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1.
Obes Sci Pract ; 10(1): e724, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38263985

RESUMO

Objective: There is substantial inter-individual variability in response to weight loss interventions and emerging evidence suggests that weight loss during the early weeks of an intervention may be predictive of longer-term weight loss. This secondary analysis of data from a commercial program therefore examined 1) the associations between early weight loss (i.e., week 4) with final visit weight loss and duration on the program, and 2) other predictors of lower weight loss at final visit. Methods: Client charts of adults with overweight or obesity (N = 748) were analyzed. Clients were stratified into categories of weight loss at the week 4 (< and ≥2%, 3% and 4%) and final visits (< and ≥5% and 10%). Multivariate logistic regression was used to assess predictors of <5% and <10% final visit weight loss. Results: The odds ratios for losing <5% or <10% of weight at the final visit were higher (49.0 (95% CI: 13.84, 173.63) and 20.1 (95% CI: 6.96, 58.06)) for clients who lost <2% or <3% compared to those who lost ≥2% or ≥3% at week 4. Other predictors of not losing a clinically relevant amount of weight included female sex, use of higher calorie meal plans and shorter time in the program, among others. Those who lost ≥2% at week 4 also had a significantly greater percent program completion (109.2 ± 75.2% vs. 82.3 ± 82.4, p < 0.01) compared with those who did not meet the 2% threshold. Conclusions: Lower 4-week weight loss was identified as a strong predictor of not losing a clinically relevant amount of weight. These results may be useful for the early identification of individuals who can be targeted for additional counseling and support to aid in attaining weight loss goals.

2.
Access Microbiol ; 5(9)2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841099

RESUMO

The SARS-CoV-2 pandemic demonstrated the importance of human coronaviruses and the need to develop materials to prevent the spread of emergent respiratory viruses. Coating of surfaces with antiviral materials is a major interest in controlling spread of viruses, especially in high-risk or high-traffic areas. A number of different coatings for surfaces have been proposed, each with their own advantages and disadvantages. Here we show that simple salt coating on a range of surfaces, including a novel biomass aerogel can reduce the infectivity of SARS-CoV-2 placed onto the surface. This suggests that a simple to apply coating could be applied to a range of materials and have an antiviral effect against SARS-CoV-2, as well as other potential emerging viruses.

3.
Nat Commun ; 14(1): 3322, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37369644

RESUMO

There has been limited characterisation of bat-borne coronaviruses in Europe. Here, we screened for coronaviruses in 48 faecal samples from 16 of the 17 bat species breeding in the UK, collected through a bat rehabilitation and conservationist network. We recovered nine complete genomes, including two novel coronavirus species, across six bat species: four alphacoronaviruses, a MERS-related betacoronavirus, and four closely related sarbecoviruses. We demonstrate that at least one of these sarbecoviruses can bind and use the human ACE2 receptor for infecting human cells, albeit suboptimally. Additionally, the spike proteins of these sarbecoviruses possess an R-A-K-Q motif, which lies only one nucleotide mutation away from a furin cleavage site (FCS) that enhances infectivity in other coronaviruses, including SARS-CoV-2. However, mutating this motif to an FCS does not enable spike cleavage. Overall, while UK sarbecoviruses would require further molecular adaptations to infect humans, their zoonotic risk warrants closer surveillance.


Assuntos
COVID-19 , Quirópteros , Animais , Humanos , COVID-19/genética , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Genômica , Reino Unido , Filogenia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo
4.
Build Environ ; 240: 110422, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37251109

RESUMO

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2, the virus that causes the coronavirus disease (COVID)-19, is primarily transmitted through respiratory droplets which linger in enclosed spaces, often exacerbated by HVAC systems. Although research to improve HVAC handling of SARS-CoV-2 is progressing, currently installed HVAC systems cause problems because they recirculate air and use ineffective filters against virus. This paper details the process of developing a novel method of eliminating air pollutants and suspended pathogens in enclosed spaces using Photocatalytic Oxidation (PCO) technology. It has been previously employed to remove organic contaminants and compounds from air streams using the irradiation of titanium dioxide (TiO2) surfaces with ultraviolet (UV) lights causing the disintegration of organic compounds by reactions with oxygen (O) and hydroxyl radicals (OH). The outcome was two functional prototypes that demonstrate the operation of PCO-based air purification principle. These prototypes comprise a novel TiO2 coated fibre mop system, which provide very large surface area for UV irradiation. Four commercially accessible materials were used for the construction of the mop: Tampico, Brass, Coco, and Natural synthetic. Two types of UV lights were used: 365 nm (UVA) and 270 nm (UVC). A series of tests were conducted that proved the prototype's functionality and its efficiency in lowering volatile organic compounds (VOCs) and formaldehyde (HCHO). The results shown that a MopFan with rotary mop constructed with Coco fibres and utilising UVC light achieves the best VOC and HCHO purification performance. Within 2 h, this combination lowered HCHO by 50% and VOCs by 23% approximately.

5.
Nurs Outlook ; 71(3): 101950, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36924597

RESUMO

BACKGROUND: In the US, sexual and gender minority (SGM) individuals continue to experience health inequities, and nursing curricula content and nursing faculty with SGM health expertise in the US remain limited. Addressing health disparities begins with the preparation of future nurses-US nursing faculty must be supported to meet these growing needs. PURPOSE: To describe, appraise, and synthesize research from 2000-2020 on US nursing faculty knowledge, awareness, inclusion, and perceived importance of SGM health content. METHODS: Following PRISMA 2020 guidelines, we registered a systematic review and appraisal protocol in PROSPERO, and then executed the protocol and synthesized the literature. DISCUSSION: We found an empirical evidence base surrounding US nursing faculty and SGM health much more limited than expected. Only four cross-sectional, descriptive empirical articles fit the a priori inclusion criteria. The studies were of moderate quality at best and often relied on unvalidated or older measures. In general, the studies focused on examining characteristics of nursing programs, faculty comfort with content, faculty perceptions of content importance, and hours dedicated to content. CONCLUSION: Since the close of the review, new commentaries and editorials expanding the call for change in the US were published-the time for commentary has passed. It remains unclear whether US nursing faculty are adequately prepared to educate future nurses about SGM health issues-and an unprepared healthcare workforce is yet another barrier to SGM health equity. The evidence base supporting US nursing faculty development desperately needs more studies using rigorous methodologies.


Assuntos
Docentes de Enfermagem , Minorias Sexuais e de Gênero , Humanos , Estudos Transversais , Identidade de Gênero , Currículo
6.
Nurs Outlook ; 71(2): 101907, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36623984

RESUMO

BACKGROUND: Lesbian, gay, bisexual, transgender, and queer plus (LGBTQ) people experience discrimination and health disparities compared to heterosexual cisgender people. Clinicians report discomfort and insufficient preparation for providing care to LGBTQ people and nursing has been slow to integrate LGBTQ health into curricula. PURPOSE: Conduct a systematic review to examine and critically appraise peer-reviewed literature on nursing student knowledge, skills, and attitudes (KSAs) regarding LGBTQ health and the development/evaluation of LGBTQ health content in nursing curricula. METHODS: A systematic review was conducted (N = 1275 articles from PubMed, LGBT Health, CINAHL, ERIC, and Health Source-Nursing/Academic Edition). FINDINGS: Twenty articles met inclusion criteria. Twelve studies described curricular interventions; however, there were few validated tools to evaluate content coverage or KSAs. Four themes emerged specific to LGBTQ health content inclusion. DISCUSSION: While an emerging science of LGBTQ nursing education has been identified, more work is needed to build and evaluate a comprehensive curricular approach for full programmatic integration of LGBTQ health. CONCLUSION: As nursing programs build LGBTQ content into nursing curricula, care must be taken to integrate this content fully with the depth of curricular content in population health, social determinants of health, social justice, intersectionality, cultural competence, and political advocacy. TWEETABLE ABSTRACT: Greater integration of LGBTQ health content into nursing education should be a priority for nursing education.


Assuntos
Educação em Enfermagem , Minorias Sexuais e de Gênero , Estudantes de Enfermagem , Feminino , Humanos , Comportamento Sexual , Educação de Pós-Graduação
7.
Am J Respir Crit Care Med ; 207(6): 693-703, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36457159

RESUMO

Rationale: Shared symptoms and genetic architecture between coronavirus disease (COVID-19) and lung fibrosis suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to progressive lung damage. Objectives: The UK Interstitial Lung Disease Consortium (UKILD) post-COVID-19 study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 on the basis of risk strata. Methods: The PHOSP-COVID-19 (Post-Hospitalization COVID-19) study was used to capture routine and research follow-up within 240 days from discharge. Thoracic computed tomography linked by PHOSP-COVID-19 identifiers was scored for the percentage of residual lung abnormalities (ground-glass opacities and reticulations). Risk factors in linked computed tomography were estimated with Bayesian binomial regression, and risk strata were generated. Numbers within strata were used to estimate posthospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol-driven research follow-up. Measurements and Main Results: The interim cohort comprised 3,700 people. Of 209 subjects with linked computed tomography (median, 119 d; interquartile range, 83-155), 166 people (79.4%) had more than 10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (risk ratio [RR], 1.21; 95% credible interval [CrI], 1.05-1.40), percent predicted DlCO less than 80% (RR, 1.25; 95% CrI, 1.00-1.56), and severe admission requiring ventilation support (RR, 1.27; 95% CrI, 1.07-1.55). In the remaining 3,491 people, moderate to very high risk of residual lung abnormalities was classified at 7.8%, and posthospitalization prevalence was estimated at 8.5% (95% CrI, 7.6-9.5), rising to 11.7% (95% CrI, 10.3-13.1) in the sensitivity analysis. Conclusions: Residual lung abnormalities were estimated in up to 11% of people discharged after COVID-19-related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications.


Assuntos
COVID-19 , Doenças Pulmonares Intersticiais , Humanos , SARS-CoV-2 , COVID-19/epidemiologia , Teorema de Bayes , Pulmão/diagnóstico por imagem , Hospitalização
8.
Eur Geriatr Med ; 13(6): 1343-1355, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36385690

RESUMO

PURPOSE: Infections cause considerable care home morbidity and mortality. Nitric oxide (NO) has broad-spectrum anti-viral, bacterial and yeast activity in vitro. We assessed the feasibility of supplementing dietary nitrate (NO substrate) intake in care home residents. METHODS: We performed a cluster-randomised placebo-controlled trial in UK residential and nursing care home residents and compared nitrate containing (400 mg) versus free (0 mg daily) beetroot juice given for 60 days. Outcomes comprised feasibility of recruitment, adherence, salivary and urinary nitrate, and ordinal infection/clinical events. RESULTS: Of 30 targeted care homes in late 2020, 16 expressed interest and only 6 participated. 49 residents were recruited (median 8 [interquartile range 7-12] per home), mean (standard deviation) age 82 (8) years, with proxy consent 41 (84%), advance directive for hospital non-admission 8 (16%) and ≥ 1 doses of COVID-19 vaccine 37 (82%). Background dietary nitrate was < 30% of acceptable daily intake. 34 (76%) residents received > 50% of juice. Residents randomised to nitrate vs placebo had higher urinary nitrate levels, median 50 [18-175] v 18 [10-50] mg/L, difference 25 [0-90]. Data paucity precluded clinical between-group comparisons; the outcome distribution was as follows: no infection 32 (67%), uncomplicated infection 0, infection requiring healthcare support 11 (23%), all-cause hospitalisation 5 (10%), all-cause mortality 0. Urinary tract infections were most common. CONCLUSIONS: Recruiting UK care homes during the COVID-19 pandemic was partially successful. Supplemented dietary nitrate was tolerated and elevated urinary nitrate. Together, infections, hospitalisations and deaths occurred in 33% of residents over 60 days. A larger trial is now required. TRIAL REGISTRATION: ISRCTN51124684. Application date 7/12/2020; assignment date 13/1/2021.


Assuntos
Beta vulgaris , COVID-19 , Humanos , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Nitratos/uso terapêutico , Pandemias , Estudos de Viabilidade , Vacinas contra COVID-19 , Suplementos Nutricionais , Óxidos de Nitrogênio
9.
Sci Rep ; 12(1): 16654, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36198720

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the causative agent of coronavirus disease 2019 (COVID-19)-has caused a global public health emergency. Personal protective equipment (PPE) is the primary defence against viral exposure in healthcare and community settings. However, the surfaces of PPE materials may trap virus for contact transmission or through laden aerosols generated during removal of PPE, through cleaning or during movement. In this study, the relative efficacy of current PPE materials in terms of virion adsorption to materials and their antiviral potency, has been evaluated on a wide range of PPE for the first time, including four polymer glove types, two types of scrubs, apron material, a mask, visor and a selection of other commercial polymers and products. Although differences in virion adsorption to the test materials were observed, none of the existing polymer-based PPE resulted in more than tenfold reduction in the SARS-CoV-2 titre within either 10 min or 30 min contact period. The wettability and surface chemistry of the test materials were analysed to investigate any correlations with their surface physicochemical properties. While no correlation was found between wettability and viral retention under air flow challenge, one secondary ion of m/z 101.03 (+) and three secondary ions of m/z 31.98 (-), 196.93 (-) and 394.33 (+) in ToF-SIMS data of the test materials showed positive and negative correlations with the viral retention, respectively, which was identified by PLS regression model, suggesting that the surface chemistry plays a role in determining the extent of virion adsorption. Our findings outline the material aspects that influence the efficacy of current PPE against SARS-CoV-2 transmission and give suggestions on the development of novel simple polymer-based PPE for better infection protection.


Assuntos
COVID-19 , Equipamento de Proteção Individual , Antivirais , COVID-19/prevenção & controle , Pessoal de Saúde , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Polímeros , Aerossóis e Gotículas Respiratórios , SARS-CoV-2
10.
Nat Commun ; 13(1): 6468, 2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36309518

RESUMO

Twisted double bilayer graphene (tDBG) comprises two Bernal-stacked bilayer graphene sheets with a twist between them. Gate voltages applied to top and back gates of a tDBG device tune both the flatness and topology of the electronic bands, enabling an unusual level of experimental control. Metallic states with broken spin and valley symmetries have been observed in tDBG devices with twist angles in the range 1.2-1.3°, but the topologies and order parameters of these states have remained unclear. We report the observation of an anomalous Hall effect in the correlated metal state of tDBG, with hysteresis loops spanning hundreds of mT in out-of-plane magnetic field (B⊥) that demonstrate spontaneously broken time-reversal symmetry. The B⊥ hysteresis persists for in-plane fields up to several Tesla, suggesting valley (orbital) ferromagnetism. At the same time, the resistivity is strongly affected by even mT-scale values of in-plane magnetic field, pointing to spin-valley coupling or to a direct orbital coupling between in-plane field and the valley degree of freedom.

11.
Conserv Sci Pract ; 4(7): e12707, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35935171

RESUMO

Several studies have suggested SARS-CoV-2 originated from a viral ancestor in bats, but whether transmission occurred directly or via an intermediary host to humans remains unknown. Concerns of spillover of SARS-CoV-2 into wild bat populations are hindering bat rehabilitation and conservation efforts in the United Kingdom and elsewhere. Current protocols state that animals cared for by individuals who have tested positive for SARS-CoV-2 cannot be released into the wild and must be isolated to reduce the risk of transmission to wild populations. Here, we propose a reverse transcription-quantitative polymerase chain reaction (RT-qPCR)-based protocol for detection of SARS-CoV-2 in bats, using fecal sampling. Bats from the United Kingdom were tested following suspected exposure to SARS-CoV-2 and tested negative for the virus. With current UK and international legislation, the identification of SARS-CoV-2 infection in wild animals is becoming increasingly important, and protocols such as the one developed here will help improve understanding and mitigation of SARS-CoV-2 in the future.

12.
Nurs Outlook ; 70(3): 513-524, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35430056

RESUMO

BACKGROUND: Lesbian, gay, bisexual, transgender and queer (LGBTQ) people, also commonly referred to as sexual and gender minorities (SGMs), live in every part of the United States and encompass all races and/or ethnicities, religions, and social classes. Major reports from various sources document higher rates of health issues (e.g., substance abuse, depression, suicidality, cardiovascular disease) among SGMs than heterosexuals. Chronic stress related to marginalization and discrimination is a key contributor to these disparities. The nursing profession has paid relatively little attention to SGM health issues. PURPOSE AND METHODS: To address these gaps, the first National Nursing LGBTQ Health Summit brought together nursing deans, leaders of national nursing organizations, and other participants from across the United States. FINDINGS: Participants agreed that increasing SGM-specific content in nursing curricula, practice guidelines, faculty development, and research is necessary to improve the health of SGM people. DISCUSSION: The Summit ended with a call to action for the nursing profession to prioritize SGM health through innovations in education, research, and practice.


Assuntos
Minorias Sexuais e de Gênero , Pessoas Transgênero , Currículo , Feminino , Identidade de Gênero , Humanos , Comportamento Sexual , Estados Unidos
13.
Virulence ; 12(1): 2946-2956, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34793280

RESUMO

The struggle to control the COVID-19 pandemic is made challenging by the emergence of virulent SARS-CoV-2 variants. To gain insight into their replication dynamics, emergent Alpha (A), Beta (B) and Delta (D) SARS-CoV-2 variants were assessed for their infection performance in single variant- and co-infections. The effectiveness of thapsigargin (TG), a recently discovered broad-spectrum antiviral, against these variants was also examined. Of the 3 viruses, the D variant exhibited the highest replication rate and was most able to spread to in-contact cells; its replication rate at 24 h post-infection (hpi) based on progeny viral RNA production was over 4 times that of variant A and 9 times more than the B variant. In co-infections, the D variant boosted the replication of its co-infected partners at the expense of its own initial performance. Furthermore, co-infection with AD or AB combination conferred replication synergy where total progeny (RNA) output was greater than the sum of corresponding single-variant infections. All variants were highly sensitive to TG inhibition. A single pre-infection priming dose of TG effectively blocked all single-variant infections and every combination (AB, AD, BD variants) of co-infection at greater than 95% (relative to controls) at 72 hpi. Likewise, TG was effective in inhibiting each variant in active preexisting infection. In conclusion, against the current backdrop of the dominant D variant that could be further complicated by co-infection synergy with new variants, the growing list of viruses susceptible to TG, a promising host-centric antiviral, now includes a spectrum of contemporary SARS-CoV-2 viruses.


Assuntos
Tratamento Farmacológico da COVID-19 , Coinfecção , SARS-CoV-2 , Tapsigargina , Antivirais/farmacologia , Antivirais/uso terapêutico , Humanos , Pandemias , SARS-CoV-2/efeitos dos fármacos , Tapsigargina/farmacologia , Tapsigargina/uso terapêutico
14.
Molecules ; 26(3)2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33498976

RESUMO

Molecular magnets attached to carbon nanotubes (CNT) are being studied as potential candidates for developing spintronic and quantum technologies. However, the functionalization routes used to develop these hybrid systems can drastically affect their respective physiochemical properties. Due to the complexity of this systems, little work has been directed at establishing the correlation between the degree of functionalization and the magnetic character. Here, we demonstrate the chemical functionalization degree associated with molecular magnet loading can be utilized for controlled tuning the magnetic properties of a CNT-lanthanide hybrid complex. CNT functionalization degree was evaluated by interpreting minor Raman phonon modes in relation to the controlled reaction conditions. These findings were exploited in attaching a rare-earth-based molecular magnet (Gd-DTPA) to the CNTs. Inductively coupled plasma mass spectrometry, time-of-flight secondary ion mass spectrometry and super conducting quantum interference device (SQUID) measurements were used to elucidate the variation of magnetic character across the samples. This controlled Gd-DTPA loading on the CNT surface has led to a significant change in the nanotube intrinsic diamagnetism, showing antiferromagnetic coupling with increase in the Weiss temperature with respect to increased loading. This indicates that synthesis of a highly correlated spin system for developing novel spintronic technologies can be realized through a carbon-based hybrid material.


Assuntos
Elementos da Série dos Lantanídeos/química , Imãs/química , Nanotubos de Carbono/química , Gadolínio DTPA/química , Fenômenos Magnéticos , Microscopia Eletrônica de Transmissão , Nanotubos de Carbono/ultraestrutura , Espectrometria de Massa de Íon Secundário , Análise Espectral Raman
15.
F1000Res ; 10: 536, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35685687

RESUMO

Although the antimicrobial potential of nitric oxide (NO) is widely published, it is little used clinically. NO is a key signalling molecule modulating vascular, neuronal, inflammatory and immune responses. Endogenous antimicrobial activity is largely mediated by high local NO concentrations produced by cellular inducible nitric oxide synthase, and by derivative reactive nitrogen oxide species including peroxynitrite and S-nitrosothiols. NO may be taken as dietary substrate (inorganic nitrate, L-arginine), and therapeutically as gaseous NO, and transdermal, sublingual, oral, intranasal and intravenous nitrite or nitrate. Numerous preclinical studies have demonstrated that NO has generic static and cidal activities against viruses (including ß-coronaviruses such as SARS-CoV-2), bacteria, protozoa and fungi/yeasts  in vitro. Therapeutic effects have been seen in animal models  in vivo, and phase II trials have demonstrated that NO donors can reduce microbial infection. Nevertheless, excess NO, as occurs in septic shock, is associated with increased morbidity and mortality. In view of the dose-dependent positive and negative effects of NO, safety and efficacy trials of NO and its donors are needed for assessing their role in the prevention and treatment of infections. Trials should test dietary inorganic nitrate for pre- or post-exposure prophylaxis and gaseous NO or oral, topical or intravenous nitrite and nitrate for treatment of mild-to-severe infections, including due to SARS-CoV-2 (COVID-19). This review summarises the evidence base from  in vitro, in vivo and early phase clinical studies of NO activity in viral, bacterial, protozoal and fungal infections.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Micoses , Animais , Bactérias , COVID-19/prevenção & controle , Micoses/tratamento farmacológico , Micoses/prevenção & controle , Nitratos , Óxido Nítrico , Nitritos , SARS-CoV-2
16.
J Virol ; 94(21)2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-32817221

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China at the end of 2019 and has rapidly caused a pandemic, with over 20 million recorded COVID-19 cases in August 2020 (https://covid19.who.int/). There are no FDA-approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments for COVID-19 are limited to supportive therapies and off-label use of FDA-approved drugs. Rapid development and human testing of potential antivirals is urgently needed. Numerous drugs are already approved for human use, and subsequently, there is a good understanding of their safety profiles and potential side effects, making them easier to fast-track to clinical studies in COVID-19 patients. Here, we present data on the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). We found that 17 of these inhibit SARS-CoV-2 at non-cytotoxic concentrations. We directly followed up seven of these to demonstrate that all are capable of inhibiting infectious SARS-CoV-2 production. Moreover, we evaluated two of these, chloroquine and chlorpromazine, in vivo using a mouse-adapted SARS-CoV model and found that both drugs protect mice from clinical disease.IMPORTANCE There are no FDA-approved antivirals for any coronavirus, including SARS-CoV-2. Numerous drugs are already approved for human use that may have antiviral activity and therefore could potentially be rapidly repurposed as antivirals. Here, we present data assessing the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV in vitro We found that 17 of these inhibit SARS-CoV-2, suggesting that they may have pan-anti-coronaviral activity. We directly followed up seven of these and found that they all inhibit infectious-SARS-CoV-2 production. Moreover, we evaluated chloroquine and chlorpromazine in vivo using mouse-adapted SARS-CoV. We found that neither drug inhibited viral replication in the lungs, but both protected against clinical disease.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Células A549 , Animais , COVID-19 , Cloroquina/farmacologia , Clorpromazina/farmacologia , Aprovação de Drogas , Avaliação Pré-Clínica de Medicamentos , Humanos , Pandemias , SARS-CoV-2 , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration , Replicação Viral/efeitos dos fármacos , Tratamento Farmacológico da COVID-19
17.
Methods Mol Biol ; 2203: 223-229, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833215

RESUMO

All viruses have to overcome the innate immune response in order to establish infection. Methods have been developed to assay if, and how, viruses overcome these responses, and many can be directly applied to coronaviruses. Here, in vitro methods to determine how coronaviruses overcome this response are described.


Assuntos
Coronavirus/crescimento & desenvolvimento , Coronavirus/metabolismo , Cultura de Vírus/métodos , Animais , Linhagem Celular , Coronavirus/patogenicidade , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata/imunologia , Interferons , Coronavírus da Síndrome Respiratória do Oriente Médio/crescimento & desenvolvimento , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , RNA Viral , Proteínas não Estruturais Virais , Replicação Viral
18.
JCI Insight ; 4(20)2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31550243

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 in Saudi Arabia and has caused over 2400 cases and more than 800 deaths. Epidemiological studies identified diabetes as the primary comorbidity associated with severe or lethal MERS-CoV infection. Understanding how diabetes affects MERS is important because of the global burden of diabetes and pandemic potential of MERS-CoV. We used a model in which mice were made susceptible to MERS-CoV by expressing human DPP4, and type 2 diabetes was induced by administering a high-fat diet. Upon infection with MERS-CoV, diabetic mice had a prolonged phase of severe disease and delayed recovery that was independent of virus titers. Histological analysis revealed that diabetic mice had delayed inflammation, which was then prolonged through 21 days after infection. Diabetic mice had fewer inflammatory monocyte/macrophages and CD4+ T cells, which correlated with lower levels of Ccl2 and Cxcl10 expression. Diabetic mice also had lower levels of Tnfa, Il6, Il12b, and Arg1 expression and higher levels of Il17a expression. These data suggest that the increased disease severity observed in individuals with MERS and comorbid type 2 diabetes is likely due to a dysregulated immune response, which results in more severe and prolonged lung pathology.


Assuntos
Infecções por Coronavirus/imunologia , Diabetes Mellitus Tipo 2/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Quimiocina CCL2/análise , Quimiocina CCL2/metabolismo , Quimiocina CXCL10/análise , Quimiocina CXCL10/metabolismo , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Dieta Hiperlipídica/efeitos adversos , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Pulmão/imunologia , Pulmão/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Monócitos/imunologia , Monócitos/metabolismo , Fatores de Risco , Índice de Gravidade de Doença
19.
J Gerontol A Biol Sci Med Sci ; 74(6): 929-935, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-30629126

RESUMO

BACKGROUND: Increasing protein content of the diet might be an effective strategy to preserve muscle mass in older adults undergoing caloric restriction, thereby preserving muscle function. METHODS: Ninety-six older adults (70.3 ± 3.7 years, 74% women, 27% African American) with obesity (35.4 ± 3.3 kg/m2; 47% total body fat) were randomized to a 6-month higher protein (providing 1.2-1.5 g/kg/d) weight loss (WL) program, utilizing the Medifast 4&2&1 Plan, or to weight stability (WS). Dual-energy x-ray absorptiometry-acquired total body mass and composition, and fast gait speed over 400 m was assessed at baseline, 3, and 6 months. RESULTS: At baseline, dual-energy x-ray absorptiometry-acquired total body, fat, and lean masses were 95.9 ± 14.6, 44.6 ± 7.6, and 48.7 ± 9.5 kg, respectively, and 400-m gait speed was 1.17 ± 0.20 m/s. Total body mass was significantly reduced in the WL group (-8.17 [-9.56, -6.77] kg) compared with the WS group (-1.16 [-2.59, 0.27] kg), with 87% of total mass lost as fat (WL: -7.1 [-8.1, -6.1] kg; -15.9% change from baseline). A differential treatment effect was not observed for change in lean mass (WL: -0.81 [-1.40, -0.23] kg vs WS: -0.24 [-0.85, 0.36] kg). Four-hundred-meter gait speed was also unchanged from baseline although trends suggest slightly increased gait speed in the WL group [0.01 (-0.02, 0.04) m/s] compared with the WS group [-0.02 (-0.05, 0.01) m/s]. CONCLUSION: Intentional weight loss using a high-protein diet is effective in producing significant total body mass and fat mass loss, while helping preserve lean body mass and mobility, in relatively high-functioning older adults with obesity.


Assuntos
Composição Corporal , Restrição Calórica , Proteínas Alimentares/administração & dosagem , Obesidade/dietoterapia , Absorciometria de Fóton , Idoso , Índice de Massa Corporal , Feminino , Humanos , Masculino , Programas de Redução de Peso
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