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1.
Nat Commun ; 11(1): 3523, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32647131

RESUMO

The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN-γ production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.


Assuntos
Anticorpos Neutralizantes/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Nanopartículas/química , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/metabolismo , Anticorpos Facilitadores/imunologia , Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Citocinas/imunologia , Modelos Animais de Doenças , Humanos , Imunidade Celular , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , RNA Viral/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Sintéticas/química , Vacinas Sintéticas/imunologia , Vacinas Virais/química
2.
J Transl Med ; 18(1): 281, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32650788

RESUMO

BACKGROUND: The recent outbreak by SARS-CoV-2 has generated a chaos in global health and economy and claimed/infected a large number of lives. Closely resembling with SARS CoV, the present strain has manifested exceptionally higher degree of spreadability, virulence and stability possibly due to some unidentified mutations. The viral spike glycoprotein is very likely to interact with host Angiotensin-Converting Enzyme 2 (ACE2) and transmits its genetic materials and hijacks host machinery with extreme fidelity for self propagation. Few attempts have been made to develop a suitable vaccine or ACE2 blocker or virus-receptor inhibitor within this short period of time. METHODS: Here, attempt was taken to develop some therapeutic and vaccination strategies with a comparison of spike glycoproteins among SARS-CoV, MERS-CoV and the SARS-CoV-2. We verified their structure quality (SWISS-MODEL, Phyre2, and Pymol) topology (ProFunc), motifs (MEME Suite, GLAM2Scan), gene ontology based conserved domain (InterPro database) and screened several epitopes (SVMTrip) of SARS CoV-2 based on their energetics, IC50 and antigenicity with regard to their possible glycosylation and MHC/paratope binding (Vaxigen v2.0, HawkDock, ZDOCK Server) effects. RESULTS: We screened here few pairs of spike protein epitopic regions and selected their energetic, Inhibitory Concentration50 (IC50), MHC II reactivity and found some of those to be very good target for vaccination. A possible role of glycosylation on epitopic region showed profound effects on epitopic recognition. CONCLUSION: The present work might be helpful for the urgent development of a suitable vaccination regimen against SARS CoV-2.


Assuntos
Betacoronavirus/imunologia , Biologia Computacional/métodos , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Epitopos/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/imunologia , Motivos de Aminoácidos , Sequência de Aminoácidos , Sequência Conservada , Infecções por Coronavirus/prevenção & controle , Glicosilação , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Concentração Inibidora 50 , Anotação de Sequência Molecular , Pandemias , Estrutura Secundária de Proteína , Glicoproteína da Espícula de Coronavírus/química
3.
Vaccine ; 38(34): 5418-5423, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32600908

RESUMO

The World Health Organization declared the COVID-19 disease as a pandemic requiring a rapid response. Through online search, direct communication with network members and an internal survey, engagements of developing countries' vaccine manufacturers' network members in the research and development of COVID-19 vaccines and their capacities in the manufacturing, fill-finish and distribution of vaccines were assessed. Currently, 19 network members engaged in research and development of COVID-19 vaccines, using six principal technology platforms. In addition, an internal survey showed that the number of vaccines supplied collectively by 37 members, in 2018-19, was about 3.5 billion doses annually. Almost a third of network members having vaccines prequalified by the World Health Organization comply with international regulations and mechanisms to distribute vaccines across borders. The use of existing manufacturing, fill-finish and distribution capabilities can support an efficient roll-out of vaccines against COVID-19, while maintaining supply security of existing vaccines for on-going immunization programmes.


Assuntos
Pesquisa Biomédica/organização & administração , Infecções por Coronavirus , Indústria Farmacêutica/organização & administração , Cooperação Internacional , Pandemias , Pneumonia Viral , Vacinas Virais/provisão & distribução , Ensaios Clínicos como Assunto , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Organização Mundial da Saúde
6.
Vaccine ; 38(34): 5430-5435, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32620371

RESUMO

BACKGROUND: Health-seeking behaviors change during pandemics and may increase with regard to illnesses with symptoms similar to the pandemic. The global reaction to COVID-19 may drive interest in vaccines for other diseases. OBJECTIVES: Our study investigated the correlation between global online interest in COVID-19 and interest in CDC-recommended routine vaccines. DESIGN, SETTINGS, MEASUREMENTS: This infodemiology study used Google Trends data to quantify worldwide interest in COVID-19 and CDC-recommended vaccines using the unit search volume index (SVI), which estimates volume of online search activity relative to highest volume of searches within a specified period. SVIs from December 30, 2019 to March 30, 2020 were collected for "coronavirus (Virus)" and compared with SVIs of search terms related to CDC-recommended adult vaccines. To account for seasonal variation, we compared SVIs from December 30, 2019 to March 30, 2020 with SVIs from the same months in 2015 to 2019. We performed country-level analyses in ten COVID-19 hotspots and ten countries with low disease burden. RESULTS: There were significant positive correlations between SVIs for "coronavirus (Virus)" and search terms for pneumococcal (R = 0.89, p < 0.0001) and influenza vaccines (R = 0.93, p < 0.0001) in 2020, which were greater than SVIs for the same terms in 2015-2019 (p = 0.005, p < 0.0001, respectively). Eight in ten COVID-19 hotspots demonstrated significant positive correlations between SVIs for coronavirus and search terms for pneumococcal and influenza vaccines. LIMITATIONS: SVIs estimate relative changes in online interest and do not represent the interest of people with no Internet access. CONCLUSION: A peak in worldwide interest in pneumococcal and influenza vaccines coincided with the COVID-19 pandemic in February and March 2020. Trends are likely not seasonal in origin and may be driven by COVID-19 hotspots. Global events may change public perception about the importance of vaccines. Our findings may herald higher demand for pneumonia and influenza vaccines in the upcoming season.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Vacinas contra Influenza , Armazenamento e Recuperação da Informação/estatística & dados numéricos , Internet , Pandemias/prevenção & controle , Vacinas Pneumocócicas , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Vacinas Virais , Centers for Disease Control and Prevention, U.S. , Educação em Saúde/estatística & dados numéricos , Humanos , Ferramenta de Busca/estatística & dados numéricos , Estados Unidos
7.
Vaccine ; 38(34): 5424-5429, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32620375

RESUMO

The COVID-19 pandemic has not only had a negative impact on people's health and life behavior, but also on economies around the world. At the same time, laboratories and institutions are working hard to obtain a COVID-19 vaccine, which we hope will be available soon. However, there has been no assessment of whether an individual and society value ​​a vaccine monetarily, and what factors determine this value. Therefore, the objective of this research was to estimate the individual's willingness to pay (WTP) for a hypothetical COVID-19 vaccine and, at the same time, find the main factors that determine this valuation. For this, we used the contingent valuation approach, in its single and double-bounded dichotomous choice format, which was based on a hypothetical market for a vaccine. The sample used was obtained through an online survey of n = 566 individuals from Chile. The main results showed that the WTP depends on the preexistence of chronic disease (p≤0.05), knowledge of COVID-19 (p≤0.05), being sick with COVID-19 (p≤0.05), perception of government performance (p≤0.01), employment status (p≤0.01), income (p≤0.01), health care (p≤0.05), adaptation to quarantine with children at home (p≤0.01) and whether the person has recovered from COVID-19 (p≤0.10). According to our discrete choice model in double-bounded dichotomous format, it was concluded that the individuals' WTP is US$184.72 (CI: 165.52-203.92; p < 0.01). This implies a social valuation of approximately US$2232 million, corresponding to 1.09% of the GNP per capita.


Assuntos
Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Opinião Pública , Vacinas Virais , Adulto , Criança , Chile/epidemiologia , Infecções por Coronavirus/economia , Infecções por Coronavirus/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias/economia , Pneumonia Viral/economia , Pneumonia Viral/epidemiologia , Vacinas Virais/economia
8.
J Immunol Res ; 2020: 7201752, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32695833

RESUMO

The recent outbreak of the novel coronavirus disease, COVID-19, has highlighted the threat that highly pathogenic coronaviruses have on global health security and the imminent need to design an effective vaccine for prevention purposes. Although several attempts have been made to develop vaccines against human coronavirus infections since the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2003, there is no available licensed vaccine yet. A better understanding of previous coronavirus vaccine studies may help to design a vaccine for the newly emerged virus, SARS-CoV-2, that may also cover other pathogenic coronaviruses as a potentially universal vaccine. In general, coronavirus spike protein is the major antigen for the vaccine design as it can induce neutralizing antibodies and protective immunity. By considering the high genetic similarity between SARS-CoV and SARS-CoV-2, here, protective immunity against SARS-CoV spike subunit vaccine candidates in animal models has been reviewed to gain advances that can facilitate coronavirus vaccine development in the near future.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Desenho de Fármacos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Avaliação Pré-Clínica de Medicamentos , Drogas em Investigação , Humanos , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Vírus da SARS/genética , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Síndrome Respiratória Aguda Grave/virologia , Glicoproteína da Espícula de Coronavírus/genética , Vacinas de Subunidades/imunologia , Vacinas de Subunidades/uso terapêutico
9.
AIDS Rev ; 22(2): 124-127, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32628223

RESUMO

Following the advent of penicillin as first widely used antibiotic during World War II, viruses have steadily replaced bacteria as major agents of infections, particularly for microorganisms that can spread globally. Good examples are pandemics caused by HIV, hepatitis B, hepatitis C, and nowadays severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus of coronavirus disease (COVID)-19.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Betacoronavirus/imunologia , Preparações de Ação Retardada , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Humanos , Profilaxia Pré-Exposição , Vacinas
10.
Vaccine ; 38(35): 5653-5658, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32651113

RESUMO

The COVID-19 outbreak has become a global pandemic responsible for over 2,000,000 confirmed cases and over 126,000 deaths worldwide. In this study, we examined the immunogenicity of CHO-expressed recombinant SARS-CoV-2 S1-Fc fusion protein in mice, rabbits, and monkeys as a potential candidate for a COVID-19 vaccine. We demonstrate that the S1-Fc fusion protein is extremely immunogenic, as evidenced by strong antibody titers observed by day 7. Strong virus neutralizing activity was observed on day 14 in rabbits immunized with the S1-Fc fusion protein using a pseudovirus neutralization assay. Most importantly, in <20 days and three injections of the S1-Fc fusion protein, two monkeys developed higher virus neutralizing titers than a recovered COVID-19 patient in a live SARS-CoV-2 infection assay. Our data strongly suggests that the CHO-expressed SARS-CoV-2 S1-Fc recombinant protein could be a strong candidate for vaccine development against COVID-19.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Infecções por Coronavirus/imunologia , Fragmentos Fc das Imunoglobulinas/química , Macaca/imunologia , Pneumonia Viral/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/imunologia , Animais , Células CHO , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Cricetulus , Feminino , Células HEK293 , Humanos , Imunização Passiva , Fragmentos Fc das Imunoglobulinas/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Camundongos , Pandemias , Coelhos
11.
Vaccine ; 38(35): 5734-5739, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32653276

RESUMO

Several protein vaccine candidates are among the COVID-19 vaccines in development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of protein vaccines. This will help key stakeholders to assess potential safety issues and understand the benefit-risk of such a vaccine platform. The structured and standardized assessment provided by the template would also help contribute to improved public acceptance and communication of licensed protein vaccines.


Assuntos
Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia , Antígenos Virais/administração & dosagem , Antígenos Virais/efeitos adversos , Antígenos Virais/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Humanos , Segurança do Paciente , Medição de Risco , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Proteínas Virais/administração & dosagem , Proteínas Virais/efeitos adversos , Proteínas Virais/imunologia , Vacinas Virais/administração & dosagem
12.
mSphere ; 5(4)2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669462

RESUMO

Human infection challenge studies involving the intentional infection of research participants with a disease-causing agent have recently been suggested as a means to speed up the search for a vaccine for the ongoing coronavirus disease 2019 (COVID-19) outbreak. Calls for challenge studies, however, rely on the expected social value of these studies. This value represents more than the simple possibility that a successful study will lead to the rapid development and dissemination of vaccines but also some expectation that this will actually occur. I show how this expectation may not be realistic in the current political moment and offer potential ways to make sure that any challenge trials that arise actually achieve their goals.


Assuntos
Pesquisa Biomédica/ética , Pesquisa Biomédica/métodos , Ensaios Clínicos como Assunto/ética , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Betacoronavirus , Ética em Pesquisa , Humanos , Valores Sociais , Vacinas Virais/uso terapêutico
13.
Int J Clin Pharmacol Ther ; 58(8): 417-425, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32646540

RESUMO

AIMS OF THE STUDY: Published data show that the current progression of the COVID-19 pandemic in Heidelberg, Germany, despite the current lockdown, could continue into 2021 and become more severe. We have used the modified Bateman SIZ algorithm to predict the effects of interventional measures to control the COVID-19 pandemic. MATERIALS AND METHODS: Model parameters, e.g., doubling time and rate of decrease in the number of infectious persons were obtained from published reports. Predictions were made for the status quo on June 1, 2020, and for interventional measures obtained for 4 scenarios. These included vaccination of the whole population using a SARS-CoV-2 vaccine having an efficacy of 50% and 100%, mass-testing for COVID-19 coronavirus and application of the Corona-Warn-App. RESULTS: The principle findings were 1) without new measures to control the pandemic, the daily number of infectious persons could reach a peak of > 4,500 daily within 18 months when > 67,000 persons would have been infected. This could be prevented by using a vaccine with 50% efficacy which was almost equally effective as a vaccine with 100% efficacy. Application of the Corona-Warn-App was the most effective method and more effective than testing for COVID-19. The methodology used has been described in detail to enable other researchers to apply the modified Bateman SIZ model to obtain predictions for COVID-19 outbreaks in other regions. Application of the model has been verified by independent investigators using different commercial software packages. CONCLUSION: The modified Bateman SIZ model has been verified and used to predict the course of the COVID-19 pandemic in Heidelberg. Lockdown measures alone are insufficient to control the pandemic during 2021. Vaccination, diagnostic tests, and use of the Corona-Warn-App with quarantine could successfully control the spread of the coronavirus infection in the community. The Corona-Warn-App applied correctly may be the most effective. The model showed that vaccination with 50% efficacy is almost as effective as vaccination with 100% efficacy.


Assuntos
Infecções por Coronavirus/epidemiologia , Modelos Estatísticos , Pneumonia Viral/epidemiologia , Algoritmos , Betacoronavirus , Técnicas de Laboratório Clínico , Controle de Doenças Transmissíveis , Busca de Comunicante/instrumentação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Alemanha , Humanos , Programas de Rastreamento , Aplicativos Móveis , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinação , Vacinas Virais
14.
Recenti Prog Med ; 111(7): 398-401, 2020.
Artigo em Italiano | MEDLINE | ID: mdl-32658877

RESUMO

The SARS-CoV-2 pandemic has lifted the veil about how medical knowledge is produced and disseminated. Action Bias, together with economic, academic and media-related interests, has concurred to generate and spread low-value and even unreliable information about some hypothetical therapeutic interventions for CoViD-19. Not only this "infodemic" has weakened people's ability to make informed health choices, but it also has influenced the process of new evidence generation through the violation of the equipoise principle. The CoViD-19 infodemic has further highlighted the need for reliable health information and for people to enter the process of understanding and promoting valuable research. Through a randomized controlled trial, the Informed Health Choices project has shown that it is not impossible neither quixotic to better orient people about health choices since primary school. Similar competencies should be disseminated to everyone through sources that are selected and validated for their capability of reporting evidence based health information about the effects of treatments.


Assuntos
Betacoronavirus , Disseminação de Informação , Pandemias , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Comunicação , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Tomada de Decisões , Reposicionamento de Medicamentos , Medicina Baseada em Evidências , Necessidades e Demandas de Serviços de Saúde , Humanos , Comportamento de Busca de Informação , Uso Off-Label , Pandemias/prevenção & controle , Educação de Pacientes como Assunto/métodos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto/ética , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Equipolência Terapêutica , Vacinas Virais
15.
Int J Mol Sci ; 21(12)2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32604724

RESUMO

In the 21st century, three highly pathogenic betacoronaviruses have emerged, with an alarming rate of human morbidity and case fatality. Genomic information has been widely used to understand the pathogenesis, animal origin and mode of transmission of coronaviruses in the aftermath of the 2002-2003 severe acute respiratory syndrome (SARS) and 2012 Middle East respiratory syndrome (MERS) outbreaks. Furthermore, genome sequencing and bioinformatic analysis have had an unprecedented relevance in the battle against the 2019-2020 coronavirus disease 2019 (COVID-19) pandemic, the newest and most devastating outbreak caused by a coronavirus in the history of mankind. Here, we review how genomic information has been used to tackle outbreaks caused by emerging, highly pathogenic, betacoronavirus strains, emphasizing on SARS-CoV, MERS-CoV and SARS-CoV-2. We focus on shared genomic features of the betacoronaviruses and the application of genomic information to phylogenetic analysis, molecular epidemiology and the design of diagnostic systems, potential drugs and vaccine candidates.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/virologia , Genoma Viral , Pandemias/prevenção & controle , Pneumonia Viral/virologia , Animais , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Desenho de Fármacos , Genes Virais , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Epidemiologia Molecular , Filogenia , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Vírus da SARS/genética , Síndrome Respiratória Aguda Grave/virologia , Vacinas Virais/genética , Vacinas Virais/imunologia
17.
Tex Med ; 116(6): 19, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32645183

RESUMO

Of all the solutions to the COVID-19 pandemic, a vaccine is the most attractive. With just one shot, people could transform the disease from a global disruptor to an easily manageable public health problem. But vaccines can't be whipped up overnight.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Aprovação de Drogas , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Fatores de Tempo , Vacinas Virais , Infecções por Coronavirus/virologia , Humanos , Vacinação em Massa , Pneumonia Viral/virologia , Texas
19.
Theranostics ; 10(16): 7034-7052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32641977

RESUMO

This review provides an update for the international research community on the cell modeling tools that could accelerate the understanding of SARS-CoV-2 infection mechanisms and could thus speed up the development of vaccines and therapeutic agents against COVID-19. Many bioengineering groups are actively developing frontier tools that are capable of providing realistic three-dimensional (3D) models for biological research, including cell culture scaffolds, microfluidic chambers for the culture of tissue equivalents and organoids, and implantable windows for intravital imaging. Here, we review the most innovative study models based on these bioengineering tools in the context of virology and vaccinology. To make it easier for scientists working on SARS-CoV-2 to identify and apply specific tools, we discuss how they could accelerate the discovery and preclinical development of antiviral drugs and vaccines, compared to conventional models.


Assuntos
Antivirais/isolamento & purificação , Antivirais/farmacologia , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Vacinas Virais/isolamento & purificação , Vacinas Virais/farmacologia , Betacoronavirus/química , Betacoronavirus/genética , Betacoronavirus/imunologia , Bioengenharia/métodos , Bioengenharia/tendências , Reatores Biológicos , Técnicas de Cultura de Células , Simulação por Computador , Infecções por Coronavirus/imunologia , Descoberta de Drogas/métodos , Descoberta de Drogas/tendências , Avaliação de Medicamentos/métodos , Avaliação de Medicamentos/tendências , Farmacorresistência Viral , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Modelos Biológicos , Organoides/citologia , Organoides/virologia , Pneumonia Viral/imunologia , Nanomedicina Teranóstica
20.
Theranostics ; 10(16): 7448-7464, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32642005

RESUMO

The COVID-19 pandemic is an emerging threat to global public health. While our current understanding of COVID-19 pathogenesis is limited, a better understanding will help us develop efficacious treatment and prevention strategies for COVID-19. One potential therapeutic target is angiotensin converting enzyme 2 (ACE2). ACE2 primarily catalyzes the conversion of angiotensin I (Ang I) to a nonapeptide angiotensin or the conversion of angiotensin II (Ang II) to angiotensin 1-7 (Ang 1-7) and has direct effects on cardiac function and multiple organs via counter-regulation of the renin-angiotensin system (RAS). Significant to COVID-19, ACE2 is postulated to serve as a major entry receptor for SARS-CoV-2 in human cells, as it does for SARS-CoV. Many infected individuals develop COVID-19 with fever, cough, and shortness of breath that can progress to pneumonia. Disease progression promotes the activation of immune cells, platelets, and coagulation pathways that can lead to multiple organ failure and death. ACE2 is expressed by epithelial cells of the lungs at high level, a major target of the disease, as seen in post-mortem lung tissue of patients who died with COVID-19, which reveals diffuse alveolar damage with cellular fibromyxoid exudates bilaterally. Comparatively, ACE2 is expressed at low level by vascular endothelial cells of the heart and kidney but may also be targeted by the virus in severe COVID-19 cases. Interestingly, SARS-CoV-2 infection downregulates ACE2 expression, which may also play a critical pathogenic role in COVID-19. Importantly, targeting ACE2/Ang 1-7 axis and blocking ACE2 interaction with the S protein of SARS-CoV-2 to curtail SARS-CoV-2 infection are becoming very attractive therapeutics potential for treatment and prevention of COVID-19. Here, we will discuss the following subtopics: 1) ACE2 as a receptor of SARS-CoV-2; 2) clinical and pathological features of COVID-19; 3) role of ACE2 in the infection and pathogenesis of SARS; 4) potential pathogenic role of ACE2 in COVID-19; 5) animal models for pathological studies and therapeutics; and 6) therapeutics development for COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Receptores Virais/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/química , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Modelos Animais de Doenças , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Camundongos , Modelos Biológicos , Pandemias , Pneumonia Viral/terapia , Sistema Renina-Angiotensina/fisiologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Nanomedicina Teranóstica , Vacinas Virais/isolamento & purificação , Internalização do Vírus
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