RESUMEN
In view of the potential of traditional plant-based remedies (or phytomedicines) in the management of COVID-19, the present investigation was aimed at finding novel anti-SARS-CoV-2 molecules by in silico screening of bioactive phytochemicals (database) using computational methods and drug repurposing approach. A total of 160 compounds belonging to various phytochemical classes (flavonoids, limonoids, saponins, triterpenoids, steroids etc.) were selected (as initial hits) and screened against three specific therapeutic targets (Mpro/3CLpro, PLpro and RdRp) of SARS-CoV-2 by docking, molecular dynamics simulation and drug-likeness/ADMET studies. From our studies, six phytochemicals were identified as notable ant-SARS-CoV-2 agents (best hit molecules) with promising inhibitory effects effective against protease (Mpro and PLpro) and polymerase (RdRp) enzymes. These compounds are namely, ginsenoside Rg2, saikosaponin A, somniferine, betulinic acid, soyasapogenol C and azadirachtin A. On the basis of binding modes and dynamics studies of protein-ligand intercations, ginsenoside Rg2, saikosaponin A, somniferine were found to be the most potent (in silico) inhibitors potentially active against Mpro, PLpro and RdRp, respectively. The present investigation can be directed towards further experimental studies in order to confirm the anti-SARS-CoV-2 efficacy along with toxicities of identified phytomolecules.
RESUMEN
The significance of biomaterials is well appreciated in nanotechnology, and its use has resulted in major advances in biomedical sciences. Although, currently, very little data is available on the clinical trial studies for treatment of neurological conditions, numerous promising advancements have been reported in drug delivery and regenerative therapies which can be applied in clinical practice. Among the commonly reported biomaterials in literature, the self-assembling peptides and hydrogels have been recognized as the most potential candidate for treatment of common neurological conditions such as Alzheimer's, Parkinson's, spinal cord injury, stroke and tumors. The hydrogels, specifically, offer advantages like flexibility and porosity, and mimics the properties of the extracellular matrix of the central nervous system. These factors make them an ideal scaffold for drug delivery through the blood-brain barrier and tissue regeneration (using stem cells). Thus, the use of biomaterials as suitable matrix for therapeutic purposes has emerged as a promising area of neurosciences. In this review, we describe the application of biomaterials, and the current advances, in treatment of statistically common neurological disorders.
RESUMEN
There are regular reports of extrapulmonary infections and manifestations related to the ongoing COVID-19 pandemic. Coronaviruses are potentially neurotropic, which renders neuronal tissue vulnerable to infection, especially in elderly individuals or in those with neuro-comorbid conditions. Complaints of ageusia, anosmia, myalgia, and headache; reports of diseases such as stroke, encephalopathy, seizure, and encephalitis; and loss of consciousness in patients with COVID-19 confirm the neuropathophysiological aspect of this disease. The brain is linked to pulmonary organs, physiologically through blood circulation, and functionally through the nervous system. The interdependence of these vital organs may further aggravate the pathophysiological aspects of COVID-19. The induction of a cytokine storm in systemic circulation can trigger a neuroinflammatory cascade, which can subsequently compromise the blood-brain barrier and activate microglia- and astrocyte-borne Toll-like receptors, thereby leading to neuronal tissue damage. Hence, a holistic approach should be adopted by healthcare professionals while treating COVID-19 patients with a history of neurodegenerative disorders, neuropsychological complications, or any other neuro-compromised conditions. Imperatively, vaccines are being developed at top priority to contain the spread of the severe acute respiratory syndrome coronavirus 2, and different vaccines are at different stages of development globally. This review discusses the concerns regarding the neuronal complications of COVID-19 and the possible mechanisms of amelioration.
