RESUMEN
Most recently, an outbreak of severe pneumonia caused by the infection of SARS-CoV-2, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Therefore, the role and inhibition of nsp12 are indispensable. A cryo-EM structure of RdRp from SARs-CoV-2 was used to identify novel drugs from Northern South African medicinal compounds database (NANPDB) by using computational virtual screening and molecular docking approaches. Considering Remdesivir as the control, 42 compounds were shortlisted to have docking score better than Remdesivir. The top 5 hits were validated by using molecular dynamics simulation approach and free energy calculations possess strong inhibitory properties than the Remdesivir. Thus, this study paved a way for designing novel drugs by decoding the architecture of an important enzyme and its inhibition with compounds from natural resources. This disclosing of necessary knowledge regarding the screening and the identification of top hits could help to design effective therapeutic candidates against the coronaviruses and design robust preventive measurements.
Asunto(s)
Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , Betacoronavirus/enzimología , Productos Biológicos/farmacología , Infecciones por Coronavirus/virología , Neumonía Viral/virología , ARN Polimerasa Dependiente del ARN/antagonistas & inhibidores , Proteínas no Estructurales Virales/antagonistas & inhibidores , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/química , Adenosina Monofosfato/farmacología , Alanina/análogos & derivados , Alanina/química , Alanina/farmacología , Antivirales/química , Betacoronavirus/genética , Productos Biológicos/química , COVID-19 , Dominio Catalítico/genética , Simulación por Computador , Infecciones por Coronavirus/epidemiología , ARN Polimerasa Dependiente de ARN de Coronavirus , Bases de Datos Farmacéuticas , Evaluación Preclínica de Medicamentos , Genoma Viral , Interacciones Microbiota-Huesped/efectos de los fármacos , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Pandemias , Filogenia , Neumonía Viral/epidemiología , ARN Polimerasa Dependiente del ARN/química , ARN Polimerasa Dependiente del ARN/genética , SARS-CoV-2 , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/genéticaRESUMEN
This research study evaluated the effect of different additives on the bait consumption by Indian crested porcupine, a serious forest and agricultural pest, under field conditions. Different additives (saccharin, common salt, bone meal, fish meal, peanut butter, egg yolk, egg shell powder, yeast powder, mineral oil and coconut oil) at 2 and 5% each were tested for their relative preference, using groundnut-maize (1:1) as basic bait. All the additives were tested under a no-choice test pattern. For control tests, no additive was mixed with the basic bait. Saccharin at 5% concentration significantly enhanced the consumption of bait over the basic bait, while 2% saccharin supplemented bait resulted in a non-significant bait consumption. All other additives did not enhance the consumption of the bait material; rather, these worked as repellents. However, the repellency was lowest with the common salt, followed by egg yolk, egg shell powder, bone meal, peanut butter, mineral oil, fish meal and yeast powder, while coconut remained the most repellent compound. The present study suggested that groundnut-maize (1:1) supplemented with 5% saccharin was the preferred bait combination, and can be used with different rodenticides for the management of Indian crested porcupine.