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1.
PLoS One ; 15(10): e0240004, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33002032

RESUMO

The SARS-CoV-2 virus has caused a pandemic and is public health emergency of international concern. As of now, no registered therapies are available for treatment of coronavirus infection. The viral infection depends on the attachment of spike (S) glycoprotein to human cell receptor angiotensin-converting enzyme 2 (ACE2). We have designed a protein inhibitor (ΔABP-D25Y) targeting S protein using computational approach. The inhibitor consists of two α helical peptides homologues to protease domain (PD) of ACE2. Docking studies and molecular dynamic simulation revealed that the inhibitor binds exclusively at the ACE2 binding site of S protein. The computed binding affinity of the inhibitor is higher than the ACE2 and thus will likely out compete ACE2 for binding to S protein. Hence, the proposed inhibitor ΔABP-D25Y could be a potential blocker of S protein and receptor binding domain (RBD) attachment.


Assuntos
Antivirais/química , Betacoronavirus/efeitos dos fármacos , Desenho de Fármacos , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Homologia Estrutural de Proteína , Sítios de Ligação , Simulação por Computador , Infecções por Coronavirus , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Pandemias , Peptidil Dipeptidase A/química , Pneumonia Viral , Domínios Proteicos
2.
Biomed Res Int ; 2020: 5324560, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029513

RESUMO

The ongoing global pandemic caused by the human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions of people and claimed hundreds of thousands of lives. The absence of approved therapeutics to combat this disease threatens the health of all persons on earth and could cause catastrophic damage to society. New drugs are therefore urgently required to bring relief to people everywhere. In addition to repurposing existing drugs, natural products provide an interesting alternative due to their widespread use in all cultures of the world. In this study, alkaloids from Cryptolepis sanguinolenta have been investigated for their ability to inhibit two of the main proteins in SARS-CoV-2, the main protease and the RNA-dependent RNA polymerase, using in silico methods. Molecular docking was used to assess binding potential of the alkaloids to the viral proteins whereas molecular dynamics was used to evaluate stability of the binding event. The results of the study indicate that all 13 alkaloids bind strongly to the main protease and RNA-dependent RNA polymerase with binding energies ranging from -6.7 to -10.6 kcal/mol. In particular, cryptomisrine, cryptospirolepine, cryptoquindoline, and biscryptolepine exhibited very strong inhibitory potential towards both proteins. Results from the molecular dynamics study revealed that a stable protein-ligand complex is formed upon binding. Alkaloids from Cryptolepis sanguinolenta therefore represent a promising class of compounds that could serve as lead compounds in the search for a cure for the corona virus disease.


Assuntos
Alcaloides/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Cryptolepis/química , Pneumonia Viral/tratamento farmacológico , Proteínas Virais/antagonistas & inibidores , Alcaloides/química , Antivirais/química , Antivirais/farmacologia , Betacoronavirus/enzimologia , Simulação por Computador , Infecções por Coronavirus/virologia , Cisteína Endopeptidases , Avaliação Pré-Clínica de Medicamentos , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Pandemias , Pneumonia Viral/virologia , Relação Quantitativa Estrutura-Atividade , Quinolinas/química , Quinolinas/farmacologia , RNA Replicase/antagonistas & inibidores , Proteínas não Estruturais Virais/antagonistas & inibidores
4.
Sci Total Environ ; 746: 142090, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33027870

RESUMO

Transmission mechanics of infectious pathogen in various environments are of great complexity and has always been attracting many researchers' attention. As a cost-effective and powerful method, Computational Fluid Dynamics (CFD) plays an important role in numerically solving environmental fluid mechanics. Besides, with the development of computer science, an increasing number of researchers start to analyze pathogen transmission by using CFD methods. Inspired by the impact of COVID-19, this review summarizes research works of pathogen transmission based on CFD methods with different models and algorithms. Defining the pathogen as the particle or gaseous in CFD simulation is a common method and epidemic models are used in some investigations to rise the authenticity of calculation. Although it is not so difficult to describe the physical characteristics of pathogens, how to describe the biological characteristics of it is still a big challenge in the CFD simulation. A series of investigations which analyzed pathogen transmission in different environments (hospital, teaching building, etc) demonstrated the effect of airflow on pathogen transmission and emphasized the importance of reasonable ventilation. Finally, this review presented three advanced methods: LBM method, Porous Media method, and Web-based forecasting method. Although CFD methods mentioned in this review may not alleviate the current pandemic situation, it helps researchers realize the transmission mechanisms of pathogens like viruses and bacteria and provides guidelines for reducing infection risk in epidemic or pandemic situations.


Assuntos
Infecções por Coronavirus , Hidrodinâmica , Pandemias , Pneumonia Viral , Betacoronavirus , Simulação por Computador , Infecções por Coronavirus/transmissão , Pneumonia Viral/transmissão , Ventilação
5.
Comput Math Methods Med ; 2020: 9017157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029196

RESUMO

This paper deals with the mathematical modeling and numerical simulations related to the coronavirus dynamics. A description is developed based on the framework of the susceptible-exposed-infectious-removed model. Initially, a model verification is carried out calibrating system parameters with data from China, Italy, Iran, and Brazil. Results show the model capability to predict infectious evolution. Afterward, numerical simulations are performed in order to analyze different scenarios of COVID-19 in Brazil. Results show the importance of the governmental and individual actions to control the number and the period of the critical situations related to the pandemic.


Assuntos
Simulação por Computador , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Algoritmos , Betacoronavirus , Brasil/epidemiologia , China/epidemiologia , Doenças Transmissíveis/epidemiologia , Humanos , Irã (Geográfico)/epidemiologia , Itália/epidemiologia , Modelos Teóricos , Pandemias , Informática em Saúde Pública , Reprodutibilidade dos Testes
6.
BMC Infect Dis ; 20(1): 643, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873241

RESUMO

BACKGROUND: The transmission features and the feasibility of containing shigellosis remain unclear among a population-based study in China. METHODS: A population-based Susceptible - Exposed - Infectious / Asymptomatic - Recovered (SEIAR) model was built including decreasing the infectious period (DIP) or isolation of shigellosis cases. We analyzed the distribution of the reported shigellosis cases in Hubei Province, China from January 2005 to December 2017, and divided the time series into several stages according to the heterogeneity of reported incidence during the period. In each stage, an epidemic season was selected for the modelling and assessing the effectiveness of DIP and case isolation. RESULTS: A total of 130,770 shigellosis cases were reported in Hubei Province. The median of Reff was 1.13 (range: 0.86-1.21), 1.10 (range: 0.91-1.13), 1.09 (range: 0.92-1.92), and 1.03 (range: 0.94-1.22) in 2005-2006 season, 2010-2011 season, 2013-2014 season, and 2016-2017 season, respectively. The reported incidence decreased significantly (trend χ2 = 8260.41, P <  0.001) among four stages. The incidence of shigellosis decreased sharply when DIP implemented in three scenarios (γ = 0.1, 0.1429, 0.3333) and when proportion of case isolation increased. CONCLUSIONS: Year heterogeneity of reported shigellosis incidence exists in Hubei Province. It is feasible to contain the transmission by implementing DIP and case isolation.


Assuntos
Disenteria Bacilar/epidemiologia , Epidemias , Modelos Teóricos , Infecções Assintomáticas , China/epidemiologia , Simulação por Computador , Coleta de Dados , Disenteria Bacilar/prevenção & controle , Disenteria Bacilar/transmissão , Estudos de Viabilidade , Humanos , Incidência , Estações do Ano
7.
Rev Peru Med Exp Salud Publica ; 37(2): 195-202, 2020.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-32876206

RESUMO

OBJECTIVES: To determine the probability of controlling the outbreak of COVID-19 in Peru, in a pre- and post-quarantine scenario using mathematical simulation models. MATERIALS AND METHODS: Outbreak si mulations for the COVID-19 pandemic are performed, using stochastic equations under the following assumptions: a pre-quarantine population R0 of 2.7 or 3.5, a post-quarantine R0 of 1.5, 2 or 2.7, 18% or 40%, of asymptomatic positives and a maximum response capacity of 50 or 150 patients in the intensive care units. The success of isolation and contact tracing is evaluated, no other mitigation measures are included. RESULTS: In the pre-quarantine stage, success in controlling more than 80% of the simulations occurred only if the isolation of positive cases was implemented from the first case, after which there was less than 40% probability of success. In post-quarantine, with 60 positive cases it is necessary to isolate them early, track all of their contacts and decrease the R0 to 1.5 for outbreak control to be successful in more than 80% of cases. Other scenarios have a low probability of success. CONCLUSIONS: The control of the outbreak in Peru during pre-quarantine stage demanded requirements that were difficult to comply with, therefore quarantine was necessary; to successfully suspend it would require a significant reduction in the spread of the disease, early isolation of positives and follow-up of all contacts of positive patients.


Assuntos
Simulação por Computador , Infecções por Coronavirus/epidemiologia , Surtos de Doenças/prevenção & controle , Pneumonia Viral/epidemiologia , Busca de Comunicante/métodos , Infecções por Coronavirus/prevenção & controle , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Modelos Teóricos , Pandemias/prevenção & controle , Peru/epidemiologia , Pneumonia Viral/prevenção & controle , Probabilidade , Quarentena
8.
Cien Saude Colet ; 25(9): 3437-3444, 2020 Sep.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32876245

RESUMO

The COVID-19 pandemic poses difficulties for long-term care institutions for the elderly, with increased mortality rates for the residents. This study aims to estimate the impact of COVID-19 on mortality of institutionalized elderly in Brazil. Estimates of the percentage of elderly deaths occurring in care homes were calculated for Brazil, States and Regions using estimates for the total number of deaths. The estimation was based upon information available for other countries. The weighted percentage was 44.7% and 107,538 COVID-19 deaths were estimated for the elderly in these institutions in Brazil in 2020. Higher numbers of deaths were expected in the Southeast Region (48,779 deaths), followed by the Northeast Region (28,451 deaths); São Paulo was the most affected State (24,500 deaths). The strong impact of COVID-19 on the elderly population living in long-term care facilities is clear. Estimates for the country exceeded 100,000 elderly people, potentially the most fragile and vulnerable, and are based upon a conservative number of total deaths, in view of other estimates and the alarming situation of death growth in Brazil from COVID-19.


Assuntos
Infecções por Coronavirus/mortalidade , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Assistência de Longa Duração , Pneumonia Viral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Simulação por Computador , Infecções por Coronavirus/epidemiologia , Estudos Transversais , Humanos , Institucionalização/estatística & dados numéricos , Pandemias , Pneumonia Viral/epidemiologia
9.
Eur J Epidemiol ; 35(8): 749-761, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32888169

RESUMO

The global pandemic of the 2019-nCov requires the evaluation of policy interventions to mitigate future social and economic costs of quarantine measures worldwide. We propose an epidemiological model for forecasting and policy evaluation which incorporates new data in real-time through variational data assimilation. We analyze and discuss infection rates in the UK, US and Italy. We furthermore develop a custom compartmental SIR model fit to variables related to the available data of the pandemic, named SITR model, which allows for more granular inference on infection numbers. We compare and discuss model results which conducts updates as new observations become available. A hybrid data assimilation approach is applied to make results robust to initial conditions and measurement errors in the data. We use the model to conduct inference on infection numbers as well as parameters such as the disease transmissibility rate or the rate of recovery. The parameterisation of the model is parsimonious and extendable, allowing for the incorporation of additional data and parameters of interest. This allows for scalability and the extension of the model to other locations or the adaption of novel data sources.


Assuntos
Infecções por Coronavirus/epidemiologia , Previsões , Pandemias , Pneumonia Viral/epidemiologia , Informática em Saúde Pública/métodos , Teorema de Bayes , Betacoronavirus , Simulação por Computador , Surtos de Doenças , Humanos , Itália/epidemiologia , Modelos Biológicos , Modelos Estatísticos , Quarentena , Reino Unido/epidemiologia , Estados Unidos/epidemiologia
10.
J Korean Med Sci ; 35(35): e321, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32893522

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has posed significant global public health challenges and created a substantial economic burden. Korea has experienced an extensive outbreak, which was linked to a religion-related super-spreading event. However, the implementation of various non-pharmaceutical interventions (NPIs), including social distancing, spring semester postponing, and extensive testing and contact tracing controlled the epidemic. Herein, we estimated the effectiveness of each NPI using a simulation model. METHODS: A compartment model with a susceptible-exposed-infectious-quarantined-hospitalized structure was employed. Using the Monte-Carlo-Markov-Chain algorithm with Gibbs' sampling method, we estimated the time-varying effective contact rate to calibrate the model with the reported daily new confirmed cases from February 12th to March 31st (7 weeks). Moreover, we conducted scenario analyses by adjusting the parameters to estimate the effectiveness of NPI. RESULTS: Relaxed social distancing among adults would have increased the number of cases 27.4-fold until the end of March. Spring semester non-postponement would have increased the number of cases 1.7-fold among individuals aged 0-19, while lower quarantine and detection rates would have increased the number of cases 1.4-fold. CONCLUSION: Among the three NPI measures, social distancing in adults showed the highest effectiveness. The substantial effect of social distancing should be considered when preparing for the 2nd wave of COVID-19.


Assuntos
Controle de Doenças Transmissíveis/métodos , Busca de Comunicante/métodos , Infecções por Coronavirus/transmissão , Programas de Rastreamento/métodos , Pneumonia Viral/transmissão , Distância Social , Betacoronavirus , Simulação por Computador , Exposição Ambiental/prevenção & controle , Humanos , Cadeias de Markov , Modelos Teóricos , Método de Monte Carlo , Pandemias , Prática de Saúde Pública/legislação & jurisprudência , República da Coreia
11.
Comput Math Methods Med ; 2020: 1352982, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908574

RESUMO

The current emergence of coronavirus (SARS-CoV-2) puts the world in threat. The structural research on the receptor recognition by SARS-CoV-2 has identified the key interactions between SARS-CoV-2 spike protein and its host (epithelial cell) receptor, also known as angiotensin-converting enzyme 2 (ACE2). It controls both the cross-species and human-to-human transmissions of SARS-CoV-2. In view of this, we propose and analyze a mathematical model for investigating the effect of CTL responses over the viral mutation to control the viral infection when a postinfection immunostimulant drug (pidotimod) is administered at regular intervals. Dynamics of the system with and without impulses have been analyzed using the basic reproduction number. This study shows that the proper dosing interval and drug dose both are important to eradicate the viral infection.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Modelos Biológicos , Pneumonia Viral/tratamento farmacológico , Ácido Pirrolidonocarboxílico/análogos & derivados , Tiazolidinas/administração & dosagem , Número Básico de Reprodução , Betacoronavirus/genética , Betacoronavirus/imunologia , Simulação por Computador , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Relação Dose-Resposta a Droga , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Conceitos Matemáticos , Mutação , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Ácido Pirrolidonocarboxílico/administração & dosagem , Receptores Virais/fisiologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T Citotóxicos/imunologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-32911738

RESUMO

COVID-19 has posed an unprecedented global public health threat and caused a significant number of severe cases that necessitated long hospitalization and overwhelmed health services in the most affected countries. In response, governments initiated a series of non-pharmaceutical interventions (NPIs) that led to severe economic and social impacts. The effect of these intervention measures on the spread of the COVID-19 pandemic are not well investigated within developing country settings. This study simulated the trajectories of the COVID-19 pandemic curve in Jordan between February and May and assessed the effect of Jordan's strict NPI measures on the spread of COVID-19. A modified susceptible, exposed, infected, and recovered (SEIR) epidemic model was utilized. The compartments in the proposed model categorized the Jordanian population into six deterministic compartments: suspected, exposed, infectious pre-symptomatic, infectious with mild symptoms, infectious with moderate to severe symptoms, and recovered. The GLEAMviz client simulator was used to run the simulation model. Epidemic curves were plotted for estimated COVID-19 cases in the simulation model, and compared against the reported cases. The simulation model estimated the highest number of total daily new COVID-19 cases, in the pre-symptomatic compartmental state, to be 65 cases, with an epidemic curve growing to its peak in 49 days and terminating in a duration of 83 days, and a total simulated cumulative case count of 1048 cases. The curve representing the number of actual reported cases in Jordan showed a good pattern compatibility to that in the mild and moderate to severe compartmental states. The reproduction number under the NPIs was reduced from 5.6 to less than one. NPIs in Jordan seem to be effective in controlling the COVID-19 epidemic and reducing the reproduction rate. Early strict intervention measures showed evidence of containing and suppressing the disease.


Assuntos
Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Betacoronavirus , Simulação por Computador , Humanos , Jordânia/epidemiologia , Modelos Estatísticos , Índice de Gravidade de Doença
13.
J Biol Dyn ; 14(1): 748-766, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32990177

RESUMO

The outbreak of COVID-19 was first experienced in Wuhan City, China, during December 2019 before it rapidly spread over globally. This paper has proposed a mathematical model for studying its transmission dynamics in the presence of face mask wearing and hospitalization services of human population in Tanzania. Disease-free and endemic equilibria were determined and subsequently their local and global stabilities were carried out. The trace-determinant approach was used in the local stability of disease-free equilibrium point while Lyapunov function technique was used to determine the global stability of both disease-free and endemic equilibrium points. Basic reproduction number, R 0 , was determined in which its numerical results revealed that, in the presence of face masks wearing and medication services or hospitalization as preventive measure for its transmission, R 0 = 0.698 while in their absence R 0 = 3.8 . This supports its analytical solution that the disease-free equilibrium point E 0 is asymptotically stable whenever R 0 < 1 , while endemic equilibrium point E ∗ is globally asymptotically stable for R 0 > 1 . Therefore, this paper proves the necessity of face masks wearing and hospitalization services to COVID-19 patients to contain the disease spread to the population.


Assuntos
Betacoronavirus , Infecções por Coronavirus/transmissão , Modelos Biológicos , Pandemias , Pneumonia Viral/transmissão , Número Básico de Reprodução , Simulação por Computador , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Suscetibilidade a Doenças , Doenças Endêmicas/prevenção & controle , Doenças Endêmicas/estatística & dados numéricos , Humanos , Máscaras/estatística & dados numéricos , Conceitos Matemáticos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Tanzânia/epidemiologia
14.
J Clin Virol ; 131: 104581, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32889496

RESUMO

INTRODUCTION: During the first month of the SARS-CoV-2 outbreak, rapid development of PCR-based diagnostic tests became a global priority so that timely diagnosis, isolation, and contact tracing could minimize the advancing pandemic surge. Designing these tests for broad, long-term detection was complicated by limited information about the novel virus' genome sequence and how it might mutate during global spread and adaptation to humans. METHODS: We assessed eight widely adopted lab developed PCR tests for SARS-CoV-2 against 15,001 SARS-CoV-2 genome sequences. Using a custom bioinformatic pipeline called PCR_strainer, we identified all mismatches and sequence variants in genome locations targeted by 15 sets of primer/probe oligonucleotides from these assays. RESULTS: For 12 out of 15 primer/probe sets, over 98 % of SARS-CoV-2 genomes had no mismatches. Two primer/probe sets contained a single mismatch in the reverse primer that was present in over 99 % of genomes. One primer/probe set targeted a location with extensive polymorphisms with 23 sequence observed variants at the forward primer location. One of these variants, which contains three nucleotide mismatches, arose in February as part of the emergence of a viral clade and was present in 18.8 % of the genomes we analyzed. DISCUSSION: Most early PCR diagnostic tests for SARS-CoV-2 remain inclusive of circulating viral diversity, but three assays with extensive mismatches highlight assay design challenges for novel pathogens and provide valuable lessons for PCR assay design during future outbreaks. Our bioinformatics pipeline is also presented as a useful general-purpose tool for assessing PCR diagnostics assays against circulating strains.


Assuntos
Betacoronavirus/genética , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Oligonucleotídeos/genética , Pneumonia Viral/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Biologia Computacional , Simulação por Computador , Infecções por Coronavirus/virologia , Genoma Viral , Humanos , Pandemias , Pneumonia Viral/virologia , RNA Viral , Sensibilidade e Especificidade
15.
PLoS One ; 15(9): e0239647, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970745

RESUMO

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the most significant global health crisis of the 21st century. The aim of this study was to develop a model to simulate the effect of undocumented infections, seasonal infectivity, immunity, and non-pharmaceutical interventions (NPIs) on the transmission, morbidity, and mortality of SARS-CoV-2 in New York State (NYS) based on data collected between March 4 and April 28, 2020. Simulations predict that undocumented infections significantly contribute to infectivity, NPIs are effective in reducing morbidity and mortality, and relaxation >50% of NPIs from initial lock-down levels may result in tens-of-thousands more deaths. Endemic infection is likely to occur in the absence of sustained immunity. As a result, until an effective vaccine or other effective pharmaceutical intervention is developed, the risks of significantly reducing NPIs should be carefully considered. This study employs modelling to simulate fundamental characteristics of SARS-CoV-2 transmission, which can help policymakers navigate combating this virus in the coming years.


Assuntos
Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Doenças não Diagnosticadas/epidemiologia , Betacoronavirus , Simulação por Computador , Infecções por Coronavirus/transmissão , Previsões , Humanos , Imunidade , Modelos Teóricos , New York/epidemiologia , Pandemias , Pneumonia Viral/transmissão , Estações do Ano , Doenças não Diagnosticadas/virologia
16.
Cell ; 182(6): 1366-1371, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32905783

RESUMO

Operation Outbreak (OO) is a Bluetooth-based simulation platform that teaches students how pathogens spread and the impact of interventions, thereby facilitating the safe reopening of schools. OO also generates data to inform epidemiological models and prevent future outbreaks. Before SARS-CoV-2 was reported, we repeatedly simulated a virus with similar features, correctly predicting many human behaviors later observed during the pandemic.


Assuntos
Simulação por Computador , Instrução por Computador/métodos , Busca de Comunicante/métodos , Infecções por Coronavirus/epidemiologia , Epidemiologia/educação , Pneumonia Viral/epidemiologia , Número Básico de Reprodução , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Humanos , Aplicativos Móveis , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Smartphone
17.
Oncology (Williston Park) ; 34(9): 343, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32965661

RESUMO

During the height of the coronavirus disease 2019(COVID-19) pandemic, many health care facilities needed to focus on screening for and treating patients with known or suspected COVID-19. This resulted in the diversion of health care workers and resources.


Assuntos
Infecções por Coronavirus , Diagnóstico Tardio , Detecção Precoce de Câncer/estatística & dados numéricos , Neoplasias/diagnóstico , Neoplasias/mortalidade , Pandemias , Pneumonia Viral , Betacoronavirus , Simulação por Computador , Humanos
18.
Nat Commun ; 11(1): 4883, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985528

RESUMO

Early stages of the novel coronavirus disease (COVID-19) are associated with silent hypoxia and poor oxygenation despite relatively minor parenchymal involvement. Although speculated that such paradoxical findings may be explained by impaired hypoxic pulmonary vasoconstriction in infected lung regions, no studies have determined whether such extreme degrees of perfusion redistribution are physiologically plausible, and increasing attention is directed towards thrombotic microembolism as the underlying cause of hypoxemia. Herein, a mathematical model demonstrates that the large amount of pulmonary venous admixture observed in patients with early COVID-19 can be reasonably explained by a combination of pulmonary embolism, ventilation-perfusion mismatching in the noninjured lung, and normal perfusion of the relatively small fraction of injured lung. Although underlying perfusion heterogeneity exacerbates existing shunt and ventilation-perfusion mismatch in the model, the reported hypoxemia severity in early COVID-19 patients is not replicated without either extensive perfusion defects, severe ventilation-perfusion mismatch, or hyperperfusion of nonoxygenated regions.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Hipóxia/etiologia , Hipóxia/fisiopatologia , Pneumopatias/etiologia , Pneumopatias/fisiopatologia , Pulmão/irrigação sanguínea , Pulmão/fisiopatologia , Modelos Biológicos , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Circulação Pulmonar/fisiologia , Simulação por Computador , Infecções por Coronavirus/epidemiologia , Humanos , Hipóxia/terapia , Pneumopatias/terapia , Conceitos Matemáticos , Modelos Cardiovasculares , Oxigenoterapia , Pandemias , Pneumonia Viral/epidemiologia , Fatores de Tempo , Vasoconstrição/fisiologia , Vasodilatação/fisiologia , Relação Ventilação-Perfusão/fisiologia
19.
SAR QSAR Environ Res ; 31(10): 761-784, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32867537

RESUMO

The free COOH group of conventional NSAIDs is a structural feature for non-selective cyclooxygenase (COX) inhibition and the molecular cause of their gastrointestinal (GI) toxicity. In this context, an in house database of synthesizable ester prodrugs of some well-known NSAIDs was developed by combining their -COOH group with -OH of a newly identified antioxidant 4-(1H-benzo[d]imidazol-2-yl)phenol (BZ). The antioxidant potential of BZ was unveiled through in silico PASS prediction and in vitro/in vivo evaluation. The in house database of NSAIDs-BZ prodrugs was first subjected to screening with our previously reported pharmacophore models of hCES1 (AAHRR.430) and hCES2 (AHHR.21) for determining hydrolytic susceptibility. Biotransformation behaviour of screened prodrugs was then assessed by using QM/MM and sterimol parameterization, followed by ADMET calculations to predict the drug likeness. On the basis of in silico results, five prodrugs were duly synthesized and the best three were subject to the in vivo evaluation for their anti-inflammatory, analgesic, antioxidant activities, and ulcerogenic index. Among these prodrugs, BN2 and BN5 displayed better anti-inflammatory and analgesics potential in comparison to their parent drugs. All the prodrugs were found to be gastro sparing in the rat model and significantly improved the levels of oxidative stress biomarkers in both blood plasma as well as gastric homogenate.


Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Imidazóis/química , Fenóis/química , Pró-Fármacos/síntese química , Relação Quantitativa Estrutura-Atividade , Simulação por Computador
20.
SAR QSAR Environ Res ; 31(9): 697-715, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878494

RESUMO

Azo dyes are a group of chemical moieties joined by azo (-N=N-) group with potential usefulness in different industrial applications. But these dyes are not devoid of hazardous consequence because of poor affinity for the fibre and discharge into the water stream. The chemical aspects of 72 azo dyes towards cellulose fibre in terms of their affinity by QSPR have been explored in the present work. We have employed two approaches, namely balance of correlation without IIC (TF1) and balance of correlation with IIC (TF2), to generate 16 QSAR models from 8 splits. The determination coefficient of calibration and validation set was found higher when the QSPR models were developed using the index of ideality correlation (IIC) parameter (TF2). The model developed with TF2 for split 3 was considered as a prominent model because the determination coefficient of the validation set was maximum (r 2 = 0.9468). The applicability domain (AD) was also analysed based on 'statistical defect', d(A) for a SMILES attribute. The mechanistic interpretation was done by identifying the SMILES attributes responsible for the promoter of endpoint increase and promoter of endpoint decrease. These SMILES attributes were applied to design 15 new dyes with higher affinity for cellulose fibre.


Assuntos
Compostos Azo/química , Celulose/química , Corantes/química , Relação Quantitativa Estrutura-Atividade , Adsorção , Simulação por Computador , Método de Monte Carlo
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