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Front Aging Neurosci ; 14: 878276, 2022.
Article in English | MEDLINE | ID: covidwho-2002497


Alzheimer's disease (AD) is a severe neurodegenerative disorder of the brain that manifests as dementia, disorientation, difficulty in speech, and progressive cognitive and behavioral impairment. The emerging therapeutic approach to AD management is the inhibition of ß-site APP cleaving enzyme-1 (BACE1), known to be one of the two aspartyl proteases that cleave ß-amyloid precursor protein (APP). Studies confirmed the association of high BACE1 activity with the proficiency in the formation of ß-amyloid-containing neurotic plaques, the characteristics of AD. Only a few FDA-approved BACE1 inhibitors are available in the market, but their adverse off-target effects limit their usage. In this paper, we have used both ligand-based and target-based approaches for drug design. The QSAR study entails creating a multivariate GA-MLR (Genetic Algorithm-Multilinear Regression) model using 552 molecules with acceptable statistical performance (R 2 = 0.82, Q 2 loo = 0.81). According to the QSAR study, the activity has a strong link with various atoms such as aromatic carbons and ring Sulfur, acceptor atoms, sp2-hybridized oxygen, etc. Following that, a database of 26,467 food compounds was primarily used for QSAR-based virtual screening accompanied by the application of the Lipinski rule of five; the elimination of duplicates, salts, and metal derivatives resulted in a truncated dataset of 8,453 molecules. The molecular descriptor was calculated and a well-validated 6-parametric version of the QSAR model was used to predict the bioactivity of the 8,453 food compounds. Following this, the food compounds whose predicted activity (pKi) was observed above 7.0 M were further docked into the BACE1 receptor which gave rise to the Identification of 4-(3,4-Dihydroxyphenyl)-2-hydroxy-1H-phenalen-1-one (PubChem I.D: 4468; Food I.D: FDB017657) as a hit molecule (Binding Affinity = -8.9 kcal/mol, pKi = 7.97 nM, Ki = 10.715 M). Furthermore, molecular dynamics simulation for 150 ns and molecular mechanics generalized born and surface area (MMGBSA) study aided in identifying structural motifs involved in interactions with the BACE1 enzyme. Molecular docking and QSAR yielded complementary and congruent results. The validated analyses can be used to improve a drug/lead candidate's inhibitory efficacy against the BACE1. Thus, our approach is expected to widen the field of study of repurposing nutraceuticals into neuroprotective as well as anti-cancer and anti-viral therapeutic interventions.

Environ Sci Pollut Res Int ; 29(34): 51384-51397, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1864443


COVID-19 has become one of the few leading causes of death and has evolved into a pandemic that disrupts everyone's routine, and balanced way of life worldwide, and will continue to do so. To bring an end to this pandemic, scientists had put their all effort into discovering the vaccine for SARS-CoV-2 infection. For their dedication, now, we have a handful of COVID-19 vaccines. Worldwide, millions of people are at risk due to the current pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Despite the lack of clinically authorized antiviral medications and vaccines for COVID-19, clinical trials of many recognized antiviral agents, their combination, and vaccine development in patients with confirmed COVID-19 are still ongoing. This discovery gave us a chance to get immune to this disease worldwide and end the pandemic. However, the unexpected capacity of mutation of the SARS-CoV-2 virus makes it difficult, like the recent SAS-CoV-2 Omicron variant. Therefore, there is a great necessity to spread the vaccination programs and prevent the spread of this dreadful epidemic by identifying and isolating afflicted patients. Furthermore, several COVID-19 tests are thought to be expensive, time-consuming, and require the use of adequately qualified persons to be carried out efficiently. In addition, we also conversed about how the various COVID-19 testing methods can be implemented for the first time in a developing country and their cost-effectiveness, accuracy, human resources requirements, and laboratory facilities.

COVID-19 , Antiviral Agents , COVID-19 Testing , COVID-19 Vaccines , Developing Countries , Humans , SARS-CoV-2