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1.
Arch Immunol Ther Exp (Warsz) ; 69(1): 10, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33811524

RESUMO

The review discusses a new approach to the prevention and treatment of viral infections based on the use of pine needles polyprenyl phosphate (PPP) and associated with the infringement of prenylation process-the attachment of farnesol or geranyl geraniol to the viral protein. Currently, prenylation has been detected in type 1 adenovirus, hepatitis C virus, several herpes viruses, influenza virus, HIV. However, this list is far from complete, given that prenylated proteins play an extremely important role in the activity of the virus. We assume that the interferon produced in response to PPP may suppress expression of the SREBP2 transcription factor. As a result, the mevalonic acid pathway is violated and, as a result, the formation of early polyprenols precursors (geraniol, geranyl geraniol, farnesol), which are necessary for the prenylation of viral proteins, is blocked and the formation of mature, virulent virus particles is broken. As a consequence, the maturation of viral particles is inhibited, and defective particles are formed. Polyprenol was extracted from greenery (pine, fir and spruce needles, mulberry leaves, etc.), purified by chromatography, phosphorylated and identified by HPLC and NMR. Obtained PPP was used as antiviral in some experimental models in vitro and in vivo. During numerous studies, it was found that PPP manifested versatile antiviral effects, both in vitro and in vivo. The maximum effect was observed with viruses in which the presence of prenylated proteins was established, namely influenza A virus, HIV-1, tick-borne encephalitis virus, hepatitis A and C viruses, herpes simplex viruses type 1 and 2, some coronavirus. The available data obtained both in the experimental conditions and during clinical trials allow us to regard PPPs as safe and effective medicine for prevention and treatment of viral diseases.


Assuntos
Antivirais/farmacologia , Pinus/química , Fosfatos de Poli-Isoprenil/farmacologia , Prenilação de Proteína/efeitos dos fármacos , Viroses/tratamento farmacológico , Animais , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Humanos , Interferons/metabolismo , Microscopia Eletrônica , Fosfatos de Poli-Isoprenil/uso terapêutico , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Resultado do Tratamento , Proteínas Virais/metabolismo , Vírion/efeitos dos fármacos , Vírion/ultraestrutura , Viroses/imunologia , Viroses/prevenção & controle , Replicação Viral/efeitos dos fármacos , Replicação Viral/imunologia
2.
Int J Mol Sci ; 22(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33671104

RESUMO

In recent years, there has been a growth in scientific interest in nutraceuticals, which are those nutrients in foods that have beneficial effects on health. Nutraceuticals can be extracted, used for food supplements, or added to foods. There has long been interest in the antiviral properties of nutraceuticals, which are especially topical in the context of the ongoing COVID-19 pandemic. Therefore, the purpose of this review is to evaluate the main nutraceuticals to which antiviral roles have been attributed (either by direct action on viruses or by modulating the immune system), with a focus on the pediatric population. Furthermore, the possible applications of these substances against SARS-CoV-2 will be considered.


Assuntos
Antivirais/uso terapêutico , Suplementos Nutricionais , Viroses/prevenção & controle , Criança , Humanos , Probióticos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , /efeitos dos fármacos
3.
Indian J Tuberc ; 68(1): 119-124, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33641831

RESUMO

There are worldwide urgency, efforts, and uncertainties for the discovery of a vaccine against SARS CoV2. If successful, it will take its own time till useful for the humans. Till the specific vaccine is available, there are evidences for repurposing existing other vaccines. It is observed that countries having a routine BCG vaccination programme, have shown to have lower incidence of COVID-19, suggesting some protective mechanisms of BCG against COVID-19 in such countries. In countries like India despite vast population density and other adversities, and growing numbers of COVID19 infections, the mortality rate and severity of COVID has been low in comparison to some TB non-endemic countries (like Europe and USA). In addition, there are evidences that BCG vaccination offers partial protection and survival in low-income countries where tuberculosis is prevalent. The nonspecific effects (NSEs) of immune responses induced by BCG vaccination protect against other infections seem to be due to its immunological memory eliciting lymphocytes response and trained immunity. The protective effect on other viral infection in humans are believed to be mediated by heterologous lymphocyte activation and the initiation of innate immune memory may be applicable to SARS CoV2. The BCG vaccination at birth does not have a protective effect beyond childhood against COVID-19. In adults, there might be other factors dampening the virulence and pathogenicity of COVID-19. In the TB endemic countries like India, with high population density, similar to BCG vaccination, the environmental Mycobacteria might be imparting some immune-protection from severity and deaths of COVID-19.


Assuntos
Vacina BCG/uso terapêutico , /prevenção & controle , Humanos , Imunidade Inata , Memória Imunológica , Viroses/prevenção & controle
4.
J Clin Virol ; 137: 104795, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33761423

RESUMO

BACKGROUND: Since the worldwide spread of SARS-CoV-2, different European countries reacted with temporary national lockdowns with the aim to limit the virus transmission in the population. Also Austria started a lockdown of public life in March 2020. OBJECTIVES: In this study we investigated whether the circulation of different respiratory virus infections in Austria, as assessed by the established respiratory virus surveillance system, is affected by these measures as well and may reflect the success of the lockdown in limiting respiratory virus transmission. STUDY DESIGN: Sentinel data obtained for influenza virus, respiratory syncytial virus, human metapneumovirus and rhinovirus cases were analyzed and compared between the season 2019/2020 and the five previous seasons. RESULTS: We observed a rapid and statistically significant reduction of cumulative cases for all these viruses within short time after the lockdown in March 2020, compared to previous seasons (each p < 0.001). Also, sentinel screening for SARS-CoV-2 infections was performed and a decrease of SARS-CoV-2 was seen after the lockdown. While for the seasonally occurring viruses as influenza, respiratory syncytial virus or human metapneumovirus the lockdown led to the end of the annual epidemics, a re-increase of rhinovirus infections was observed after liberalization of numerous lockdown measures. CONCLUSIONS: Our data provide evidence that occurrence of different respiratory virus infections reflect not only the efficiency of lockdown measures taken against SARS-CoV-2 but it shows also the effects of lockdown releases on the transmission of respiratory viruses.


Assuntos
/epidemiologia , Controle de Doenças Transmissíveis , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/prevenção & controle , Áustria/epidemiologia , Epidemias , Humanos , Influenza Humana/virologia , Metapneumovirus/isolamento & purificação , Orthomyxoviridae/isolamento & purificação , Vigilância em Saúde Pública , Vírus Sincicial Respiratório Humano/isolamento & purificação , Infecções Respiratórias/transmissão , Infecções Respiratórias/virologia , Estudos Retrospectivos , Rhinovirus/isolamento & purificação , Estações do Ano , Viroses/epidemiologia , Viroses/prevenção & controle , Viroses/transmissão , Viroses/virologia
6.
Sci Rep ; 11(1): 5070, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658595

RESUMO

Inactivation technology for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is certainly a critical measure to mitigate the spread of coronavirus disease 2019 (COVID-19). A deep ultraviolet light-emitting diode (DUV-LED) would be a promising candidate to inactivate SARS-CoV-2, based on the well-known antiviral effects of DUV on microorganisms and viruses. However, due to variations in the inactivation effects across different viruses, quantitative evaluations of the inactivation profile of SARS-CoV-2 by DUV-LED irradiation need to be performed. In the present study, we quantify the irradiation dose of DUV-LED necessary to inactivate SARS-CoV-2. For this purpose, we determined the culture media suitable for the irradiation of SARS-CoV-2 and optimized the irradiation apparatus using commercially available DUV-LEDs that operate at a center wavelength of 265, 280, or 300 nm. Under these conditions, we successfully analyzed the relationship between SARS-CoV-2 infectivity and the irradiation dose of the DUV-LEDs at each wavelength without irrelevant biological effects. In conclusion, total doses of 1.8 mJ/cm2 for 265 nm, 3.0 mJ/cm2 for 280 nm, and 23 mJ/cm2 for 300 nm are required to inactivate 99.9% of SARS-CoV-2. Our results provide quantitative antiviral effects of DUV irradiation on SARS-CoV-2, serving as basic knowledge of inactivation technologies against SARS-CoV-2.


Assuntos
/efeitos da radiação , Terapia Ultravioleta/métodos , Inativação de Vírus/efeitos da radiação , /epidemiologia , Humanos , Raios Ultravioleta , Viroses/prevenção & controle
7.
Medicine (Baltimore) ; 100(10): e24853, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725841

RESUMO

BACKGROUND: Rituximab is an induction immunosuppressant essential for ABO-incompatible kidney transplantation (ABOi KT). However, studies on its dosing, which differs among countries and transplant centers, are lacking. Therefore, we retrospectively investigated the effectiveness of the induction dose of rituximab against patient mortality, graft failure, and adverse events. METHODS: We included the studies referring to at least 2 of eligible induction doses (200 mg, 200-500 mg, or 500 mg) of rituximab during ABOi KT and relevant outcomes such as patient survival, graft failure, and bacterial and viral infections. We performed direct and indirect network meta-analyses using Bayesian models and ranked different rituximab doses using generation mixed treatment comparison. Publications were retrieved using CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2020 and analyzed. The GRADE of network meta-analysis approach specified 4 levels of certainty for a given result: high, moderate, low, and very low. RESULTS: Among the 4256 patients from 21 trials, glomerular filtration rate, graft loss, antibody-mediated rejection, T-cell mediated rejection, fungal infection, bacterial infection, and CMV infection did not differ among ABOi groups treated with different rituximab doses. The effect on mortality was significantly higher in rituximab 200 to 500 mg, and rituximab 500 mg groups (odds ratios [OR] 3.5, 95% CrI: 1.3-9.8, and OR 3.0, 95% CrI 1.1-9.8), but not in rituximab 20 mg group (OR 0.45, 95% CrI 0.036-2.5). The incidence of BK virus was significantly lower in the rituximab 200-mg group than in the other groups. DISCUSSION: In ABO-incompatible kidney transplantation, low-dose rituximab is more efficacious than higher doses and reduces serious infection risks. Additional randomized controlled trials might be needed to confirm these findings due to small sample size.


Assuntos
Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Imunossupressores/administração & dosagem , Transplante de Rim , Complicações Pós-Operatórias/prevenção & controle , Rituximab/administração & dosagem , Infecções Bacterianas/prevenção & controle , Teorema de Bayes , Esquema de Medicação , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Humanos , Quimioterapia de Indução , Transplante de Rim/efeitos adversos , Doadores Vivos , Micoses/prevenção & controle , Metanálise em Rede , Viroses/prevenção & controle
8.
Am J Respir Crit Care Med ; 203(9): 1112-1118, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33534659

RESUMO

Rationale: Patients with severe coronavirus disease (COVID-19) require supplemental oxygen and ventilatory support. It is unclear whether some respiratory support devices may increase the dispersion of infectious bioaerosols and thereby place healthcare workers at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Objectives: To quantitatively compare viral dispersion from invasive and noninvasive respiratory support modalities.Methods: This study used a simulated ICU room with a breathing-patient simulator exhaling nebulized bacteriophages from the lower respiratory tract with various respiratory support modalities: invasive ventilation (through an endotracheal tube with an inflated cuff connected to a mechanical ventilator), helmet ventilation with a positive end-expiratory pressure (PEEP) valve, noninvasive bilevel positive-pressure ventilation, nonrebreather face masks, high-flow nasal oxygen (HFNO), and nasal prongs.Measurements and Main Results: Invasive ventilation and helmet ventilation with a PEEP valve were associated with the lowest bacteriophage concentrations in the air, and HFNO and nasal prongs were associated with the highest concentrations. At the intubating position, bacteriophage concentrations associated with HFNO (2.66 × 104 plaque-forming units [PFU]/L of air sampled), nasal prongs (1.60 × 104 PFU/L of air sampled), nonrebreather face masks (7.87 × 102 PFU/L of air sampled), and bilevel positive airway pressure (1.91 × 102 PFU/L of air sampled) were significantly higher than those associated with invasive ventilation (P < 0.05 for each). The difference between bacteriophage concentrations associated with helmet ventilation with a PEEP valve (4.29 × 10-1 PFU/L of air sampled) and bacteriophage concentrations associated with invasive ventilation was not statistically significant.Conclusions: These findings highlight the potential differential risk of dispersing virus among respiratory support devices and the importance of appropriate infection prevention and control practices and personal protective equipment for healthcare workers when caring for patients with transmissible respiratory viral infections such as SARS-CoV-2.


Assuntos
Cuidados Críticos/métodos , DNA Viral/análise , Transmissão de Doença Infecciosa/prevenção & controle , Insuficiência Respiratória/terapia , Ventiladores Mecânicos/efeitos adversos , Viroses/virologia , Vírus/genética , Humanos , Viroses/prevenção & controle , Viroses/transmissão
9.
Euro Surveill ; 26(3)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33478622

RESUMO

When facing an emerging virus outbreak such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a quick reaction time is key to control the spread. It takes time to develop antivirals and vaccines, and implement vaccination campaigns. Therefore, preventive measures such as rapid isolation of cases and identification and early quarantine of cases' close contacts-as well as masks, physical distancing, hand hygiene, surface disinfection and air control-are crucial to reduce the risk of transmission. In this context, disinfectants and antiseptics with proven efficacy against the outbreak virus should be used. However, biocidal formulations are quite complex and may include auxiliary substances such as surfactants or emollients in addition to active substances. In order to evaluate disinfectants' efficacy objectively, meaningful efficacy data are needed. Therefore, the European Committee for Standardisation technical committee 216 'Chemical disinfectants and antiseptics' Working Group 1 (medical area) has developed standards for efficacy testing. The European tiered approach grades the virucidal efficacy in three levels, with corresponding marker test viruses. In the case of SARS-CoV-2, disinfectants with proven activity against vaccinia virus, the marker virus for the European claim 'active against enveloped viruses', should be used to ensure effective hygiene procedures to control the pandemic.


Assuntos
Anti-Infecciosos Locais/farmacologia , Anti-Infecciosos Locais/normas , Desinfetantes/farmacologia , Desinfetantes/normas , Medicina Preventiva/normas , Viroses/prevenção & controle , Guias como Assunto , Humanos , Pandemias/prevenção & controle
10.
Biochem Soc Trans ; 49(1): 281-295, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33439253

RESUMO

Although transport into the nucleus mediated by the importin (IMP) α/ß1-heterodimer is central to viral infection, small molecule inhibitors of IMPα/ß1-dependent nuclear import have only been described and shown to have antiviral activity in the last decade. Their robust antiviral activity is due to the strong reliance of many different viruses, including RNA viruses such as human immunodeficiency virus-1 (HIV-1), dengue (DENV), and Zika (ZIKV), on the IMPα/ß1-virus interface. High-throughput compound screens have identified many agents that specifically target this interface. Of these, agents targeting IMPα/ß1 directly include the FDA-approved macrocyclic lactone ivermectin, which has documented broad-spectrum activity against a whole range of viruses, including HIV-1, DENV1-4, ZIKV, West Nile virus (WNV), Venezuelan equine encephalitis virus, chikungunya, and most recently, SARS-CoV-2 (COVID-19). Ivermectin has thus far been tested in Phase III human clinical trials for DENV, while there are currently close to 80 trials in progress worldwide for SARS-CoV-2; preliminary results for randomised clinical trials (RCTs) as well as observational/retrospective studies are consistent with ivermectin affording clinical benefit. Agents that target the viral component of the IMPα/ß1-virus interface include N-(4-hydroxyphenyl) retinamide (4-HPR), which specifically targets DENV/ZIKV/WNV non-structural protein 5 (NS5). 4-HPR has been shown to be a potent inhibitor of infection by DENV1-4, including in an antibody-dependent enhanced animal challenge model, as well as ZIKV, with Phase II clinical challenge trials planned. The results from rigorous RCTs will help determine the therapeutic potential of the IMPα/ß1-virus interface as a target for antiviral development.


Assuntos
Ivermectina/farmacologia , Proteínas não Estruturais Virais/metabolismo , Viroses/prevenção & controle , Vírus/metabolismo , alfa Carioferinas/metabolismo , beta Carioferinas/metabolismo , Animais , Antivirais/farmacologia , Humanos , Ligação Proteica/efeitos dos fármacos , Viroses/metabolismo , Viroses/virologia , Vírus/patogenicidade
11.
PLoS One ; 16(1): e0244983, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33400714

RESUMO

Here we look into the spread of aerosols indoors that may potentially carry viruses. Many viruses, including the novel SARS-CoV-2, are known to spread via airborne and air-dust pathways. From the literature data and our research on the propagation of fine aerosols, we simulate herein the carryover of viral aerosols in indoor air. We demonstrate that a lot of fine droplets released from an infected person's coughing, sneezing, or talking propagate very fast and for large distances indoors, as well as bend around obstacles, lift up and down over staircases, and so on. This study suggests equations to evaluate the concentration of those droplets, depending on time and distance from the source of infection. Estimates are given for the safe distance to the source of infection, and available methods for neutralizing viral aerosols indoors are considered.


Assuntos
/transmissão , Transmissão de Doença Infecciosa/prevenção & controle , Aerossóis/análise , Microbiologia do Ar , Poluição do Ar em Ambientes Fechados/análise , /virologia , Tosse , Transmissão de Doença Infecciosa/estatística & dados numéricos , Poeira , Humanos , Modelos Teóricos , Espirro/fisiologia , Viroses/prevenção & controle
12.
Methods Mol Biol ; 2183: 575-585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32959269

RESUMO

Despite the widespread need to assess cell-based viral infectivity during vaccine development and production, as well as viral clearance monitoring and adventitious agent testing for viral safety, traditional methods, including the end-point dilution assay (TCID50) and viral plaque assay, are slow, labor-intensive, and can vary depending upon the skill and experience of the user. LumaCyte's Radiance® instrument uses Laser Force CytologyTM (LFC), a combination of advanced optics and microfluidics, to rapidly analyze the viral infectivity of cell populations in a quantitative fashion. LFC applies optical and fluidic forces to single cells in order to measure their intrinsic biophysical and biochemical properties without the use of stains, antibodies or fluorescent labels. These properties, including refractive index, change with a wide variety of biological phenomena, including viral infection, cell differentiation, activation, size, and cytoskeletal stiffness. Here, we present the experimental design and methods to use LFC data to facilitate rapid and robust infectivity measurements for a variety of applications including initial titer measurement (TCID50 replacement), in-process infectivity (e.g., bioreactor monitoring), and viral neutralization (PRNT replacement).


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Testes de Neutralização , Carga Viral , Ensaio de Placa Viral , Viroses/imunologia , Viroses/virologia , Animais , Adesão Celular , Chlorocebus aethiops , Células HEK293 , Humanos , Células Sf9 , Vacinas/imunologia , Células Vero , Viroses/prevenção & controle
16.
Salud Colect ; 16: e2897, 2020 10 17.
Artigo em Espanhol | MEDLINE | ID: mdl-33147400

RESUMO

Taking into account the latent threat of future pandemics, the objective of this study is to analyze - particularly with respect to medications - the sustainability of the health system, healthcare coverage, budgetary efficiency, and connections with the pharmaceutical patent system. In this context, the pharmaceutical patent system acts as a determining factor, given that promoting its existence stimulates the production of research, but in turn its existence stands in the way of rapid advancements, primarily due to the development of protective legislation concerning patents, which has largely accommodated the industry. Given that the pharmaceutical industry has managed to extend the duration of patents and avoid the incorporation of generics, our analysis focuses on the influence of pharmaceutical patents; this influence has led to reflection on the possibility of combining efforts by forging alliances between numerous companies and the public sector in order to face the challenges posed by new diseases caused by viruses that give rise to epidemics and pandemics.


Assuntos
Antivirais , Custos de Medicamentos , Indústria Farmacêutica/organização & administração , Política de Saúde , Acesso aos Serviços de Saúde/organização & administração , Patentes como Assunto , Viroses/tratamento farmacológico , Antivirais/economia , Antivirais/uso terapêutico , Medicamentos Genéricos , Saúde Global , Humanos , Pandemias , Avaliação de Programas e Projetos de Saúde , Viroses/economia , Viroses/epidemiologia , Viroses/prevenção & controle
18.
mSphere ; 5(5)2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087516

RESUMO

Supply shortages of N95 respirators during the coronavirus disease 2019 (COVID-19) pandemic have motivated institutions to develop feasible and effective N95 respirator reuse strategies. In particular, heat decontamination is a treatment method that scales well and can be implemented in settings with variable or limited resources. Prior studies using multiple inactivation methods, however, have often focused on a single virus under narrowly defined conditions, making it difficult to develop guiding principles for inactivating emerging or difficult-to-culture viruses. We systematically explored how temperature, humidity, and virus deposition solutions impact the inactivation of viruses deposited and dried on N95 respirator coupons. We exposed four virus surrogates across a range of structures and phylogenies, including two bacteriophages (MS2 and phi6), a mouse coronavirus (murine hepatitis virus [MHV]), and a recombinant human influenza A virus subtype H3N2 (IAV), to heat treatment for 30 min in multiple deposition solutions across several temperatures and relative humidities (RHs). We observed that elevated RH was essential for effective heat inactivation of all four viruses tested. For heat treatments between 72°C and 82°C, RHs greater than 50% resulted in a >6-log10 inactivation of bacteriophages, and RHs greater than 25% resulted in a >3.5-log10 inactivation of MHV and IAV. Furthermore, deposition of viruses in host cell culture media greatly enhanced virus inactivation by heat and humidity compared to other deposition solutions, such as phosphate-buffered saline, phosphate-buffered saline with bovine serum albumin, and human saliva. Past and future heat treatment methods must therefore explicitly account for deposition solutions as a factor that will strongly influence observed virus inactivation rates. Overall, our data set can inform the design and validation of effective heat-based decontamination strategies for N95 respirators and other porous surfaces, especially for emerging viruses that may be of immediate and future public health concern.IMPORTANCE Shortages of personal protective equipment, including N95 respirators, during the coronavirus (CoV) disease 2019 (COVID-19) pandemic have highlighted the need to develop effective decontamination strategies for their reuse. This is particularly important in health care settings for reducing exposure to respiratory viruses, like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. Although several treatment methods are available, a widely accessible strategy will be necessary to combat shortages on a global scale. We demonstrate that the combination of heat and humidity inactivates a range of RNA viruses, including both viral pathogens and common viral pathogen surrogates, after deposition on N95 respirators and achieves the necessary virus inactivation detailed by the U.S. Food and Drug Administration guidelines to validate N95 respirator decontamination technologies. We further demonstrate that depositing viruses onto surfaces when suspended in culture media can greatly enhance observed inactivation, adding caution to how heat and humidity treatment methods are validated.


Assuntos
Descontaminação/métodos , Temperatura Alta , Umidade , Ventiladores Mecânicos , Viroses/prevenção & controle , Inativação de Vírus , Fenômenos Fisiológicos Virais , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Solução Salina , Saliva , Soroalbumina Bovina
19.
Biochem Soc Trans ; 48(5): 2173-2184, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33119046

RESUMO

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


Assuntos
Coronavirus/fisiologia , Retículo Endoplasmático/metabolismo , Flavivirus/fisiologia , Interações Hospedeiro-Patógeno , Polyomavirus/fisiologia , Humanos , Chaperonas Moleculares/metabolismo , Viroses/metabolismo , Viroses/prevenção & controle , Internalização do Vírus , Replicação Viral
20.
Cochrane Database Syst Rev ; 10: CD013686, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047816

RESUMO

BACKGROUND: Many dental procedures produce aerosols (droplets, droplet nuclei and splatter) that harbour various pathogenic micro-organisms and may pose a risk for the spread of infections between dentist and patient. The COVID-19 pandemic has led to greater concern about this risk. OBJECTIVES: To assess the effectiveness of methods used during dental treatment procedures to minimize aerosol production and reduce or neutralize contamination in aerosols. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases on 17 September 2020: Cochrane Oral Health's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (in the Cochrane Library, 2020, Issue 8), MEDLINE Ovid (from 1946); Embase Ovid (from 1980); the WHO COVID-19 Global literature on coronavirus disease; the US National Institutes of Health Trials Registry (ClinicalTrials.gov); and the Cochrane COVID-19 Study Register. We placed no restrictions on the language or date of publication. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on aerosol-generating procedures (AGPs) performed by dental healthcare providers that evaluated methods to reduce contaminated aerosols in dental clinics (excluding preprocedural mouthrinses). The primary outcomes were incidence of infection in dental staff or patients, and reduction in volume and level of contaminated aerosols in the operative environment. The secondary outcomes were cost, accessibility and feasibility. DATA COLLECTION AND ANALYSIS: Two review authors screened search results, extracted data from the included studies, assessed the risk of bias in the studies, and judged the certainty of the available evidence. We used mean differences (MDs) and 95% confidence intervals (CIs) as the effect estimate for continuous outcomes, and random-effects meta-analysis to combine data. We assessed heterogeneity. MAIN RESULTS: We included 16 studies with 425 participants aged 5 to 69 years. Eight studies had high risk of bias; eight had unclear risk of bias. No studies measured infection. All studies measured bacterial contamination using the surrogate outcome of colony-forming units (CFU). Two studies measured contamination per volume of air sampled at different distances from the patient's mouth, and 14 studies sampled particles on agar plates at specific distances from the patient's mouth. The results presented below should be interpreted with caution as the evidence is very low certainty due to heterogeneity, risk of bias, small sample sizes and wide confidence intervals. Moreover, we do not know the 'minimal clinically important difference' in CFU. High-volume evacuator Use of a high-volume evacuator (HVE) may reduce bacterial contamination in aerosols less than one foot (~ 30 cm) from a patient's mouth (MD -47.41, 95% CI -92.76 to -2.06; 3 RCTs, 122 participants (two studies had split-mouth design); very high heterogeneity I² = 95%), but not at longer distances (MD -1.00, -2.56 to 0.56; 1 RCT, 80 participants). One split-mouth RCT (six participants) found that HVE may not be more effective than conventional dental suction (saliva ejector or low-volume evacuator) at 40 cm (MD CFU -2.30, 95% CI -5.32 to 0.72) or 150 cm (MD -2.20, 95% CI -14.01 to 9.61). Dental isolation combination system One RCT (50 participants) found that there may be no difference in CFU between a combination system (Isolite) and a saliva ejector (low-volume evacuator) during AGPs (MD -0.31, 95% CI -0.82 to 0.20) or after AGPs (MD -0.35, -0.99 to 0.29). However, an 'n of 1' design study showed that the combination system may reduce CFU compared with rubber dam plus HVE (MD -125.20, 95% CI -174.02 to -76.38) or HVE (MD -109.30, 95% CI -153.01 to -65.59). Rubber dam One split-mouth RCT (10 participants) receiving dental treatment, found that there may be a reduction in CFU with rubber dam at one-metre (MD -16.20, 95% CI -19.36 to -13.04) and two-metre distance (MD -11.70, 95% CI -15.82 to -7.58). One RCT of 47 dental students found use of rubber dam may make no difference in CFU at the forehead (MD 0.98, 95% CI -0.73 to 2.70) and occipital region of the operator (MD 0.77, 95% CI -0.46 to 2.00). One split-mouth RCT (21 participants) found that rubber dam plus HVE may reduce CFU more than cotton roll plus HVE on the patient's chest (MD -251.00, 95% CI -267.95 to -234.05) and dental unit light (MD -12.70, 95% CI -12.85 to -12.55). Air cleaning systems One split-mouth CCT (two participants) used a local stand-alone air cleaning system (ACS), which may reduce aerosol contamination during cavity preparation (MD -66.70 CFU, 95% CI -120.15 to -13.25 per cubic metre) or ultrasonic scaling (MD -32.40, 95% CI - 51.55 to -13.25). Another CCT (50 participants) found that laminar flow in the dental clinic combined with a HEPA filter may reduce contamination approximately 76 cm from the floor (MD -483.56 CFU, 95% CI -550.02 to -417.10 per cubic feet per minute per patient) and 20 cm to 30 cm from the patient's mouth (MD -319.14 CFU, 95% CI - 385.60 to -252.68). Disinfectants ‒ antimicrobial coolants Two RCTs evaluated use of antimicrobial coolants during ultrasonic scaling. Compared with distilled water, coolant containing chlorhexidine (CHX), cinnamon extract coolant or povidone iodine may reduce CFU: CHX (MD -124.00, 95% CI -135.78 to -112.22; 20 participants), povidone iodine (MD -656.45, 95% CI -672.74 to -640.16; 40 participants), cinnamon (MD -644.55, 95% CI -668.70 to -620.40; 40 participants). CHX coolant may reduce CFU more than povidone iodine (MD -59.30, 95% CI -64.16 to -54.44; 20 participants), but not more than cinnamon extract (MD -11.90, 95% CI -35.88 to 12.08; 40 participants). AUTHORS' CONCLUSIONS: We found no studies that evaluated disease transmission via aerosols in a dental setting; and no evidence about viral contamination in aerosols. All of the included studies measured bacterial contamination using colony-forming units. There appeared to be some benefit from the interventions evaluated but the available evidence is very low certainty so we are unable to draw reliable conclusions. We did not find any studies on methods such as ventilation, ionization, ozonisation, UV light and fogging. Studies are needed that measure contamination in aerosols, size distribution of aerosols and infection transmission risk for respiratory diseases such as COVID-19 in dental patients and staff.


Assuntos
Microbiologia do Ar , Infecções Bacterianas/prevenção & controle , Controle de Infecções Dentárias/métodos , Doenças Profissionais/prevenção & controle , Viroses/prevenção & controle , Adolescente , Adulto , Aerossóis , Idoso , Filtros de Ar , Criança , Pré-Escolar , Contagem de Colônia Microbiana/métodos , Odontologia , Desinfetantes , Humanos , Controle de Infecções Dentárias/economia , Controle de Infecções Dentárias/instrumentação , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Diques de Borracha , Sucção , Adulto Jovem
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