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1.
Signal Transduct Target Ther ; 6(1): 340, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504054

RESUMO

As COVID-19 continues to spread rapidly worldwide and variants continue to emerge, the development and deployment of safe and effective vaccines are urgently needed. Here, we developed an mRNA vaccine based on the trimeric receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein fused to ferritin-formed nanoparticles (TF-RBD). Compared to the trimeric form of the RBD mRNA vaccine (T-RBD), TF-RBD delivered intramuscularly elicited robust and durable humoral immunity as well as a Th1-biased cellular response. After further challenge with live SARS-CoV-2, immunization with a two-shot low-dose regimen of TF-RBD provided adequate protection in hACE2-transduced mice. In addition, the mRNA template of TF-RBD was easily and quickly engineered into a variant vaccine to address SARS-CoV-2 mutations. The TF-RBD multivalent vaccine produced broad-spectrum neutralizing antibodies against Alpha (B.1.1.7) and Beta (B.1.351) variants. This mRNA vaccine based on the encoded self-assembled nanoparticle-based trimer RBD provides a reference for the design of mRNA vaccines targeting SARS-CoV-2.


Assuntos
Vacinas contra COVID-19 , COVID-19/prevenção & controle , Nanopartículas , SARS-CoV-2/imunologia , Vacinas Sintéticas , Animais , COVID-19/imunologia , COVID-19/patologia , Vacinas contra COVID-19/química , Vacinas contra COVID-19/farmacologia , Chlorocebus aethiops , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Transgênicos , Nanopartículas/química , Nanopartículas/uso terapêutico , Células Th1/imunologia , Células Th1/patologia , Vacinas Sintéticas/química , Vacinas Sintéticas/imunologia , Células Vero
2.
Nat Commun ; 12(1): 5573, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34552095

RESUMO

To support COVID-19 pandemic planning, we develop a model-inference system to estimate epidemiological properties of new SARS-CoV-2 variants of concern using case and mortality data while accounting for under-ascertainment, disease seasonality, non-pharmaceutical interventions, and mass-vaccination. Applying this system to study three variants of concern, we estimate that B.1.1.7 has a 46.6% (95% CI: 32.3-54.6%) transmissibility increase but nominal immune escape from protection induced by prior wild-type infection; B.1.351 has a 32.4% (95% CI: 14.6-48.0%) transmissibility increase and 61.3% (95% CI: 42.6-85.8%) immune escape; and P.1 has a 43.3% (95% CI: 30.3-65.3%) transmissibility increase and 52.5% (95% CI: 0-75.8%) immune escape. Model simulations indicate that B.1.351 and P.1 could outcompete B.1.1.7 and lead to increased infections. Our findings highlight the importance of preventing the spread of variants of concern, via continued preventive measures, prompt mass-vaccination, continued vaccine efficacy monitoring, and possible updating of vaccine formulations to ensure high efficacy.


Assuntos
COVID-19/epidemiologia , COVID-19/transmissão , Modelos Teóricos , SARS-CoV-2/patogenicidade , Adolescente , Adulto , Idoso , Brasil/epidemiologia , COVID-19/mortalidade , COVID-19/virologia , Vacinas contra COVID-19/farmacologia , Criança , Pré-Escolar , Humanos , Evasão da Resposta Imune , Incidência , Lactente , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , África do Sul/epidemiologia , Reino Unido/epidemiologia , Adulto Jovem
3.
Comput Math Methods Med ; 2021: 1250129, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497662

RESUMO

We formulate and theoretically analyze a mathematical model of COVID-19 transmission mechanism incorporating vital dynamics of the disease and two key therapeutic measures-vaccination of susceptible individuals and recovery/treatment of infected individuals. Both the disease-free and endemic equilibrium are globally asymptotically stable when the effective reproduction number R 0(v) is, respectively, less or greater than unity. The derived critical vaccination threshold is dependent on the vaccine efficacy for disease eradication whenever R 0(v) > 1, even if vaccine coverage is high. Pontryagin's maximum principle is applied to establish the existence of the optimal control problem and to derive the necessary conditions to optimally mitigate the spread of the disease. The model is fitted with cumulative daily Senegal data, with a basic reproduction number R 0 = 1.31 at the onset of the epidemic. Simulation results suggest that despite the effectiveness of COVID-19 vaccination and treatment to mitigate the spread of COVID-19, when R 0(v) > 1, additional efforts such as nonpharmaceutical public health interventions should continue to be implemented. Using partial rank correlation coefficients and Latin hypercube sampling, sensitivity analysis is carried out to determine the relative importance of model parameters to disease transmission. Results shown graphically could help to inform the process of prioritizing public health intervention measures to be implemented and which model parameter to focus on in order to mitigate the spread of the disease. The effective contact rate b, the vaccine efficacy ε, the vaccination rate v, the fraction of exposed individuals who develop symptoms, and, respectively, the exit rates from the exposed and the asymptomatic classes σ and ϕ are the most impactful parameters.


Assuntos
COVID-19/prevenção & controle , COVID-19/transmissão , Modelos Biológicos , Número Básico de Reprodução/estatística & dados numéricos , COVID-19/terapia , Vacinas contra COVID-19/farmacologia , Simulação por Computador , Humanos , Conceitos Matemáticos , Dinâmica não Linear , Pandemias/prevenção & controle , Pandemias/estatística & dados numéricos , Saúde Pública , SARS-CoV-2 , Senegal/epidemiologia , Vacinação
4.
Front Immunol ; 12: 712274, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512635

RESUMO

At present, concerns that the recent global emergence of SARS-CoV-2 variants could compromise the current vaccines have been raised, highlighting the urgent demand for new vaccines capable of eliciting T cell-mediated immune responses, as well as B cell-mediated neutralizing antibody production. In this study, we developed a novel recombinant Mycobacterium paragordonae expressing the SARS-CoV-2 receptor-binding domain (RBD) (rMpg-RBD-7) that is capable of eliciting RBD-specific immune responses in vaccinated mice. The potential use of rMpg-RBD-7 as a vaccine for SARS-CoV-2 infections was evaluated in in vivo using mouse models of two different modules, one for single-dose vaccination and the other for two-dose vaccination. In a single-dose vaccination model, we found that rMpg-RBD-7 versus a heat-killed strain could exert an enhanced cell-mediated immune (CMI) response, as well as a humoral immune response capable of neutralizing the RBD and ACE2 interaction. In a two-dose vaccination model, rMpg-RBD-7 in a two-dose vaccination could also exert a stronger CMI and humoral immune response to neutralize SARS-CoV-2 infections in pseudoviral or live virus infection systems, compared to single dose vaccinations of rMpg-RBD or two-dose RBD protein immunization. In conclusion, our data showed that rMpg-RBD-7 can lead to an enhanced CMI response and humoral immune responses in mice vaccinated with both single- or two-dose vaccination, highlighting its feasibility as a novel vaccine candidate for SARS-CoV-2. To the best of our knowledge, this study is the first in which mycobacteria is used as a delivery system for a SARS-CoV-2 vaccine.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Mycobacterium , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Vacinas contra COVID-19/farmacologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Domínios Proteicos , SARS-CoV-2
5.
Sovrem Tekhnologii Med ; 13(1): 6-13, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513061

RESUMO

The study aims to assess the role of EU biomedical research infrastructures in the fight against the COVID-19 pandemic and to analyze their response to the challenges associated with the spread of the new pathogen. Materials and Methods: We analyzed the materials of the Seventh Framework Program for Research and Technological Development (FP7, 2007-2013) of the EU and the Eighth Framework Program "Horizon 2020" (FP8, 2014-2020), official reports of the European Strategic Forum on Research Infrastructures, expert reports, as well as documents of the European Commission, the COVID-19 Data Portal, and other relevant sources of information. Results: The analysis revealed that the mechanisms created within the united European research community provided for a flexible response to the emerging threat of COVID-19 as soon as January-May 2020. In particular, information channels were established to timely analyze the research results and coordinate the efforts in the fight against COVID-19. The biomedical infrastructures created in the EU and proved successful earlier have now been mobilized to search for ways of preventing and treating COVID-19. These mechanisms facilitated communication and data exchange between various research institutions and thus laid the ground for new achievements in this area. Conclusion: The decisions taken to combat the COVID-19 pandemic have convincingly illustrated that the EU research infrastructures, integrated into a united ecosystem, are highly adaptable and flexible, which allows to realign priorities in a short time and to create instruments that enable scientists to respond to new challenges.


Assuntos
Pesquisa Biomédica/organização & administração , COVID-19 , Antivirais/farmacologia , Bancos de Espécimes Biológicos , Vacinas contra COVID-19/farmacologia , Ensaios Clínicos como Assunto , União Europeia , Troca de Informação em Saúde , Humanos , Armazenamento e Recuperação da Informação , Cooperação Internacional , Pesquisa Médica Translacional/organização & administração
6.
Circ Heart Fail ; 14(9): e008354, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34517720

RESUMO

BACKGROUND: It is important to understand the risk for in-hospital mortality of adults hospitalized with acute coronavirus disease 2019 (COVID-19) infection with a history of heart failure (HF). METHODS: We examined patients hospitalized with COVID-19 infection from January 1, 2020 to July 22, 2020, from 88 centers across the US participating in the American Heart Association's COVID-19 Cardiovascular Disease registry. The primary exposure was history of HF and the primary outcome was in-hospital mortality. To examine the association between history of HF and in-hospital mortality, we conducted multivariable modified Poisson regression models that included sociodemographics and comorbid conditions. We also examined HF subtypes based on left ventricular ejection fraction in the prior year, when available. RESULTS: Among 8920 patients hospitalized with COVID-19, mean age was 61.4±17.5 years and 55.5% were men. History of HF was present in 979 (11%) patients. In-hospital mortality occurred in 31.6% of patients with history of HF, and 16.9% in patients without a history of HF. In a fully adjusted model, history of HF was associated with increased risk for in-hospital mortality (relative risk: 1.16 [95% CI, 1.03-1.30]). Among 335 patients with left ventricular ejection fraction, heart failure with reduced ejection fraction was significantly associated with in-hospital mortality in a fully adjusted model (heart failure with reduced ejection fraction relative risk: 1.40 [95% CI, 1.10-1.79]; heart failure with mid-range ejection fraction relative risk: 1.06 [95% CI, 0.65-1.73]; heart failure with preserved ejection fraction relative risk, 1.06 [95% CI, 0.84-1.33]). CONCLUSIONS: Risk for in-hospital mortality was substantial among adults with history of HF, in large part due to age and comorbid conditions. History of heart failure with reduced ejection fraction may confer especially elevated risk. This population thus merits prioritization for the COVID-19 vaccine.


Assuntos
Vacinas contra COVID-19/farmacologia , COVID-19/mortalidade , Insuficiência Cardíaca/mortalidade , Volume Sistólico/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/fisiopatologia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , SARS-CoV-2/patogenicidade
9.
Int J Mol Sci ; 22(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34445329

RESUMO

Melatonin is registered to treat circadian rhythm sleep-wake disorders and insomnia in patients aged 55 years and over. The essential role of the circadian sleep rhythm in the deterioration of sleep quality during COVID-19 confinement and the lack of an adverse effect of melatonin on respiratory drive indicate that melatonin has the potential to be a recommended treatment for sleep disturbances related to COVID-19. This review article describes the effects of melatonin additional to its sleep-related effects, which make this drug an attractive therapeutic option for treating patients with COVID-19. The preclinical data suggest that melatonin may inhibit COVID-19 progression. It may lower the risk of the entrance of the SARS-CoV-2 virus into cells, reduce uncontrolled hyper-inflammation and the activation of immune cells, limit the damage of tissues and multiorgan failure due to the action of free radicals, and reduce ventilator-induced lung injury and the risk of disability resulting from fibrotic changes within the lungs. Melatonin may also increase the efficacy of COVID-19 vaccination. The high safety profile of melatonin and its potential anti-SARS-CoV-2 effects make this molecule a preferable drug for treating sleep disturbances in COVID-19 patients. However, randomized clinical trials are needed to verify the clinical usefulness of melatonin in the treatment of COVID-19.


Assuntos
COVID-19/tratamento farmacológico , Melatonina/farmacologia , SARS-CoV-2/efeitos dos fármacos , COVID-19/virologia , Vacinas contra COVID-19/farmacologia , Citocinas/metabolismo , Sequestradores de Radicais Livres/metabolismo , Humanos , Melatonina/uso terapêutico , Sistema Renina-Angiotensina , Transtornos do Sono-Vigília/tratamento farmacológico
10.
Biomed Pharmacother ; 142: 112015, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34388532

RESUMO

COVID-19, an infectious disease, has emerged as one of the leading causes of death worldwide, making it one of the severe public health issues in recent decades. nCoV, the novel SARS coronavirus that causes COVID-19, has brought together scientists in the quest for possible therapeutic and preventive measures. The development of new drugs to manage COVID-19 effectively is a challenging and time-consuming process, thus encouraging extensive investigation of drug repurposing and repositioning candidates. Several medications, including remdesivir, hydroxychloroquine, chloroquine, lopinavir, favipiravir, ribavirin, ritonavir, interferons, azithromycin, capivasertib and bevacizumab, are currently under clinical trials for COVID-19. In addition, several medicinal plants with considerable antiviral activities are potential therapeutic candidates for COVID-19. Statistical data show that the pandemic is yet to slow down, and authorities are placing their hopes on vaccines. Within a short period, four types of vaccines, namely, whole virus, viral vector, protein subunit, and nucleic acid (RNA/DNA), which can confer protection against COVID-19 in different ways, were already in a clinical trial. SARS-CoV-2 variants spread is associated with antibody escape from the virus Spike epitopes, which has grave concerns for viral re-infection and even compromises the effectiveness of the vaccines. Despite these efforts, COVID-19 treatment is still solely based on clinical management through supportive care. We aim to highlight the recent trends in COVID-19, relevant statistics, and clinical findings, as well as potential therapeutics, including in-line treatment methods, preventive measures, and vaccines to combat the prevalence of COVID-19.


Assuntos
Antivirais , Vacinas contra COVID-19 , COVID-19/tratamento farmacológico , SARS-CoV-2/efeitos dos fármacos , Antivirais/classificação , Antivirais/farmacologia , COVID-19/classificação , COVID-19/complicações , COVID-19/prevenção & controle , Vacinas contra COVID-19/classificação , Vacinas contra COVID-19/farmacologia , Desenvolvimento de Medicamentos/métodos , Descoberta de Drogas/métodos , Reposicionamento de Medicamentos/métodos , Humanos
12.
Cells ; 10(8)2021 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-34440721

RESUMO

At the end of 2020, population-based vaccination programs with new generation mRNA-based vaccines began almost all over the world. The aim of the study was to evaluate the titer of anti-SARS-CoV-2 IgG antibodies against the S1 subunit of the virus's spike protein as a marker of the humoral response in 477 patients and the concentration of interferon-gamma as an indicator of cellular response in 28 individuals. In our studies, we used serological enzyme-linked immunosorbent assays. IgG was measured in weeks 2 and 3 after the first dose and 1-5 weeks after the second dose of an mRNA vaccine in seropositive and seronegative individuals as well as in symptomatic and asymptomatic convalescents. High levels of antibodies were observed in 98% of our vaccinated cohort, and the presence of protective T cells was confirmed in the blood samples of all participants. The humoral immune response is diversified and is visible as early as 2-3 weeks after the first dose of the mRNA vaccine. The level of protection increased significantly after the second dose, with the increase being much greater in pre-vaccine healthy subjects and less in convalescents. In the second and third weeks after the second dose, the concentration of IgG antibodies was the highest, and in the following weeks, it decreased gradually. Regular serological measurements on eight subjects show that antibody titers are lower four months after vaccination than before the second dose.


Assuntos
Anticorpos Antivirais/sangue , Vacinas contra COVID-19/farmacologia , Imunoglobulina G/sangue , Interferon gama/sangue , SARS-CoV-2/imunologia , Adulto , Fatores Etários , Idoso , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Polônia , Fatores Sexuais , Fatores de Tempo
13.
Biomed Pharmacother ; 142: 111953, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34343897

RESUMO

Currently, there are over 230 different COVID-19 vaccines under development around the world. At least three decades of scientific development in RNA biology, immunology, structural biology, genetic engineering, chemical modification, and nanoparticle technologies allowed the accelerated development of fully synthetic messenger RNA (mRNA)-based vaccines within less than a year since the first report of a SARS-CoV-2 infection. mRNA-based vaccines have been shown to elicit broadly protective immune responses, with the added advantage of being amenable to rapid and flexible manufacturing processes. This review recapitulates current advances in engineering the first two SARS-CoV-2-spike-encoding nucleoside-modified mRNA vaccines, highlighting the strategies followed to potentiate their effectiveness and safety, thus facilitating an agile response to the current COVID-19 pandemic.


Assuntos
Engenharia Biomédica , Vacinas contra COVID-19 , COVID-19 , Desenvolvimento de Medicamentos/métodos , Descoberta de Drogas/métodos , SARS-CoV-2 , Engenharia Biomédica/métodos , Engenharia Biomédica/tendências , COVID-19/prevenção & controle , COVID-19/virologia , Vacinas contra COVID-19/classificação , Vacinas contra COVID-19/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Humanos , Imunogenicidade da Vacina , Lipossomos/farmacologia , Nanopartículas , Nucleosídeos/farmacologia , Nucleosídeos/fisiologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Sintéticas/farmacologia
15.
Proc Natl Acad Sci U S A ; 118(29)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34193524

RESUMO

Successfully combating the COVID-19 pandemic depends on mass vaccination with suitable vaccines to achieve herd immunity. Here, we describe COVI-VAC, the only live attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine currently in clinical development. COVI-VAC was developed by recoding a segment of the viral spike protein with synonymous suboptimal codon pairs (codon-pair deoptimization), thereby introducing 283 silent (point) mutations. In addition, the furin cleavage site within the spike protein was deleted from the viral genome for added safety of the vaccine strain. Except for the furin cleavage site deletion, the COVI-VAC and parental SARS-CoV-2 amino acid sequences are identical, ensuring that all viral proteins can engage with the host immune system of vaccine recipients. COVI-VAC was temperature sensitive in vitro yet grew robustly (>107 plaque forming units/mL) at the permissive temperature. Tissue viral loads were consistently lower, lung pathology milder, and weight loss reduced in Syrian golden hamsters (Mesocricetus auratus) vaccinated intranasally with COVI-VAC compared to those inoculated with wild-type (WT) virus. COVI-VAC inoculation generated spike IgG antibody levels and plaque reduction neutralization titers similar to those in hamsters inoculated with WT virus. Upon challenge with WT virus, COVI-VAC vaccination reduced lung challenge viral titers, resulted in undetectable virus in the brain, and protected hamsters from almost all SARS-CoV-2-associated weight loss. Highly attenuated COVI-VAC is protective at a single intranasal dose in a relevant in vivo model. This, coupled with its large-scale manufacturing potential, supports its potential use in mass vaccination programs.


Assuntos
Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/farmacologia , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Animais , Anticorpos Antivirais/imunologia , COVID-19/epidemiologia , Chlorocebus aethiops , Feminino , Humanos , Masculino , Mesocricetus , Pandemias , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação , Vacinas Atenuadas/imunologia , Células Vero
16.
J Am Soc Nephrol ; 32(8): 1880-1886, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34215666

RESUMO

BACKGROUND: Although reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rare among individuals with few coronavirus disease 2019 (COVID-19) risk factors, the ability of naturally acquired immunity to prevent reinfection among patients with ESKD is not known. METHODS: This prospective study was conducted among adults with ESKD treated with in-center hemodialysis (ICHD) in the United States. Exposure was ascribed on the basis of the presence or absence of IgG against SARS-CoV-2 at baseline, and separately, a history of documented COVID-19 before study entry. Outcomes were assessed after an infection-free period, and were any SARS-CoV-2 infection (i.e., detected by protocolized PCR tests or during routine clinical surveillance), and clinically manifest COVID-19 (consisting of only the latter). RESULTS: Of 2337 consented participants who met study inclusion criteria, 9.5% were anti-SARS-CoV-2 IgG positive at baseline; 3.6% had a history of COVID-19. Over 6679 patient-months of follow-up, 263 participants had evidence of any SARS-CoV-2 infection, including 141 who had clinically manifest COVID-19. Presence of anti-SARS-CoV-2 IgG (versus its absence) at baseline was associated with lower risk of any SARS-CoV-2 infection (incidence rate ratio, 0.55; 95% confidence interval, 0.32 to 0.95) and clinically manifest COVID-19 0.21 (95% confidence interval, 0.07 to 0.67). CONCLUSION: Among patients with ESKD, naturally acquired anti-SARS-CoV-2 IgG positivity is associated with a 45% lower risk of subsequent SARS-CoV-2 infection, and a 79% lower risk of clinically manifest COVID-19. Because natural immunity is incomplete, patients with ESKD should be prioritized for SARS-CoV-2 vaccination, independent of their COVID-19 disease history.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/complicações , COVID-19/imunologia , Falência Renal Crônica/complicações , Falência Renal Crônica/imunologia , Diálise Renal , SARS-CoV-2/imunologia , Idoso , COVID-19/epidemiologia , Vacinas contra COVID-19/farmacologia , Estudos de Coortes , Feminino , Humanos , Imunidade Inata , Imunoglobulina G/sangue , Incidência , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , Reinfecção/complicações , Reinfecção/epidemiologia , Reinfecção/imunologia , Fatores de Risco , Estados Unidos/epidemiologia
17.
Virol J ; 18(1): 154, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301275

RESUMO

The COVID-19 pandemic has put healthcare infrastructures and our social and economic lives under unprecedented strain. Effective solutions are needed to end the pandemic while significantly lessening its further impact on mortality and social and economic life. Effective and widely-available vaccines have appropriately long been seen as the best way to end the pandemic. Indeed, the current availability of several effective vaccines are already making a significant progress towards achieving that goal. Nevertheless, concerns have risen due to new SARS-CoV-2 variants that harbor mutations against which current vaccines are less effective. Furthermore, some individuals are unwilling or unable to take the vaccine. As health officials across the globe scramble to vaccinate their populations to reach herd immunity, the challenges noted above indicate that COVID-19 therapeutics are still needed to work alongside the vaccines. Here we describe the impact that neutralizing antibodies have had on those with early or mild COVID-19, and what their approval for early management of COVID-19 means for other viral entry inhibitors that have a similar mechanism of action. Importantly, we also highlight studies that show that therapeutic strategies involving various viral entry inhibitors such as multivalent antibodies, recombinant ACE2 and miniproteins can be effective not only for pre-exposure prophylaxis, but also in protecting against SARS-CoV-2 antigenic drift and future zoonotic sarbecoviruses.


Assuntos
COVID-19/tratamento farmacológico , COVID-19/virologia , SARS-CoV-2/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/metabolismo , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/epidemiologia , Vacinas contra COVID-19/farmacologia , Catepsinas/metabolismo , Humanos , Mutação , Pandemias , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Serina Endopeptidases/efeitos dos fármacos , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo
18.
Curr Biol ; 31(14): R918-R929, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34314723

RESUMO

One year into the global COVID-19 pandemic, the focus of attention has shifted to the emergence and spread of SARS-CoV-2 variants of concern (VOCs). After nearly a year of the pandemic with little evolutionary change affecting human health, several variants have now been shown to have substantial detrimental effects on transmission and severity of the virus. Public health officials, medical practitioners, scientists, and the broader community have since been scrambling to understand what these variants mean for diagnosis, treatment, and the control of the pandemic through nonpharmaceutical interventions and vaccines. Here we explore the evolutionary processes that are involved in the emergence of new variants, what we can expect in terms of the future emergence of VOCs, and what we can do to minimise their impact.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/transmissão , COVID-19/virologia , SARS-CoV-2/patogenicidade , Animais , Evolução Biológica , COVID-19/mortalidade , Vacinas contra COVID-19/farmacologia , Humanos , Controle de Infecções , Mutação , SARS-CoV-2/genética , Seleção Genética
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