RESUMEN
Therapeutic approaches to COVID-19 treatment require appropriate inhibitors to target crucial proteins of SARS-CoV-2 replication machinery. It's been approximately 12 months since the pandemic started, yet no known specific drugs are available. However, research progresses with time in terms of high throughput virtual screening (HTVS) and rational design of repurposed, novel synthetic and natural products discovery by understanding the viral life cycle, immuno-pathological and clinical outcomes in patients based on host's nutritional, metabolic, and lifestyle status. Further, complementary and alternative medicine (CAM) approaches have also improved resiliency and immune responses. In this article, we summarize all the therapeutic antiviral strategies for COVID-19 drug discovery including computer aided virtual screening, repurposed drugs, immunomodulators, vaccines, plasma therapy, various adjunct therapies, and phage technology to unravel insightful mechanistic pathways of targeting SARS-CoV-2 and host's intrinsic, innate immunity at multiple checkpoints that aid in the containment of the disease.
Asunto(s)
Corticoesteroides/administración & dosificación , Antivirales/administración & dosificación , Tratamiento Farmacológico de COVID-19 , Vacunas contra la COVID-19/administración & dosificación , COVID-19/inmunología , Descubrimiento de Drogas/tendencias , Animales , COVID-19/prevención & control , Descubrimiento de Drogas/métodos , Ensayos Analíticos de Alto Rendimiento/métodos , Ensayos Analíticos de Alto Rendimiento/tendencias , Humanos , Inmunidad Innata/efectos de los fármacos , Inmunidad Innata/inmunología , Interferón alfa-2/administración & dosificación , Interleucina-6/antagonistas & inhibidores , Interleucina-6/inmunologíaRESUMEN
The combination of Interferon-α-2b (IFN-α-2b) and phototherapy is highly effective in treating mycosis fungoides (MF) but side effects often lead to discontinuation of therapy.1.
Asunto(s)
Interferón alfa-2/administración & dosificación , Interferón-alfa/administración & dosificación , Micosis Fungoide/tratamiento farmacológico , Terapia PUVA/métodos , Polietilenglicoles/administración & dosificación , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Relación Dosis-Respuesta a Droga , Estudios de Factibilidad , Femenino , Humanos , Interferón alfa-2/efectos adversos , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Micosis Fungoide/diagnóstico , Estadificación de Neoplasias , Terapia PUVA/efectos adversos , Proyectos Piloto , Polietilenglicoles/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Neoplasias Cutáneas/diagnóstico , Resultado del TratamientoRESUMEN
OBJECTIVE: Vitamin K2, which is present in dairy products and has been recommended as a micronutrient supplement in humans, contains anticancer properties. Interferon (IFN)-α-2b administered during development of hepatic preneoplasia decreased both number and volume percentage of altered hepatic foci (AHF) by increasing apoptosis in the foci. The aim of this study was to evaluate the effects of IFN-α-2b treatment supplemented with vitamin K2 in the early stages of liver cancer development in rats. METHODS: Adult male Wistar rats were subjected to a two-phase model of hepatocarcinogenesis (initiated-promoted [IP] group). Animals were divided into four groups: untreated (IP), IP treated with IFN-α-2b (6.5â¯×â¯105 U/kg), IP treated with vitamin K2 (10 mg/kg), and IP treated with both compounds. RESULTS: The study results demonstrated that vitamin K2 blocked IFN-α-2b-induced reduction in size and volume of the altered hepatic foci and inhibited IFN-α-2b-induced apoptosis. Its inhibition of IFN-α-2b-induced apoptosis was mediated by increased levels of total hepatic Bcl-2 in rat preneoplastic livers. CONCLUSION: These findings demonstrate that supportive vitamin supplements or therapies are not always safe because they could put the life of patients treated with IFN-α-2b at risk.
Asunto(s)
Antineoplásicos/administración & dosificación , Carcinogénesis/efectos de los fármacos , Suplementos Dietéticos , Interferón alfa-2/administración & dosificación , Vitamina K 2/administración & dosificación , Vitaminas/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Hígado/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Lesiones Precancerosas/tratamiento farmacológico , Ratas , Ratas WistarRESUMEN
BACKGROUND AND OBJECTIVE: Corneal neovascularization (CNV) is a vision-threatening condition arising from various corneal diseases. The aim of this study is to compare the effectiveness of bevacizumab and interferon alpha-2a (IFNα-2a) treatment on corneal neovascularization. MATERIALS AND METHODS: Twenty-four Wistar albino rats were used in this study. After cauterization of the cornea with a silver nitrate applicator stick, the control group received 0.1 mL saline solution, the second group received 0.1 mL IFNα-2a (IFNα-2a, 6 million international units [MIU]/0.5 mL), and the third group received 2.5 mg bevacizumab by subconjunctival injection. An additional injection was administered to each group on the fourth day. After one week, the corneal neovascularization rate and the longest neovascular sprout length were determined. RESULTS: The neovascularization rate (saline 0.65 ± 0.05; IFNα-2a 0.62 ± 0.07; bevacizumab 0.42 ± 0.11) with bevacizumab was significantly lower, more than those with IFNα-2a and saline (p < 0.001 and p < 0.001). The longest neovascular sprout length (saline, 4.00 ± 0.6 mm; IFNα-2a, 3.63 ± 0.52 mm; bevacizumab, 2.81 ± 0.65 mm) with bevacizumab was significantly shorter than those with saline and IFNα-2a (p = 0.001 and p = 0.012). CONCLUSIONS: Subconjunctival IFNα-2a has limited efficacy in the treatment of corneal neovascularization.