scholarly journals Potential Inhibitors of SARS-CoV-2 Main Protease (Mpro) Identified from the Library of FDA Approved Drugs Using Molecular Docking Studies

2020 ◽  
Author(s):  
Dipesh Verma ◽  
Srajan Kapoor ◽  
Satyajeet Das ◽  
Krishan Thakur
Keyword(s):  
Molecular Docking ◽  
Therapeutic Potential ◽  
Docking Studies ◽  
Antiviral Compound ◽  
Molecular Docking Studies ◽  
Main Protease ◽  
Approved Drugs ◽  
Fda Approved Drugs

Corona Virus Infectious Disease-2019 (COVID-19) outbreak originated recently at Wuhan, China in December 2019. It has already spread rapidly to more than 200 countries and has been declared a pandemic by WHO. It is caused by a beta-coronavirus named as SARS-CoV-2. There is no definitive cure, either drug or vaccine, to treat or prevent this viral disease. Recently, the crystal structure of the main protease Mpro has been determined. Mpro is responsible for the proteolytic maturation of the polyprotein essential for the viral replication and transcription, which makes it an important drug target. The discovery of new drug molecules may take years before getting to the clinics. So, considering urgency we performed molecular docking studies using FDA approved drugs to identify molecules that could potentially bind to the substrate-binding site and inhibit SARS-CoV-2 main protease (Mpro). We used the Glide module in Schrodinger software suite to perform molecular docking studies followed by MM-GBSA based energy calculations to score the hit molecules. Molecular docking and manual analysis suggest that several drugs may bind and potentially inhibit Mpro. We also performed molecular simulations studies for selected compounds to evaluate protein-drug interactions. Interestingly, we observed only one antiviral compound, Adefovir, in the top50 list of compounds. Considering bioavailability, lesser toxicity, route of administration some of the top-ranked drugs including lumefantrine (antimalarial), dipyridamole (coronary vasodilator), dihydroergotamine (used for treating migraine), hexoprenaline (anti- asthmatic), riboflavin (vitamin B2) and pantethine (vitamin B5) may be taken forward for further in vitro and in vivo experiments to investigate their therapeutic potential.

scholarly journals Hypoglycemic, hepatoprotective and molecular docking studies of 5-[(4-chlorophenoxy) methyl]-1, 3, 4-oxadiazole-2-thiol

2018 ◽  
Vol 13 (2) ◽  
pp. 149 ◽  
Author(s):  
Naureen Shehzadi ◽  
Khalid Hussain ◽  
Nadeem Irfan Bukhari ◽  
Muhammad Islam ◽  
Muhammad Tanveer Khan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Video Clip ◽  
Serum Levels ◽  
Docking Studies ◽  
Normal Serum ◽  
Yeast Cells ◽  
Drug Candidate ◽  
Molecular Docking Studies

<p class="Abstract">The present study aimed at the evaluation of anti-hyperglycemic and hepatoprotective potential of a new drug candidate, 5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2-thiol (OXCPM) through in vitro and in vivo assays, respectively. The compound displayed excellent dose-dependent ɑ-amylase (28.0-92.0%), ɑ-glucosidase (40.3-93.1%) and hemoglobin glycosylation (9.0%-54.9%) inhibitory effects and promoted the uptake of glucose by the yeast cells (0.2 to 26.3%). The treatment of the isoniazid- and rifampicin- (p.o., 50 mg/kg of each) intoxicated rats with OXCPM (100 mg/kg, p.o.) resulted in restoring the normal serum levels of the non-enzymatic (total bilirubin, total protein and albumin) and bringing about a remarkable decrease in the levels of enzymatic (alanine transaminases, aspartate transaminases and alkaline phosphatase) biomarkers. The molecular docking studies indicated high binding affinity of the compound for hyperglycemia-related protein targets; fructose-1,6-bisphosphatase, beta<sub>2</sub>-adrenergic receptors and glucokinase. The results indicate that OXCPM may not only reduce hyperglycemia by enzyme inhibition but also the disease complications through protection of hemoglobin glycosylation and hepatic injury.</p><p class="Abstract"><strong>Video Clip of Methodology:</strong></p><p class="Abstract">Glucose uptake by yeast cells:   4 min 51 sec   <a href="https://www.youtube.com/v/8cJkuMtV0Wc">Full Screen</a>   <a href="https://www.youtube.com/watch?v=8cJkuMtV0Wc">Alternate</a></p>

Evaluation of anti-diabetic and alpha glucosidase inhibitory action of anthraquinones from Rheum emodi

2015 ◽  
Vol 6 (8) ◽  
pp. 2693-2700 ◽  
Author(s):  
Aditya Arvindekar ◽  
Tanaji More ◽  
Pavan V. Payghan ◽  
Kirti Laddha ◽  
Nanda Ghoshal ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Action ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Alpha Glucosidase

The 1,8-dihydroxyanthraquinones from the culinary and medicinally important plant Rheum emodi exert anti-hyperglycemic potential but notably different α-glucosidase actions as established by in vitro, in vivo, kinetics and molecular docking studies.

Potential Bioactive glycosylated flavonoids as SARS-CoV-2 Main protease Inhibitors: A molecular Docking Study

2020 ◽  
Author(s):  
sabri ahmed cherrak ◽  
merzouk hafida ◽  
mokhtari soulimane nassima
Keyword(s):  
Molecular Docking ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
In Vivo Experiments ◽  
Main Protease

A novel (COVID-19) responsible of acute respiratory infection closely related to SARS-CoV has recently emerged. So far there is no consensus for drug treatment to stop the spread of the virus. Discovery of a drug that would limit the virus expansion is one of the biggest challenges faced by the humanity in the last decades. In this perspective, testing existing drugs as inhibitors of the main COVID-19 protease is a good approach.Among natural phenolic compounds found in plants, fruit, and vegetables; flavonoids are the most abundant. Flavonoids, especially in their glycosylated forms, display a number of physiological activities, which makes them interesting to investigate as antiviral molecules.The flavonoids chemical structures were downloaded from PubChem and protease structure 6lu7 was from the Protein Data Bank site. Molecular docking study was performed using AutoDock Vina. Among the tested molecules Quercetin-3-O-rhamnoside showed the highest binding affinity (-9,7 kcal/mol). Docking studies showed that glycosylated flavonoids are good inhibitors for the covid-19 protease and could be further investigated by in vitro and in vivo experiments for further validation.

scholarly journals New Role for FDA-Approved Drugs in Combating Antibiotic-Resistant Bacteria

2016 ◽  
Vol 60 (6) ◽  
pp. 3717-3729 ◽  
Author(s):  
Jourdan A. Andersson ◽  
Eric C. Fitts ◽  
Michelle L. Kirtley ◽  
Duraisamy Ponnusamy ◽  
Alex G. Peniche ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Bacterial Pathogens ◽  
Bactericidal Effect ◽  
Resistant Bacteria ◽  
Content Type ◽  
Broad Applicability ◽  
Approved Drugs ◽  
Fda Approved Drugs

Antibiotic resistance in medically relevant bacterial pathogens, coupled with a paucity of novel antimicrobial discoveries, represents a pressing global crisis. Traditional drug discovery is an inefficient and costly process; however, systematic screening of Food and Drug Administration (FDA)-approved therapeutics for other indications in humans offers a rapid alternative approach. In this study, we screened a library of 780 FDA-approved drugs to identify molecules that rendered RAW 264.7 murine macrophages resistant to cytotoxicity induced by the highly virulentYersinia pestisCO92 strain. Of these compounds, we identified 94 not classified as antibiotics as being effective at preventingY. pestis-induced cytotoxicity. A total of 17 prioritized drugs, based on efficacy inin vitroscreens, were chosen for further evaluation in a murine model of pneumonic plague to delineate ifin vitroefficacy could be translatedin vivo. Three drugs, doxapram (DXP), amoxapine (AXPN), and trifluoperazine (TFP), increased animal survivability despite not exhibiting any direct bacteriostatic or bactericidal effect onY. pestisand having no modulating effect on crucialY. pestisvirulence factors. These findings suggested that DXP, AXPN, and TFP may modulate host cell pathways necessary for disease pathogenesis. Finally, to further assess the broad applicability of drugs identified fromin vitroscreens, the therapeutic potential of TFP, the most efficacious drugin vivo, was evaluated in murine models ofSalmonella entericaserovar Typhimurium andClostridium difficileinfections. In both models, TFP treatment resulted in increased survivability of infected animals. Taken together, these results demonstrate the broad applicability and potential use of nonantibiotic FDA-approved drugs to combat respiratory and gastrointestinal bacterial pathogens.

Feruloyl Sucrose Esters: Potent and Selective Inhibitors of α-glucosidase and α-amylase.

2021 ◽  
Vol 28 ◽  
Author(s):  
Surabhi Devaraj ◽  
Yew Mun Yip ◽  
Parthasarathi Panda ◽  
Li Lin Ong ◽  
Pooi Wen Kathy Wong ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Blood Glucose ◽  
Side Effects ◽  
Docking Studies ◽  
Sucrose Esters ◽  
Molecular Docking Studies ◽  
Gastrointestinal Side Effects ◽  
Lead Candidate

Introduction: Feruloyl Sucrose Esters (FSEs) are a class of Phenylpropanoid Sucrose Esters (PSEs) widely distributed in plants. They were investigated as potential selective Alpha Glucosidase Inhibitors (AGIs) to eliminate the side effects associated with the current commercial AGIs. The latter effectively lowers blood glucose levels in diabetic patients but causes severe gastrointestinal side effects. Methods: Systematic structure-activity relationship (SAR) studies using in silico, in vitro and in vivo experiments were used to accomplish this aim. FSEs were evaluated for their in vitro inhibition of starch and oligosaccharide digesting enzymes α-glucosidase and α-amylase followed by in silico docking studies to identify the binding modes. A lead candidate, FSE 12 was investigated in an STZ mouse model. Results: All active FSEs showed desired higher % inhibition of α-glucosidase and desired lower inhibition of α-amylase in comparison to AGI gold standard acarbose. This suggests a greater selectivity of the FSEs towards α-glucosidase than α-amylase, which is proposed to eliminate the gastrointestinal side effects. From the in vitro studies, the position and number of the feruloyl substituents on the sucrose core, the aromatic ‘OH’ group, and the diisopropylidene bridges were key determinants of the % inhibition of α-glucosidase and α-amylase. In particular, the diisopropylidene bridges are critical for achieving inhibition selectivity. Molecular docking studies of the FSEs corroborates the in vitro results. The molecular docking studies further reveal that the presence of free aromatic ‘OH’ groups and the substitution at position 3 on the sucrose core are critical for the inhibition of both the enzymes. From the in vitro and molecular docking studies, FSE 12 was selected as a lead candidate for validation in vivo. The oral co-administration of FSE 12 with starch abrogated the increase in post-prandial glucose and significantly reduced blood glucose excursion in STZ-treated mice compared to control (starch only) mice. Conclusion: Our studies reveal the potential of FSEs as selective AGIs for the treatment of diabetes, with a hypothetical reduction of side effects associated with commercial AGIs.

2-Aryl-3-(2-morpholinoethyl)thiazolidin-4-ones: Synthesis, anti-inflammatory in vivo, cytotoxicity in vitro and molecular docking studies

2016 ◽  
Vol 118 ◽  
pp. 259-265 ◽  
Author(s):  
Daniela Pires Gouvea ◽  
Flávia Aleixo Vasconcellos ◽  
Gabriele dos Anjos Berwaldt ◽  
Amilton Clair Pinto Seixas Neto ◽  
Gerferson Fischer ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Anti Inflammatory ◽  
In Vivo Cytotoxicity
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