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1.
AAPS PharmSciTech ; 22(5): 173, 2021 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-34105037

RESUMEN

Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.


Asunto(s)
Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/fisiopatología , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Animales , Antivirales/administración & dosificación , Antivirales/inmunología , Camelus/virología , Quirópteros/virología , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/transmisión , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/efectos de los fármacos , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Arabia Saudita/epidemiología , Zoonosis Virales/epidemiología , Zoonosis Virales/inmunología , Zoonosis Virales/transmisión
2.
Bioengineered ; 12(1): 2274-2287, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34077310

RESUMEN

Xuebijing Injection have been found to improve the clinical symptoms of COVID-19 and alleviate disease severity, but the mechanisms are currently unclear. This study aimed to investigate the potential molecular targets and mechanisms of the Xuebijing injection in treating COVID-19 via network pharmacology and molecular docking analysis. The main active ingredients and therapeutic targets of the Xuebijing injection, and the pathogenic targets of COVID-19 were screened using the TCMSP, UniProt, and GeneCard databases. According to the 'Drug-Ingredients-Targets-Disease' network built by STRING and Cytoscape, AKT1 was identified as the core target, and baicalein, luteolin, and quercetin were identified as the active ingredients of the Xuebijing injection in connection with AKT1. R language was used for enrichment analysis that predict the mechanisms by which the Xuebijing injection may inhibit lipopolysaccharide-mediated inflammatory response, modulate NOS activity, and regulate the TNF signal pathway by affecting the role of AKT1. Based on the results of network pharmacology, a molecular docking was performed with AKT1 and the three active ingredients, the results indicated that all three active ingredients could stably bind with AKT1. These findings identify potential molecular mechanisms by which Xuebijing Injection inhibit COVID-19 by acting on AKT1.


Asunto(s)
Antivirales/administración & dosificación , COVID-19/tratamiento farmacológico , COVID-19/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , SARS-CoV-2 , Antivirales/farmacocinética , Antivirales/farmacología , Ingeniería Biomédica , Medicamentos Herbarios Chinos/farmacocinética , Medicamentos Herbarios Chinos/farmacología , Flavanonas/administración & dosificación , Humanos , Inyecciones , Luteolina/administración & dosificación , Simulación del Acoplamiento Molecular , Pandemias , Unión Proteica , Mapas de Interacción de Proteínas , Proteínas Proto-Oncogénicas c-akt/química , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Quercetina/administración & dosificación , Transducción de Señal/efectos de los fármacos
3.
AAPS PharmSciTech ; 22(5): 181, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-34129154

RESUMEN

In this study, two hydrophilic polymers hydroxypropyl methyl cellulose and beta-cyclodextrin (ß-CD) are used to synthesize highly responsive and spongy polymeric matrices. Porous and stimulus-responsive polymeric network was developed to improve the solubility of acyclovir (ACV) at significant level. Grafting was successfully carried out by free radical polymerization technique. Spongy matrices were characterized by percentage entrapment efficiency, drug loading, solubility studies, FTIR, powder X-ray diffraction, TGA, DSC, XRD, SEM, swelling studies, and in vitro studies. Acute oral toxicity studies were conducted to determine the safety of oral administration of prepared HPMC-ßCD-g-poly(AMPS) formulation. Porous and spongy structures were depicted in SEM images. Complex formation and thermal stability of constituents and drug (ACV) were analyzed by FTIR, TGA, and DSC spectra. XRD analysis revealed reduction in acyclovir crystallinity in spongy matrices. Particle size of optimized formulation was found in the range of 197 ± 2.55 nm. The momentous difference with reference product committed that drug solubility and release characteristics were markedly enhanced by the developed spongy matrices. Toxicity studies endorsed that developed spongy matrices were non-toxic and compatible to biological system. The efficient method of preparation, enhanced solubility, excellent physico-chemical characteristics, high dissolution, and non-toxic HPMC-ßCD-g-poly(AMPS) spongy matrices may be a promising approach for oral delivery of poorly soluble drugs.


Asunto(s)
Acrilamidas/síntesis química , Aciclovir/síntesis química , Alcanosulfonatos/síntesis química , Derivados de la Hipromelosa/síntesis química , Polimerizacion , beta-Ciclodextrinas/síntesis química , Acrilamidas/administración & dosificación , Aciclovir/administración & dosificación , Administración Oral , Alcanosulfonatos/administración & dosificación , Animales , Antivirales/administración & dosificación , Antivirales/síntesis química , Evaluación Preclínica de Medicamentos/métodos , Derivados de la Hipromelosa/administración & dosificación , Masculino , Tamaño de la Partícula , Polímeros/administración & dosificación , Polímeros/síntesis química , Conejos , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Difracción de Rayos X/métodos , beta-Ciclodextrinas/administración & dosificación
4.
Mayo Clin Proc ; 96(5): 1250-1261, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33958056

RESUMEN

The administration of spike monoclonal antibody treatment to patients with mild to moderate COVID-19 is very challenging. This article summarizes essential components and processes in establishing an effective spike monoclonal antibody infusion program. Rapid identification of a dedicated physical infrastructure was essential to circumvent the logistical challenges of caring for infectious patients while maintaining compliance with regulations and ensuring the safety of our personnel and other patients. Our partnerships and collaborations among multiple different specialties and disciplines enabled contributions from personnel with specific expertise in medicine, nursing, pharmacy, infection prevention and control, electronic health record (EHR) informatics, compliance, legal, medical ethics, engineering, administration, and other critical areas. Clear communication and a culture in which all roles are welcomed at the planning and operational tables are critical to the rapid development and refinement needed to adapt and thrive in providing this time-sensitive beneficial therapy. Our partnerships with leaders and providers outside our institutions, including those who care for underserved populations, have promoted equity in the access of monoclonal antibodies in our regions. Strong support from institutional leadership facilitated expedited action when needed, from a physical, personnel, and system infrastructure standpoint. Our ongoing real-time assessment and monitoring of our clinical program allowed us to improve and optimize our processes to ensure that the needs of our patients with COVID-19 in the outpatient setting are met.


Asunto(s)
Antivirales/administración & dosificación , COVID-19 , Vías Clínicas , Terapia de Infusión a Domicilio , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Anticuerpos Monoclonales/administración & dosificación , COVID-19/epidemiología , COVID-19/terapia , Protocolos Clínicos , Vías Clínicas/organización & administración , Vías Clínicas/tendencias , Eficiencia Organizacional , Terapia de Infusión a Domicilio/métodos , Terapia de Infusión a Domicilio/normas , Humanos , Colaboración Intersectorial , Cultura Organizacional , Desarrollo de Programa/métodos , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores , Glicoproteína de la Espiga del Coronavirus/inmunología , Estados Unidos/epidemiología
5.
Medicine (Baltimore) ; 100(21): e26059, 2021 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-34032734

RESUMEN

BACKGROUND: : Coronavirus disease 2019 (COVID-19) is an emerging and rapidly evolving disease, with no recommended effective anti-coronavirus treatments. Traditional Chinese Medicine (TCM) has been widely used to treat COVID-19 in China, and the most used one is Lianhuaqingwen (LH). This study aimed to assess the efficacy and safety of LH combined with usual treatment vs usual treatment alone in treating mild or moderate COVID-19 by a meta-analysis of randomized controlled trials (RCTs). METHODS AND ANALYSIS: : We systematically searched the Medline (OVID), Embase, the Cochrane Library, and 4 Chinese databases from inception to July 2020 to include the RCTs that evaluated the efficacy and safety of LH in combination with usual treatment vs usual treatment for mild or moderate COVID-19. A meta-analysis was performed to calculate the risk ratio (RR) and 95% confidence interval (CI) for binary outcomes and mean difference (MD) for continuous outcomes. RESULTS: : A total of 5 RCTs with 824 individuals with mild or moderate COVID 19 were included. Compared with the usual treatment alone, LH in combination with usual treatment significantly improved the overall clinical efficacy (RR = 2.39, 95% CI 1.61-3.55), increased the rate of recovery of chest computed tomographic manifestations (RR = 1.80, 95% CI 1.08-3.01), reduced the rate of conversion to severe cases (RR = 0.47, 95% CI 0.29-0.74), shorten the duration of fever (MD = -1.00, 95% CI -1.17 to -0.84). Moreover, LH in combination with usual treatment did not increase the occurrence of the adverse event compared to usual treatment alone. CONCLUSION: : Our meta-analysis of RCTs indicated that LH in combination with usual treatment may improve the clinical efficacy in patients with mild or moderate COVID-19 without increasing adverse events. However, given the limitations and poor quality of included trials in this study, further large-sample RCTs or high-quality real-world studies are needed to confirm our conclusions.


Asunto(s)
Antivirales/administración & dosificación , COVID-19/terapia , Medicamentos Herbarios Chinos/administración & dosificación , Oxígeno/administración & dosificación , Antivirales/efectos adversos , COVID-19/diagnóstico , COVID-19/virología , China , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Pulmón/diagnóstico por imagen , Apoyo Nutricional , Oxígeno/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
6.
Artículo en Inglés | MEDLINE | ID: mdl-34052564

RESUMEN

Favipiravir is a broad-spectrum inhibitor of viral RNA polymerase. It is currently used as a possible treatment for coronavirus disease 2019 (COVID-19). Pre-clinical or clinical trials of favipiravir require robust, sensitive, and accurate bioanalytical methods for quantitation of favipiravir levels. Recently, several studies have been reported about developing a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring favipiravir levels. However, these methods were validated predominantly for plasma samples, electrospray ionization was operated only in negative or positive mode, and clinical application of these methods has not been applied for patients with COVID-19. This study aimed was to develop a validated LC-MS/MS method for the measurement of favipiravir levels in positive and negative electrospray ionization mode and to perform a pilot study in patients with COVID-19 receiving favipiravir to demonstrate the applicability of this method in biological samples. Simple protein precipitation was used for the extraction of favipiravir from the desired matrix. Favipiravir levels were quantitated using MS / MS with an electrospray ionization source in positive and negative multiple reaction monitoring (MRM) mode. The chromatographic detection was performed on a reverse-phase Phenomenex C18 column (50 mm × 4.6 mm, 5 µm, 100 Å) with gradient elution using 0.1% formic acid in water and 0.1% formic acid in methanol as mobile phase. The method was linear over the concentration ranges of 0.048-50 µg/mL (in negative ionization mode) and 0.062-50 µg/mL (in positive ionization mode) with a correlation coefficient (r2) better than 0.998. The total run time was 3.5 min. The intra-assay and inter-assay %CV values were less than 7.2% and 8.0%, respectively. A simple, rapid and robust LC-MS / MS method was developed for the measurement of favipiravir and validation studies were performed. The validated method was successfully applied for drug level measurement in COVID-19 patients receiving favipiravir.


Asunto(s)
Amidas/sangre , COVID-19/tratamiento farmacológico , Cromatografía Liquida/métodos , Pirazinas/sangre , Espectrometría de Masas en Tándem/métodos , Amidas/administración & dosificación , Amidas/uso terapéutico , Antivirales/administración & dosificación , Antivirales/sangre , Antivirales/uso terapéutico , COVID-19/sangre , Estabilidad de Medicamentos , Humanos , Límite de Detección , Pirazinas/administración & dosificación , Pirazinas/uso terapéutico , Sensibilidad y Especificidad , Espectrometría de Masa por Ionización de Electrospray/métodos
7.
Life Sci ; 278: 119580, 2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-33991549

RESUMEN

COVID-19 pandemic is still a major risk to human civilization. Besides the global immunization policy, more than five lac new cases are documented everyday. Some countries newly implement partial/complete nationwid lockdown to mitigate recurrent community spreading. To avoid the new modified stain of SARS-CoV-2 spreading, some countries imposed any restriction on the movement of the citizens within or outside the country. Effective economical point of care diagnostic and therapeutic strategy is vigorously required to mitigate viral spread. Besides struggling with repurposed medicines, new engineered materials with multiple unique efficacies and specific antiviral potency against SARS-CoV-2 infection may be fruitful to save more lives. Nanotechnology-based engineering strategy sophisticated medicine with specific, effective and nonhazardous delivery mechanism for available repurposed antivirals as well as remedial for associated diseases due to malfeasance in immuno-system e.g. hypercytokinaemia, acute respiratory distress syndrome. This review will talk about gloomy but critical areas for nanoscientists to intervene and will showcase about the different laboratory diagnostic, prognostic strategies and their mode of actions. In addition, we speak about SARS-CoV-2 pathophysiology, pathogenicity and host specific interation with special emphasis on altered immuno-system and also perceptualized, copious ways to design prophylactic nanomedicines and next-generation vaccines based on recent findings.


Asunto(s)
COVID-19/terapia , Nanomedicina Teranóstica/métodos , Animales , Antivirales/administración & dosificación , Antivirales/uso terapéutico , COVID-19/diagnóstico , COVID-19/inmunología , COVID-19/patología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Humanos , Inmunización/métodos , Nanotecnología/métodos , Medicina de Precisión/métodos , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación
8.
Bull Math Biol ; 83(7): 79, 2021 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-34037874

RESUMEN

The pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has quickly spread worldwide, creating a serious health crisis. The virus is primarily associated with flu-like symptoms but can also lead to severe pathologies and death. We here present an ordinary differential equation model of the intrahost immune response to SARS-CoV-2 infection, fitted to experimental data gleaned from rhesus macaques. The model is calibrated to data from a nonlethal infection, but the model can replicate behavior from various lethal scenarios as well. We evaluate the sensitivity of the model to biologically relevant parameters governing the strength and efficacy of the immune response. We also simulate the effect of both anti-inflammatory and antiviral drugs on the host immune response and demonstrate the ability of the model to lessen the severity of a formerly lethal infection with the addition of the appropriately calibrated drug. Our model emphasizes the importance of tight control of the innate immune response for host survival and viral clearance.


Asunto(s)
COVID-19/inmunología , Inmunidad Innata , Macaca mulatta/inmunología , Modelos Inmunológicos , SARS-CoV-2 , Inmunidad Adaptativa , Envejecimiento/inmunología , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Antivirales/administración & dosificación , Antivirales/farmacología , COVID-19/tratamiento farmacológico , COVID-19/epidemiología , Simulación por Computador , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Interacciones Microbiota-Huesped/efectos de los fármacos , Interacciones Microbiota-Huesped/inmunología , Humanos , Conceptos Matemáticos , Pandemias , Sistema Respiratorio/inmunología , Sistema Respiratorio/virología , SARS-CoV-2/inmunología , Carga Viral/inmunología
9.
J Pharm Pharm Sci ; 24: 210-219, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33939951

RESUMEN

PURPOSE: The purpose of this study was to compare how treatment with convalescent plasma (CP) monotherapy, remdesivir (RDV) monotherapy, and combination therapy (CP + RDV) in patients with COVID-19 affected clinical outcomes. METHODS: Patients with COVID-19 infection who were admitted to the hospital received CP, RDV, or combination of both. Mortality, discharge disposition, hospital length of stay (LOS), intensive care unit (ICU) LOS, and total ventilation days were compared between each treatment group and stratified by ABO blood group. An exploratory analysis identified risk factors for mortality. Adverse effects were also evaluated. RESULTS: RDV monotherapy showed an increased chance of survival compared to combination therapy or CP monotherapy (p = 0.052). There were 15, 3, and 6 deaths in the CP, RDV, and combination therapy groups, respectively. The combination therapy group had the longest median ICU LOS (8, IQR 4.5-15.5, p = 0.220) and hospital LOS (11, IQR 7-15.5, p = 0.175). Age (p = 0.036), initial SOFA score (p = 0.013), and intubation (p = 0.005) were statistically significant predictors of mortality. Patients with type O blood had decreased ventilation days, ICU LOS, and total LOS. Thirteen treatment-related adverse events occurred. CONCLUSION: No significant differences in clinical outcomes were observed between patients treated with RDV, CP, or combination therapy. Elderly patients, those with a high initial SOFA score, and those who require intubation are at increased risk of mortality associated with COVID-19. Blood type did not affect clinical outcomes.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/administración & dosificación , COVID-19/terapia , Hospitales Comunitarios/tendencias , Adenosina Monofosfato/administración & dosificación , Adulto , Anciano , Alanina/administración & dosificación , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/mortalidad , California/epidemiología , Terapia Combinada/métodos , Femenino , Humanos , Inmunización Pasiva/mortalidad , Tiempo de Internación/tendencias , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
10.
Pan Afr Med J ; 38: 225, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34046130

RESUMEN

Liver damage during COVID-19 disease has been described in numerous studies. Its mechanism is poorly understood. It is mainly reserved for severe forms and is manifested by abnormalities of the hepatic assessment and more particularly cytolysis. Particular attention must be paid to patients with chronic liver disease, both in terms of follow-up and treatment. We wanted to know the evolution of COVID-19 and its treatment, on the liver function of a 27-year-old patient followed for chronic non-cirrhotic hepatitis B at the Hassan II University Hospital in Fez. Our patient had stopped the antiviral B treatment and presented COVID-19 infection with minimal to moderate impairment. The initial evaluation showed cytolysis at 4 times upper limit of normal (ULN). Management consisted in the immediate resumption of Tenofovir in combination with hydroxychloroquine (HCQ) and azythromycin with good clinical and biological evolution.


Asunto(s)
Antivirales/administración & dosificación , COVID-19/complicaciones , Hepatitis B Crónica/fisiopatología , Adulto , Azitromicina/administración & dosificación , COVID-19/diagnóstico , COVID-19/tratamiento farmacológico , Hepatitis B Crónica/tratamiento farmacológico , Hospitales Universitarios , Humanos , Hidroxicloroquina/administración & dosificación , Pruebas de Función Hepática , Masculino , Marruecos , Tenofovir/administración & dosificación
11.
Isr Med Assoc J ; 23(5): 318-322, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34024050

RESUMEN

BACKGROUND: The incidence of congenital cytomegalovirus (CMV) infection in Israel is 0.7%. Only 10-15% are symptomatic. Valganciclovir has been shown to improve hearing and neurodevelopmental outcomes in neonates with symptomatic congenital CMV infection. Targeted examination of infants who fail routine neonatal hearing screening or have clinical or laboratory findings suggestive of symptomatic congenital CMV infection may be a cost-effective approach. OBJECTIVES: To assess the possibility of targeted examination for the detection of newborns with symptomatic congenital CMV infection. METHODS: A prospective observational study was conducted in 2014-2015 at two medical centers in northern Israel. Included were all newborns who were tested in the first 3 days of life by polymerase chain reaction (PCR) for urine CMV DNA (n=692), either for failure the hearing screening (n=539, 78%), clinical or laboratory findings suggestive of symptomatic congenital CMV infection, or primary CMV infection during pregnancy (n=153, 22%). RESULTS: During the study period 15,433 newborns were born. The predicted rate of infection was 10-15% (symptomatic) of 0.7% of newborns, namely 0.07-0.105% or 10-15 infants. In fact, 15 infants (0.11%, 95% confidence interval 0.066-0.175) were diagnosed with symptomatic congenital CMV infection, 2/539 (0.37%) in the failed hearing group and 13/153 (8%) in the clinical/laboratory findings group. The incidence of symptomatic congenital CMV infection was within the predicted range. CONCLUSIONS: Targeted examination of only 4.5% (n=692) of newborns detected the predicted number of infants with symptomatic congenital CMV infection in whom valganciclovir therapy is recommended.


Asunto(s)
Infecciones por Citomegalovirus/diagnóstico , Pérdida Auditiva Sensorineural/diagnóstico , Tamizaje Neonatal/métodos , Reacción en Cadena de la Polimerasa , Antivirales/administración & dosificación , Infecciones por Citomegalovirus/congénito , Infecciones por Citomegalovirus/tratamiento farmacológico , ADN Viral/orina , Femenino , Pérdida Auditiva Sensorineural/virología , Humanos , Incidencia , Recién Nacido , Israel , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Estudios Prospectivos , Valganciclovir/administración & dosificación
14.
J Med Invest ; 68(1.2): 192-195, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33994470

RESUMEN

This report presents a case of a 74-year-old man who showed dramatic therapeutic response to treatment of coronavirus infectious disease-19 (COVID-19) pneumonia. He reported four-day history of sustained fever and acute progressive dyspnea. He developed severe respiratory failure, underwent urgent endotracheal intubation and showed marked elevation of inflammatory and coagulation markers such as c-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH) and D-dimer. Chest computed tomography (CT) demonstrated diffuse consolidation and ground glass opacity (GGO). We diagnosed critical COVID-19 pneumonia with detailed sick contact history and naso-pharyngeal swab of a reverse-transcriptase-polymerase-chain reaction (RT-PCR) assay testing. He received anti-viral drug, anti-interleukin (IL-6) receptor antagonist and intravenous methylprednisolone. After commencing combined intensive therapy, he showed dramatic improvement of clinical condition, serum biomarkers and radiological findings. Early diagnosis and rapid critical care management may provide meaningful clinical benefit even if severe case. J. Med. Invest. 68 : 192-195, February, 2021.


Asunto(s)
COVID-19/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , SARS-CoV-2 , Anciano , Amidas/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antivirales/administración & dosificación , COVID-19/diagnóstico por imagen , Enfermedad Crítica , Quimioterapia Combinada , Glucocorticoides/administración & dosificación , Humanos , Pulmón/diagnóstico por imagen , Masculino , Metilprednisolona/administración & dosificación , Neumonía Viral/diagnóstico por imagen , Pirazinas/administración & dosificación , Receptores de Interleucina-6/antagonistas & inhibidores , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
16.
Viruses ; 13(3)2021 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-33807592

RESUMEN

The treatment of coronavirus disease 2019 (COVID-19) has been a challenge. The efficacy of several drugs has been evaluated and variability in drug response has been observed. Pharmacogenetics could explain this variation and improve patients' outcomes with this complex disease; nevertheless, several disease-related issues must be carefully reviewed in the pharmacogenetic study of COVID-19 treatment. We aimed to describe the pharmacogenetic variants reported for drugs used for COVID-19 treatment (remdesivir, oseltamivir, lopinavir, ritonavir, azithromycin, chloroquine, hydroxychloroquine, ivermectin, and dexamethasone). In addition, other factors relevant to the design of pharmacogenetic studies were mentioned. Variants in CYP3A4, CYP3A5, CYP2C8, CY2D6, ABCB1, ABCC2, and SLCO1B1, among other variants, could be included in pharmacogenetic studies of COVID-19 treatment. Besides, nongenetic factors such as drug-drug interactions and inflammation should be considered in the search for personalized therapy of COVID-19.


Asunto(s)
Antivirales/administración & dosificación , COVID-19/tratamiento farmacológico , COVID-19/genética , SARS-CoV-2/efectos de los fármacos , Animales , COVID-19/virología , Humanos , Farmacogenética , Variantes Farmacogenómicas , SARS-CoV-2/genética , SARS-CoV-2/fisiología
17.
Nanoscale ; 13(13): 6410-6416, 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33885522

RESUMEN

The control of COVID-19 across the world requires the formation of a range of interventions including vaccines to elicit an immune response and immunomodulatory or antiviral therapeutics. Here, we demonstrate the nanoparticle formulation of a highly insoluble drug compound, niclosamide, with known anti SARS-CoV-2 activity as a cheap and scalable long-acting injectable antiviral candidate.


Asunto(s)
Antivirales , COVID-19/tratamiento farmacológico , Niclosamida , SARS-CoV-2/efectos de los fármacos , Antivirales/administración & dosificación , Antivirales/farmacología , Humanos , Inyecciones Intramusculares , Nanopartículas , Niclosamida/administración & dosificación , Niclosamida/farmacología
19.
Pan Afr Med J ; 38: 137, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33912307

RESUMEN

The treatment of chronic hepatitis C virus (HCV) infection in chronic hemodialysis patients remains an issue of great concern for nephrologists. In 2008 the kidney disease improving global outcomes working group suggested the use of pegylated interferon in end stage kidney disease patients treated by dialysis. Since then, series and some clinical trials on different direct-acting antiviral agents have shown better efficacy and tolerance than interferon-based regimens. Data on the efficacy, tolerance and the right dose of sofosbuvir in this population are still unclear. We report a case of chronic HCV genotype 1b infection in a 47-year-old patient on maintenance hemodialysis successfully treated by a combination of sofosbuvir and ledipasvir for 12 weeks. Evolution was marked by the complete regression of the hepatic cytolysis, a complete and sustained virologic response with HCV viral load undetectable for a 24 months follow-up period. No adverse reaction was found. The treatment of HCV genotype 1 or 4 infection in patients on maintenance hemodialysis is possible with sofosbuvir based regimens with a good efficacy/safety ratio in the absence of current recommended drugs for patients with eGFR<30ml/min/1.73m2. The prescription of sofosbuvir should be encouraged amongst this population in this setting.


Asunto(s)
Antivirales/administración & dosificación , Bencimidazoles/administración & dosificación , Fluorenos/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Diálisis Renal , Sofosbuvir/administración & dosificación , Antivirales/efectos adversos , Bencimidazoles/efectos adversos , Fluorenos/efectos adversos , Estudios de Seguimiento , Genotipo , Tasa de Filtración Glomerular , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/virología , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Sofosbuvir/efectos adversos , Respuesta Virológica Sostenida
20.
Nat Commun ; 12(1): 2295, 2021 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-33863887

RESUMEN

The COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use following high-risk exposure would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we show that MK-4482, an orally administered nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of MK-4482 on SARS-CoV-2 replication is observed in animals when the drug is administered either beginning 12 h before or 12 h following infection in a high-risk exposure model. These data support the potential utility of MK-4482 to control SARS-CoV-2 infection in humans following high-risk exposure as well as for treatment of COVID-19 patients.


Asunto(s)
Antivirales/administración & dosificación , COVID-19/tratamiento farmacológico , Citidina/análogos & derivados , Hidroxilaminas/administración & dosificación , SARS-CoV-2/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Administración Oral , Animales , COVID-19/virología , Chlorocebus aethiops , Citidina/administración & dosificación , Modelos Animales de Enfermedad , Humanos , Mesocricetus , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/fisiología , Células Vero
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