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1.
Signal Transduct Target Ther ; 5(1): 125, 2020 07 13.
Artículo en Inglés | MEDLINE | ID: covidwho-654479

RESUMEN

Stress proteins (SPs) including heat-shock proteins (HSPs), RNA chaperones, and ER associated stress proteins are molecular chaperones essential for cellular homeostasis. The major functions of HSPs include chaperoning misfolded or unfolded polypeptides, protecting cells from toxic stress, and presenting immune and inflammatory cytokines. Regarded as a double-edged sword, HSPs also cooperate with numerous viruses and cancer cells to promote their survival. RNA chaperones are a group of heterogeneous nuclear ribonucleoproteins (hnRNPs), which are essential factors for manipulating both the functions and metabolisms of pre-mRNAs/hnRNAs transcribed by RNA polymerase II. hnRNPs involve in a large number of cellular processes, including chromatin remodelling, transcription regulation, RNP assembly and stabilization, RNA export, virus replication, histone-like nucleoid structuring, and even intracellular immunity. Dysregulation of stress proteins is associated with many human diseases including human cancer, cardiovascular diseases, neurodegenerative diseases (e.g., Parkinson's diseases, Alzheimer disease), stroke and infectious diseases. In this review, we summarized the biologic function of stress proteins, and current progress on their mechanisms related to virus reproduction and diseases caused by virus infections. As SPs also attract a great interest as potential antiviral targets (e.g., COVID-19), we also discuss the present progress and challenges in this area of HSP-based drug development, as well as with compounds already under clinical evaluation.


Asunto(s)
Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Proteínas de Choque Térmico/genética , Ribonucleoproteínas Nucleares Heterogéneas/genética , Interacciones Huésped-Patógeno/efectos de los fármacos , Neumonía Viral/tratamiento farmacológico , Antivirales/síntesis química , Betacoronavirus/genética , Betacoronavirus/patogenicidad , Ensamble y Desensamble de Cromatina/efectos de los fármacos , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Regulación de la Expresión Génica , Proteínas de Choque Térmico/agonistas , Proteínas de Choque Térmico/antagonistas & inhibidores , Proteínas de Choque Térmico/metabolismo , Ribonucleoproteínas Nucleares Heterogéneas/agonistas , Ribonucleoproteínas Nucleares Heterogéneas/antagonistas & inhibidores , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Interacciones Huésped-Patógeno/genética , Humanos , Terapia Molecular Dirigida/métodos , Pandemias , Neumonía Viral/genética , Neumonía Viral/patología , Neumonía Viral/virología , ARN Polimerasa II/genética , ARN Polimerasa II/metabolismo , Precursores del ARN/genética , Precursores del ARN/metabolismo , Índice de Severidad de la Enfermedad , Transducción de Señal , Transcripción Genética/efectos de los fármacos , Replicación Viral/efectos de los fármacos
2.
Nat Commun ; 11(1): 2750, 2020 06 02.
Artículo en Inglés | MEDLINE | ID: covidwho-680538

RESUMEN

Influenza viruses annually kill 290,000-650,000 people worldwide. Antivirals can reduce death tolls. Baloxavir, the recently approved influenza antiviral, inhibits initiation of viral mRNA synthesis, whereas oseltamivir, an older drug, inhibits release of virus progeny. Baloxavir blocks virus replication more rapidly and completely than oseltamivir, reducing the duration of infectiousness. Hence, early baloxavir treatment may indirectly prevent transmission. Here, we estimate impacts of ramping up and accelerating baloxavir treatment on population-level incidence using a new model that links viral load dynamics from clinical trial data to between-host transmission. We estimate that ~22 million infections and >6,000 deaths would have been averted in the 2017-2018 epidemic season by administering baloxavir to 30% of infected cases within 48 h after symptom onset. Treatment within 24 h would almost double the impact. Consequently, scaling up early baloxavir treatment would substantially reduce influenza morbidity and mortality every year. The development of antivirals against the SARS-CoV2 virus that function like baloxavir might similarly curtail transmission and save lives.


Asunto(s)
Antivirales/uso terapéutico , Epidemias , Gripe Humana/tratamiento farmacológico , Orthomyxoviridae/efectos de los fármacos , Oxazinas/uso terapéutico , Piridinas/uso terapéutico , Tiepinas/uso terapéutico , Triazinas/uso terapéutico , Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , Proliferación Celular , Infecciones por Coronavirus/tratamiento farmacológico , Humanos , Gripe Humana/virología , Oseltamivir/farmacología , Oseltamivir/uso terapéutico , Oxazinas/farmacología , Pandemias , Neumonía Viral/tratamiento farmacológico , Salud Pública , Piridinas/farmacología , ARN Mensajero/metabolismo , Estaciones del Año , Tiepinas/farmacología , Triazinas/farmacología , Carga Viral , Replicación Viral/efectos de los fármacos
4.
ACS Nano ; 14(8): 9364-9388, 2020 08 25.
Artículo en Inglés | MEDLINE | ID: covidwho-646861

RESUMEN

The SARS-Cov-2 pandemic has spread worldwide during 2020, setting up an uncertain start of this decade. The measures to contain infection taken by many governments have been extremely severe by imposing home lockdown and industrial production shutdown, making this the biggest crisis since the second world war. Additionally, the continuous colonization of wild natural lands may touch unknown virus reservoirs, causing the spread of epidemics. Apart from SARS-Cov-2, the recent history has seen the spread of several viral pandemics such as H2N2 and H3N3 flu, HIV, and SARS, while MERS and Ebola viruses are considered still in a prepandemic phase. Hard nanomaterials (HNMs) have been recently used as antimicrobial agents, potentially being next-generation drugs to fight viral infections. HNMs can block infection at early (disinfection, entrance inhibition) and middle (inside the host cells) stages and are also able to mitigate the immune response. This review is focused on the application of HNMs as antiviral agents. In particular, mechanisms of actions, biological outputs, and limitations for each HNM will be systematically presented and analyzed from a material chemistry point-of-view. The antiviral activity will be discussed in the context of the different pandemic viruses. We acknowledge that HNM antiviral research is still at its early stage, however, we believe that this field will rapidly blossom in the next period.


Asunto(s)
Antivirales/uso terapéutico , Betacoronavirus , Infecciones por Coronavirus/terapia , Nanoestructuras/uso terapéutico , Pandemias , Neumonía Viral/terapia , Inmunidad Adaptativa , Betacoronavirus/efectos de los fármacos , Betacoronavirus/fisiología , Betacoronavirus/ultraestructura , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Sistemas de Liberación de Medicamentos , Fulerenos/uso terapéutico , Interacciones Microbiota-Huesped/efectos de los fármacos , Humanos , Inmunidad Innata , Nanopartículas del Metal/uso terapéutico , Modelos Biológicos , Nanotecnología , Neumonía Viral/epidemiología , Neumonía Viral/virología , Especies Reactivas de Oxígeno/uso terapéutico , Internalización del Virus/efectos de los fármacos
5.
Nano Lett ; 20(7): 5367-5375, 2020 07 08.
Artículo en Inglés | MEDLINE | ID: covidwho-628240

RESUMEN

Geometry-matching has been known to benefit the formation of stable biological interactions in natural systems. Herein, we report that the spiky nanostructures with matched topography to the influenza A virus (IAV) virions could be used to design next-generation advanced virus inhibitors. We demonstrated that nanostructures with spikes between 5 and 10 nm bind significantly better to virions than smooth nanoparticles, due to the short spikes inserting into the gaps of glycoproteins of the IAV virion. Furthermore, an erythrocyte membrane (EM) was coated to target the IAV, and the obtained EM-coated nanostructures could efficiently prevent IAV virion binding to the cells and inhibit subsequent infection. In a postinfection study, the EM-coated nanostructures reduced >99.9% virus replication at the cellular nontoxic dosage. We predict that such a combination of geometry-matching topography and cellular membrane coating will also push forward the development of nanoinhibitors for other virus strains, including SARS-CoV-2.


Asunto(s)
Betacoronavirus/ultraestructura , Infecciones por Coronavirus/virología , Nanoestructuras/ultraestructura , Neumonía Viral/virología , Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , Sitios de Unión , Infecciones por Coronavirus/tratamiento farmacológico , Diseño de Fármacos , Humanos , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza A/ultraestructura , Microscopía Electrónica , Modelos Biológicos , Nanotecnología , Pandemias , Neumonía Viral/tratamiento farmacológico , Glicoproteína de la Espiga del Coronavirus/efectos de los fármacos , Glicoproteína de la Espiga del Coronavirus/ultraestructura , Internalización del Virus/efectos de los fármacos
6.
Arch Virol ; 165(9): 1935-1945, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: covidwho-617264

RESUMEN

Plants are a rich source of new antiviral, pharmacologically active agents. The naturally occurring plant alkaloid berberine (BBR) is one of the phytochemicals with a broad range of biological activity, including anticancer, anti-inflammatory and antiviral activity. BBR targets different steps in the viral life cycle and is thus a good candidate for use in novel antiviral drugs and therapies. It has been shown that BBR reduces virus replication and targets specific interactions between the virus and its host. BBR intercalates into DNA and inhibits DNA synthesis and reverse transcriptase activity. It inhibits replication of herpes simplex virus (HSV), human cytomegalovirus (HCMV), human papillomavirus (HPV), and human immunodeficiency virus (HIV). This isoquinoline alkaloid has the ability to regulate the MEK-ERK, AMPK/mTOR, and NF-κB signaling pathways, which are necessary for viral replication. Furthermore, it has been reported that BBR supports the host immune response, thus leading to viral clearance. In this short review, we focus on the most recent studies on the antiviral properties of berberine and its derivatives, which might be promising agents to be considered in future studies in the fight against the current pandemic SARS-CoV-2, the virus that causes COVID-19.


Asunto(s)
Antivirales/farmacología , Berberina/farmacología , Virus/efectos de los fármacos , Animales , Antivirales/química , Berberina/química , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Virosis/virología , Replicación Viral/efectos de los fármacos , Virus/genética , Virus/crecimiento & desarrollo
7.
Int J Mol Med ; 46(3): 903-912, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: covidwho-750592

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) is a novel ß coronavirus that is the etiological agent of the pandemic coronavirus disease 2019 (COVID­19) that at the time of writing (June 16, 2020) has infected almost 6 million people with some 450,000 deaths. These numbers are still rising daily. Most (some 80%) cases of COVID­19 infection are asymptomatic, a substantial number of cases (15%) require hospitalization and an additional fraction of patients (5%) need recovery in intensive care units. Mortality for COVID­19 infection appears to occur globally between 0.1 and 0.5% of infected patients although the frequency of lethality is significantly augmented in the elderly and in patients with other comorbidities. The development of acute respiratory distress syndrome and episodes of thromboembolism that may lead to disseminated intravascular coagulation (DIC) represent the primary causes of lethality during COVID­19 infection. Increasing evidence suggests that thrombotic diathesis is due to multiple derangements of the coagulation system including marked elevation of D­dimer that correlate negatively with survival. We propose here that the thromboembolic events and eventually the development of DIC provoked by SARS­CoV­2 infection may represent a secondary anti­phospholipid antibody syndrome (APS). We will apply both Baconian inductivism and Cartesian deductivism to prove that secondary APS is likely responsible for coagulopathy during the course of COVID­19 infection. Diagnostic and therapeutic implications of this are also discussed.


Asunto(s)
Síndrome Antifosfolípido/patología , Infecciones por Coronavirus/patología , Coagulación Intravascular Diseminada/patología , Neumonía Viral/patología , Tromboembolia/patología , Trombosis/patología , Síndrome Antifosfolípido/inmunología , Antivirales/uso terapéutico , Betacoronavirus , Coagulación Sanguínea/fisiología , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/inmunología , Coagulación Intravascular Diseminada/inmunología , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Pandemias , Fosfolípidos/inmunología , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/inmunología , Tromboembolia/inmunología
8.
Rev Peru Med Exp Salud Publica ; 37(2): 302-311, 2020.
Artículo en Español | MEDLINE | ID: covidwho-749299

RESUMEN

During the first weeks of 2020, cases of SARS-CoV-2 began to be reported outside of China, with a rapid increase in cases and deaths worldwide. SARS-CoV-2 is a positive single-stranded RNA virus, encased in a lipid bilayer derived from the host cell membrane and consists of four structural proteins (S, M, E and N), plus a haemagglutinin-sterase. The binding of the S protein to the ECA2 receptor allows the entry of the virus into the host cell and is a potential therapeutic target. 81% of patients develop mild symptoms, 14% have severe symptoms and 5% require intensive care management. Fever is the most frequent symptom, followed by cough and dyspnea. Most patients do not present leukocytosis, but they do present lymphopenia with sputum cultures that do not show other pathogens. In lung biopsies of severe patients, the most noticeable finding is diffuse alveolar damage. Radiologically, ground glass and alveolar patterns are observed; the lesions being predominantly basal, subpleural, and posterior, with a multifocal peripheral distribution, more affecting the right lower lobe. There is a marked inflammatory response, up to the cytokine storm, in which anti-inflammatory treatment with pulse therapy with methylprednisolone would be indicated. Although there are no large-scale studies regarding the use of chloroquine / hydroxychloroquine, due to the global situation, its use has been authorized for its anti-SARS-CoV-2 and anti-inflammatory effect, which can be potentiated with the use of azithromycin.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Inflamación/virología , Neumonía Viral/epidemiología , Antiinflamatorios/administración & dosificación , Antivirales/administración & dosificación , Cloroquina/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/fisiopatología , Humanos , Hidroxicloroquina/administración & dosificación , Inflamación/tratamiento farmacológico , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/fisiopatología
9.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(4): 586-594, 2020 Apr 30.
Artículo en Chino | MEDLINE | ID: covidwho-749256

RESUMEN

Since the outbreak of coronavirus disease 2019 (COVID-19) in the late 2019, a variety of antiviral drugs have been used in the first-line clinical trial. The Diagnostic and Treatment Protocol for COVID-19 (Trial Version 6) in China recommends chloroquine phosphate for the first time as an anti-coronavirus trial drug. As a classic drug for treatment of malaria and rheumatism, chloroquine phosphate has been used clinically for more than 80 years, and has also shown good results in the treatment of various viral infections. As the plasma drug concentration varies greatly among different races and individuals and due to its narrow treatment window, chloroquine in likely to accumulate in the body to cause toxicity. Among the treatment regimens recommended for COVID-19, reports concerning the safety of a short-term high-dose chloroquine regimen remain scarce. In this review, the authors summarize the current research findings of chloroquine phosphate in the treatment of COVID-19, and examine the pharmacokinetic characteristics, antiviral therapy, the therapeutic mechanism and safety of chloroquine.


Asunto(s)
Betacoronavirus/efectos de los fármacos , Cloroquina/análogos & derivados , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Antivirales , China , Cloroquina/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Humanos , Neumonía Viral/tratamiento farmacológico
10.
Mymensingh Med J ; 29(3): 747-754, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: covidwho-746334

RESUMEN

The sudden outbreak of a novel coronavirus in 2019 in Wuhan, China, that rapidly provoked a global concern, marked as the third attack of corona virus in the human society that affected the global healthcare system as well as the global economy. Until and unless an effective vaccine is discovered against the virus, the pharmacological intervention by different antivirals is in the run for remedy. The aim of this systematic review was to evaluate the role of favipiravir along with its safety and efficacy for the patients who are suffering from severe acute respiratory distress syndrome due to CoronaVirus-2 (SARS-CoV-2) as re-purposeful use. We searched PubMed, EMBASE for randomized controlled trials (RCTs), cilicaltrial.com for registered on going trails to evaluate the pros and cons of using favipiravir in COVID-19. After vigorous searching, screening and sorting of 314 articles for completed and published scientific evidences in electronic database, there were only 2 completed and published randomized control trials (RCT) and 17 ongoing or unpublished trials found until June 2020. The main outcome measures were viral clearance, clinical improvement and adverse events reported and published on 147 patients infected with SARS-CoV2. The 2 completed RCTs showed significantly better treatment effects on disease progression, viral clearance, improved the latency to relief for pyrexia and cough on favipiravir treated patients. Adverse effects caused Favipiravir are mild and manageable. Although 9 more RCTs and cohort studies are supposed to be completed by this time that may unveil some evidence for use of anti-RNA-viral drug favipiravir against influenza or Ebola to re-purposing against COVID-19 as adopted in different treatment guidelines.


Asunto(s)
Amidas/uso terapéutico , Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Reposicionamiento de Medicamentos , Pandemias , Neumonía Viral/tratamiento farmacológico , Pirazinas/uso terapéutico , Betacoronavirus , China , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Humanos , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Resultado del Tratamiento
11.
J Nanobiotechnology ; 18(1): 125, 2020 Sep 05.
Artículo en Inglés | MEDLINE | ID: covidwho-745681

RESUMEN

Incidents of viral outbreaks have increased at an alarming rate over the past decades. The most recent human coronavirus known as COVID-19 (SARS-CoV-2) has already spread around the world and shown R0 values from 2.2 to 2.68. However, the ratio between mortality and number of infections seems to be lower in this case in comparison to other human coronaviruses (such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)). These outbreaks have tested the limits of healthcare systems and have posed serious questions about management using conventional therapies and diagnostic tools. In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis and treatment of COVID-19 and other viral infections. In this review, we discuss the use of nanotechnology for COVID-19 virus management by the development of nano-based materials, such as disinfectants, personal protective equipment, diagnostic systems and nanocarrier systems, for treatments and vaccine development, as well as the challenges and drawbacks that need addressing.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus , Nanotecnología/métodos , Pandemias , Neumonía Viral , Antivirales/administración & dosificación , Betacoronavirus/aislamiento & purificación , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/terapia , Desinfección/métodos , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Humanos , Nanoestructuras/administración & dosificación , Equipo de Protección Personal , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Vacunas Virales/administración & dosificación
12.
Vestn Oftalmol ; 136(4. Vyp. 2): 265-271, 2020.
Artículo en Ruso | MEDLINE | ID: covidwho-745625

RESUMEN

Coronavirus infection is currently en extremely relevant scientific topic due to the emergence of a new serotype that causes a condition identified as Severe Acute Respiratory Syndrome (SARS)-COV-2. Chloroquine and hydroxychloroquine have a long history of use against other infectious diseases, they are available and inexpensive, so the possibility of using them in vivo and in vitro to suppress the infectious agent was examined. Despite the noted therapeutic potential of these drugs, it was necessary to take into account the toxicological aspects that dictate the importance of rational use of 4-aminoquinoline derivatives. This review analyzes literature on the development patterns of hydroxychloroquine retinopathy, basic principles of diagnosis and differentiation of this condition from other types of retinal pathology.


Asunto(s)
Antivirales/uso terapéutico , Betacoronavirus , Neumonía Viral/diagnóstico , Neumonía Viral/tratamiento farmacológico , Diagnóstico Diferencial , Humanos , Hidroxicloroquina/uso terapéutico , Pandemias
13.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(5): 598-602, 2020 May 28.
Artículo en Inglés, Chino | MEDLINE | ID: covidwho-745317

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the outbreak of coronavirus disease 2019 in Wuhan City, China. The SARS-CoV-2 is genetically similar to the coronavirus derived from bat. The SARS-CoV-2, the SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV) all belong to beta coronavirus. Since the outbreak of the coronavirus disease 2019, effective antiviral drugs have become a hot issue in the world. Very little about SARS-CoV-2 is known and there is no precedent for treatment. The National Health Commission has repeatedly revised the diagnosis and treatment guide for the coronavirus disease 2019. The latest guide is "New Coronary Virus-Infected Pneumonia Diagnosis and Treatment Plan (Seventh Trial Version)"(short for Seventh Version of Diagnosis and Treatment Plan). But the use of antiviral drugs is still on trial and no rigorous clinical trials data is available. Hot anti-SARS-CoV-2 drugs include interferon α, ribavirin, lopinavir/ritonavir, chloroquine phosphate, abidol, as well as hydroxychloroquine sulfate and remdesivir. But the later 2 drugs aren't mentioned in the Seventh Version of Diagnosis and Treatment Plan.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Betacoronavirus , China , Humanos , Pandemias , Guías de Práctica Clínica como Asunto
17.
Br J Hosp Med (Lond) ; 81(8): 1-10, 2020 Aug 02.
Artículo en Inglés | MEDLINE | ID: covidwho-743028

RESUMEN

The COVID-19 pandemic has predominantly affected the adult population. The disease is less well-defined in children (≤18 years). This review summarises the current understanding of the epidemiology, clinical manifestations, and management of COVID-19 in children and adolescents. The prevalence of COVID-19 is significantly lower in children than adults, but paediatric disease is likely underdiagnosed as a result of the high numbers of asymptomatic or mild cases. Children are vulnerable to family cluster outbreaks, but are unlikely to be index cases within a household. Vertical transmission or breast milk transmission are yet to be proven. Between 10 and 90% of paediatric COVID-19 cases are asymptomatic. Symptomatic cases typically present with mild symptoms, including cough, fever and sore throat. Intensive care admission and mortality are rare. Paediatric multisystem inflammatory syndrome temporally associated with COVID-19 is a rare, but severe, newly emerging phenotype. At present, there is no specific treatment for COVID-19 in adults or children; management is usually supportive. For severe or critical disease, including paediatric multisystem inflammatory syndrome temporally associated with COVID-19, the decision to start antiviral or immunomodulatory therapy should be on a case-by-case basis; in the UK, this should be done within a clinical trial. Further research is needed into both the disease course and treatment of paediatric COVID-19.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/fisiopatología , Neumonía Viral/epidemiología , Neumonía Viral/fisiopatología , Adolescente , Corticoesteroides/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus , Niño , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Oxigenación por Membrana Extracorpórea , Hemofiltración , Humanos , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Mortalidad , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/tratamiento farmacológico , Reacción en Cadena en Tiempo Real de la Polimerasa , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología
18.
Molecules ; 25(17)2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: covidwho-742825

RESUMEN

Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , Betacoronavirus/fisiología , Productos Biológicos/farmacología , Infecciones por Coronavirus/virología , Flavonoides/farmacología , Neumonía Viral/virología , Inhibidores de la Enzima Convertidora de Angiotensina/química , Antivirales/química , Productos Biológicos/química , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Susceptibilidad a Enfermedades , Flavonoides/química , Humanos , Estadios del Ciclo de Vida , Modelos Moleculares , Pandemias , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Vigilancia de la Población , Relación Estructura-Actividad
19.
Ann Clin Microbiol Antimicrob ; 19(1): 40, 2020 Sep 02.
Artículo en Inglés | MEDLINE | ID: covidwho-742412

RESUMEN

A novel coronavirus (SARS-CoV-2), causing an emerging coronavirus disease (COVID-19), first detected in Wuhan City, Hubei Province, China, which has taken a catastrophic turn with high toll rates in China and subsequently spreading across the globe. The rapid spread of this virus to more than 210 countries while affecting more than 25 million people and causing more than 843,000 human deaths, it has resulted in a pandemic situation in the world. The SARS-CoV-2 virus belongs to the genus Betacoronavirus, like MERS-CoV and SARS-CoV, all of which originated in bats. It is highly contagious, causing symptoms like fever, dyspnea, asthenia and pneumonia, thrombocytopenia, and the severely infected patients succumb to the disease. Coronaviruses (CoVs) among all known RNA viruses have the largest genomes ranging from 26 to 32 kb in length. Extensive research has been conducted to understand the molecular basis of the SARS-CoV-2 infection and evolution, develop effective therapeutics, antiviral drugs, and vaccines, and to design rapid and confirmatory viral diagnostics as well as adopt appropriate prevention and control strategies. To date, August 30, 2020, no effective, proven therapeutic antibodies or specific drugs, and vaccines have turned up. In this review article, we describe the underlying molecular organization and phylogenetic analysis of the coronaviruses, including the SARS-CoV-2, and recent advances in diagnosis and vaccine development in brief and focusing mainly on developing potential therapeutic options that can be explored to manage this pandemic virus infection, which would help in valid countering of COVID-19.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/prevención & control , Coronavirus/inmunología , Pandemias/prevención & control , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico , Vacunas/uso terapéutico , Betacoronavirus , China/epidemiología , Infecciones por Coronavirus/epidemiología , Humanos , Síndrome Respiratorio Agudo Grave/epidemiología
20.
Nat Commun ; 11(1): 4252, 2020 08 25.
Artículo en Inglés | MEDLINE | ID: covidwho-741685

RESUMEN

The 2019 novel respiratory virus (SARS-CoV-2) causes COVID-19 with rapid global socioeconomic disruptions and disease burden to healthcare. The COVID-19 and previous emerging virus outbreaks highlight the urgent need for broad-spectrum antivirals. Here, we show that a defensin-like peptide P9R exhibited potent antiviral activity against pH-dependent viruses that require endosomal acidification for virus infection, including the enveloped pandemic A(H1N1)pdm09 virus, avian influenza A(H7N9) virus, coronaviruses (SARS-CoV-2, MERS-CoV and SARS-CoV), and the non-enveloped rhinovirus. P9R can significantly protect mice from lethal challenge by A(H1N1)pdm09 virus and shows low possibility to cause drug-resistant virus. Mechanistic studies indicate that the antiviral activity of P9R depends on the direct binding to viruses and the inhibition of virus-host endosomal acidification, which provides a proof of concept that virus-binding alkaline peptides can broadly inhibit pH-dependent viruses. These results suggest that the dual-functional virus- and host-targeting P9R can be a promising candidate for combating pH-dependent respiratory viruses.


Asunto(s)
Antivirales/farmacología , Coronavirus/efectos de los fármacos , Virus de la Influenza A/efectos de los fármacos , Péptidos/farmacología , Secuencia de Aminoácidos , Animales , Antivirales/química , Antivirales/metabolismo , Antivirales/uso terapéutico , Línea Celular , Endosomas/química , Endosomas/efectos de los fármacos , Femenino , Humanos , Concentración de Iones de Hidrógeno , Virus de la Influenza A/metabolismo , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones por Orthomyxoviridae/metabolismo , Péptidos/química , Péptidos/metabolismo , Péptidos/uso terapéutico , Unión Proteica , Conformación Proteica , Rhinovirus/efectos de los fármacos , Rhinovirus/metabolismo , Carga Viral/efectos de los fármacos , Replicación Viral/efectos de los fármacos
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