de Hospedeiro , Humanos , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética
13.
Forensic Sci Med Pathol ; 17(1): 101-113, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33394313

RESUMO

Modern technologies enable the exchange of information about the expansion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the continually increasing number of the coronavirus disease 2019 (COVID-19) cases almost in real time. The gravity of a current epidemiological situation is represented by the mortality rates, which are scrupulously updated daily. Performing autopsies on patients with either suspected or confirmed COVID-19 is of high importance since these might not only improve clinical management but also reduce the risk of SARS-CoV-2 infection expansion. The following paper aimed to present the most crucial aspects of SARS-CoV-2 infection from the point of view of forensic experts and pathologists, recommendations and safety precautions regarding autopsies, autopsy room requirements, possible techniques, examinations used for effective viral detection, recommendations regarding burials, and gross and microscopic pathological findings of the deceased who died due to SARS-CoV-2 infection. Autopsies remain the gold standard for determining the cause of death. Therefore, it would be beneficial to perform autopsies on patients with both suspected and confirmed COVID-19, especially those with coexisting comorbidities.


Assuntos
Autopsia/normas , Patologia Legal/normas , Controle de Infecções/normas , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Filtros de Ar , Sepultamento , Cadáver , Vestuário , Cremação , Reservatórios de Doenças , Embalsamamento , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Equipamento de Proteção Individual , Radiografia , /patogenicidade , Manejo de Espécimes , Tomografia Computadorizada por Raios X
14.
Nat Commun ; 12(1): 6, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397903

RESUMO

The current practice for diagnosis of COVID-19, based on SARS-CoV-2 PCR testing of pharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk, likely underestimates the true prevalence of infection. Serologic methods can more accurately estimate the disease burden by detecting infections missed by the limited testing performed to date. Here, we describe the validation of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A comparison of antibody profiles detected on the array from control sera collected prior to the SARS-CoV-2 pandemic versus convalescent blood specimens from virologically confirmed COVID-19 cases demonstrates near complete discrimination of these two groups, with improved performance from use of antigen combinations that include both spike protein and nucleoprotein. This array can be used as a diagnostic tool, as an epidemiologic tool to more accurately estimate the disease burden of COVID-19, and as a research tool to correlate antibody responses with clinical outcomes.


Assuntos
Anticorpos Antivirais/sangue , Antígenos Virais/sangue , /imunologia , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , /diagnóstico , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Análise em Microsséries/métodos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Testes de Neutralização , Vírus da SARS/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-33435337

RESUMO

Little is understood of the social and cultural effects of coronaviruses such as coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS-CoV). This systematic review aims to synthesize existing findings (both qualitative and quantitative) that focus on the social and cultural impacts of coronaviruses in order to gain a better understanding of the COVID-19 pandemic. Utilizing a predetermined search strategy, we searched CINAHL, PsycINFO, PubMed, and Web of Science to identify existing (qualitative, quantitative, and mixed-methods) studies pertaining to the coronavirus infections and their intersection with societies and cultures. A narrative synthesis approach was applied to summarize and interpret findings of the study. Stemming from SARS outbreak in 2003, qualitative and quantitative findings (twelve adopted quantitative methods and eight exclusively used qualitative methods) were organized under five topical domains: governance, crisis communication and public knowledge, stigma and discrimination, social compliance of preventive measures, and the social experience of health workers. The selected studies suggest that current societies are not equipped for effective coronavirus response and control. This mixed-methods systematic review demonstrates that the effects of coronaviruses on a society can be debilitating.


Assuntos
/epidemiologia , Infecções por Coronavirus , Cultura , Síndrome Respiratória Aguda Grave , Controle de Doenças Transmissíveis , Infecções por Coronavirus/epidemiologia , Governo , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio , Pandemias , Cooperação do Paciente , Síndrome Respiratória Aguda Grave/epidemiologia , Discriminação Social
16.
Ann Clin Microbiol Antimicrob ; 20(1): 8, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33461573

RESUMO

The Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has gained research attention worldwide, given the current pandemic. Nevertheless, a previous zoonotic and highly pathogenic coronavirus, the Middle East Respiratory Syndrome coronavirus (MERS-CoV), is still causing concern, especially in Saudi Arabia and neighbour countries. The MERS-CoV has been reported from respiratory samples in more than 27 countries, and around 2500 cases have been reported with an approximate fatality rate of 35%. After its emergence in 2012 intermittent, sporadic cases, nosocomial infections and many community clusters of MERS continued to occur in many countries. Human-to-human transmission resulted in the large outbreaks in Saudi Arabia. The inherent genetic variability among various clads of the MERS-CoV might have probably paved the events of cross-species transmission along with changes in the inter-species and intra-species tropism. The current review is drafted using an extensive review of literature on various databases, selecting of publications irrespective of favouring or opposing, assessing the merit of study, the abstraction of data and analysing data. The genome of MERS-CoV contains around thirty thousand nucleotides having seven predicted open reading frames. Spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins are the four main structural proteins. The surface located spike protein (S) of betacoronaviruses has been established to be one of the significant factors in their zoonotic transmission through virus-receptor recognition mediation and subsequent initiation of viral infection. Three regions in Saudi Arabia (KSA), Eastern Province, Riyadh and Makkah were affected severely. The epidemic progression had been the highest in 2014 in Makkah and Riyadh and Eastern Province in 2013. With a lurking epidemic scare, there is a crucial need for effective therapeutic and immunological remedies constructed on sound molecular investigations.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , /genética , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Glicoproteína da Espícula de Coronavírus/genética , /genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/virologia , Surtos de Doenças , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Filogenia , RNA Viral/genética , Arábia Saudita/epidemiologia
17.
JCI Insight ; 6(1)2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33427208

RESUMO

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coupled with a lack of therapeutics, has paralyzed the globe. Although significant effort has been invested in identifying antibodies that block infection, the ability of antibodies to target infected cells through Fc interactions may be vital to eliminate the virus. To explore the role of Fc activity in SARS-CoV-2 immunity, the functional potential of a cross-SARS-reactive antibody, CR3022, was assessed. CR3022 was able to broadly drive antibody effector functions, providing critical immune clearance at entry and upon egress. Using selectively engineered Fc variants, no protection was observed after administration of WT IgG1 in mice or hamsters. Conversely, the functionally enhanced Fc variant resulted in increased pathology in both the mouse and hamster models, causing weight loss in mice and enhanced viral replication and weight loss in the more susceptible hamster model, highlighting the pathological functions of Fc-enhancing mutations. These data point to the critical need for strategic Fc engineering for the treatment of SARS-CoV-2 infection.


Assuntos
Anticorpos Neutralizantes/farmacologia , Imunidade Inata/efeitos dos fármacos , Fragmentos Fc das Imunoglobulinas/genética , Imunoglobulina G/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Anticorpos Monoclonais , Anticorpos Neutralizantes/genética , Anticorpos Neutralizantes/uso terapêutico , /fisiopatologia , Cricetinae , Reações Cruzadas , Epitopos , Humanos , Imunidade Inata/imunologia , Imunoglobulina G/genética , Imunoglobulina G/uso terapêutico , Mesocricetus , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Engenharia de Proteínas , Receptores Fc/imunologia , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia , Células THP-1 , Carga Viral/efeitos dos fármacos , Perda de Peso/efeitos dos fármacos
18.
SAR QSAR Environ Res ; 32(1): 51-70, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33401979

RESUMO

A Förster resonance energy transfer (FRET)-based assay was used to screen the FDA-approved compound library against the MERS-CoV helicase, an essential enzyme for virus replication within the host cell. Five compounds inhibited the helicase activity with submicromolar potencies (IC50, 0.73-1.65 µM) and ten compounds inhibited the enzyme with micromolar potencies (IC50, 19.6-502 µM). The molecular operating environment (MOE) was used to dock the identified inhibitors on the MERS-CoV helicase nucleotide binding. Strong inhibitors docked well in the nucleotide-binding site and established interactions with some of the essential residues. There was a reasonable correlation between the observed IC50 values and the MOE docking scores of the strong inhibitors (r 2 = 0.74), indicating the ability of the in silico docking model to predict the binding of strong inhibitors. In silico docking could be a useful complementary tool used with the FRET-based assay to predict new MERS-CoV helicase inhibitors. The identified inhibitors could potentially be used in the clinical development of new antiviral treatment for MERS-CoV and other coronavirus related diseases, including coronavirus disease 2019 (COVID-19).


Assuntos
Antivirais/química , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , DNA Helicases/efeitos dos fármacos , Inibidores Enzimáticos/farmacocinética , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Humanos , Relação Quantitativa Estrutura-Atividade , Replicação Viral/efeitos dos fármacos
19.
Sci Data ; 8(1): 16, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441564

RESUMO

Our systematic literature collection and annotation identified 106 chemical drugs and 31 antibodies effective against the infection of at least one human coronavirus (including SARS-CoV, SAR-CoV-2, and MERS-CoV) in vitro or in vivo in an experimental or clinical setting. A total of 163 drug protein targets were identified, and 125 biological processes involving the drug targets were significantly enriched based on a Gene Ontology (GO) enrichment analysis. The Coronavirus Infectious Disease Ontology (CIDO) was used as an ontological platform to represent the anti-coronaviral drugs, chemical compounds, drug targets, biological processes, viruses, and the relations among these entities. In addition to new term generation, CIDO also adopted various terms from existing ontologies and developed new relations and axioms to semantically represent our annotated knowledge. The CIDO knowledgebase was systematically analyzed for scientific insights. To support rational drug design, a "Host-coronavirus interaction (HCI) checkpoint cocktail" strategy was proposed to interrupt the important checkpoints in the dynamic HCI network, and ontologies would greatly support the design process with interoperable knowledge representation and reasoning.


Assuntos
Antivirais/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Conjuntos de Dados como Assunto , Desenho de Fármacos , Humanos , Bases de Conhecimento , Coronavírus da Síndrome Respiratória do Oriente Médio , Vírus da SARS
20.
BMC Infect Dis ; 21(1): 84, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468070

RESUMO

BACKGROUND: Diabetes is a risk factor for infection with coronaviruses. This study describes the demographic, clinical data, and outcomes of critically ill patients with diabetes and Middle East Respiratory Syndrome (MERS). METHODS: This retrospective cohort study was conducted at 14 hospitals in Saudi Arabia (September 2012-January 2018). We compared the demographic characteristics, underlying medical conditions, presenting symptoms and signs, management and clinical course, and outcomes of critically ill patients with MERS who had diabetes compared to those with no diabetes. Multivariable logistic regression analysis was performed to determine if diabetes was an independent predictor of 90-day mortality. RESULTS: Of the 350 critically ill patients with MERS, 171 (48.9%) had diabetes. Patients with diabetes were more likely to be older, and have comorbid conditions, compared to patients with no diabetes. They were more likely to present with respiratory failure requiring intubation, vasopressors, and corticosteroids. The median time to clearance of MERS-CoV RNA was similar (23 days (Q1, Q3: 17, 36) in patients with diabetes and 21.0 days (Q1, Q3: 10, 33) in patients with no diabetes). Mortality at 90 days was higher in patients with diabetes (78.9% versus 54.7%, p < 0.0001). Multivariable regression analysis showed that diabetes was an independent risk factor for 90-day mortality (odds ratio, 2.09; 95% confidence interval, 1.18-3.72). CONCLUSIONS: Half of the critically ill patients with MERS have diabetes; which is associated with more severe disease. Diabetes is an independent predictor of mortality among critically patients with MERS.


Assuntos
Infecções por Coronavirus/complicações , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/epidemiologia , Corticosteroides , Adulto , Fatores Etários , Idoso , Líquido da Lavagem Broncoalveolar/virologia , Estudos de Coortes , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Nasofaringe/virologia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Estudos Retrospectivos , Fatores de Risco , Arábia Saudita/epidemiologia , Escarro/virologia , Traqueia/virologia
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