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1.
Saudi J Biol Sci ; 29(12): 103458, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2042137

ABSTRACT

COVID-19 is a progressing pandemic of coronavirus disease-2019, which had drowned the whole world in a deep sorrow sea. Uncountable deaths were extending the list of deaths every single day. The present research was aimed to study the multi-target interaction of coumarins against COVID-19 using molecular docking analysis. The structure of coumarin compounds was checked for ADME and Lipinski rule of five by using SwissADME, an online tool. SARS-CoV-2 proteins such as RdRp, PLpro, Mpro and spike protein were collected from the Protein Data Bank. The molecular docking study was performed in the PyRx tool, and the molecular interactions were visualised by Discovery Studio Visualizer. All the coumarin compounds used in the study were obeyed Lipinski's rule of 5 without any violations. All the three designed derivatives of phenprocoumon, hymecromone, and psoralen were showed high binding affinity and prominent interactions with the drug target. The presence of -OH groups in the compound, His41, a catalytic dyad in Mpro, number of and the distance of hydrogen bond interactions with SARS-CoV-2 targets was accountable for the high binding attractions. The modified drug structures possess better binding efficacy towards at least three targets compared to their parent compounds. Further, molecular dynamic studies can be suggested to find the ligand-protein complex stability. The present study outcome reveals that the designed coumarins can be synthesised and examined as a potent inhibitory drug of SARS-CoV-2.

2.
Nat Prod Res ; : 1-7, 2022 Aug 12.
Article in English | MEDLINE | ID: covidwho-1991944

ABSTRACT

Infectious diseases caused by viruses like HIV and SARS-COV-2 (COVID-19) pose serious public health threats. In search for new antiviral small molecules from chemically underexplored Hypericum species, a previously undescribed atropisomeric C8-C8' linked dimeric coumarin named bichromonol (1) was isolated from the stem bark of Hypericum roeperianum. The structure was elucidated by MS data and NMR spectroscopy. The absolute configuration at the biaryl axis was determined by comparing the experimental ECD spectrum with those calculated for the respective atropisomers. Bichromonol was tested in cell-based assays for cytotoxicity against MT-4 (CC50 = 54 µM) cells and anti-HIV activity in infected MT-4 cells. It exhibits significant activity at EC50 = 6.6-12.0 µM against HIV-1 wild type and its clinically relevant mutant strains. Especially, against the resistant variants A17 and EFVR, bichromonol is more effective than the commercial drug nevirapine and might thus have potential to serve as a new anti-HIV lead.

3.
IRANIAN JOURNAL OF CHEMISTRY & CHEMICAL ENGINEERING-INTERNATIONAL ENGLISH EDITION ; 40(6):2019-2027, 2021.
Article in English | Web of Science | ID: covidwho-1969992

ABSTRACT

The SARS-CoV-2 has initiated in Wuhan city of China and then extend all around the world as a health emergency. It begins a new research area to produce potential drugs using data-driven approaches to identify potential therapies for the treatment of the virus. This is the time to develop specific antiviral drugs using molecular docking, quantum chemical approaches, and natural products. The protease inhibitors that constitute plant derivatives may become highly efficient to cure virus-prompted illnesses. A systematic study of isolated phytochemicals was executed then frontier molecular orbitals, docking score, molecular descriptors, and active sites were compared with favipiravir, dexamethasone, redeliver, and hydroxychloroquine which are being used against COVID19 nowadays. This is the first study on the phytochemicals of Daphne species to explore their anti-SARS-CoV-2 behavior by molecular docking and quantum chemical methods.

4.
Journal of Animal and Plant Sciences ; 51(3):9313-9342, 2022.
Article in French | CAB Abstracts | ID: covidwho-1865763

ABSTRACT

This study was undertaken to identify herbal remedies that may be involved in the symptomatic management of COVID-19 disease. From a list of 247 medicinal plants, a bibliographic study was carried out with the richness, the floristic composition, the methods of preparation and use and the active principles of the plants as a variable. The importance value of these plants was also calculated. A Principal Component Analysis showed the links between the parts of plants used, the methods of preparation, the symptoms of COVID-19 disease that can be treated and the active ingredients. The results show that 226 medicinal plants divided into 190 genera and 79 families can be used to treat the symptoms of COVID- 19 disease namely otolaryngologic signs, pulmonary signs and general signs. Of these, twenty-eight (28) can relieve the majority of symptoms of COVID-19 disease. These symptoms are rhinorrhea, cough, fever, headache, vomiting, diarrhea, and muscle aches. These plants are mainly prepared in the form of a decoction and administered mainly orally. They mainly contain flavonoids, coumarins, alkaloids, tannins, steroids, terpenoids, saponosides, essential oils, mucilages, quinones, coumarins. The importance value of these plants is between 85.71 and 57.14%. The results also showed that eight (8) groups of medicinal plants can be distinguished according to the organs used, the methods of preparation, the symptoms of the COVID-19 disease treated and the active ingredients. The results of this study could serve as a database for the formulation of improved traditional drugs in the management of symptoms of COVID-19 disease in Cote d'Ivoire.

5.
Journal of Drug Delivery and Therapeutics ; 12(2):87-99, 2022.
Article in English | CAB Abstracts | ID: covidwho-1841785

ABSTRACT

Plant Based Natural Products (PBNPs) have been subject of interest since ancient time due to their use in food, industrial and biomedical applications. Research attention has further augmented to explore their phytochemical composition, properties, and potential application in the post-COVID era. In the present study phytochemical screening has been carried out with Methanolic Leaf Extracts of Moringa oleifera (MLEMO) followed by Gas Chromatography-Mass Spectrometry (GCMS) analysis. Phytochemical analysis of MLEMO revealed the presence of Alkaloids, Carbohydrates, Coumarins, Flavonoids, Glycosides, Phenol, Proteins, Quinones, Saponins, Steroids, Tannins and Terpenoids. Further, GCMS analysis revealed the presence of 41 compounds of which Dihydroxyacetone;Monomethyl malonate;4H-Pyran-4-one,2,3-dihydro- 3,5-dihydroxy-6-methyl;1,3-Propanediol, 2-ethyl-2-(hydroxymethyl);Propanoic acid, 2- methyl-, octyl ester;3-Deoxy-d-mannoic lactone;Sorbitol;Inositol;Cyclohexanemethanol, alpha-methyl-4-(1-methylethyl), Hexadecanoic acid, Methyl palmitate;n-Hexadecanoic acid (Palmitic acid);9-Octadecenoic acid, methyl ester;Phytol;9,12,15-Octadecatrienoic acid;Octadecanoic acid;9-Octadecenamide were prominent. Most of the compounds in the list are bioactive and possess medicinal properties that are expected to serve as a baseline lead for the development of therapeutic agents.

6.
EPMA J ; 12(3): 325-347, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1574890

ABSTRACT

The risks related to the COVID-19 are multi-faceted including but by far not restricted to the following: direct health risks by poorly understood effects of COVID-19 infection, overloaded capacities of healthcare units, restricted and slowed down care of patients with non-communicable disorders such as cancer, neurologic and cardiovascular pathologies, among others; social risks-restricted and broken social contacts, isolation, professional disruption, explosion of aggression in the society, violence in the familial environment; mental risks-loneliness, helplessness, defenceless, depressions; and economic risks-slowed down industrial productivity, broken delivery chains, unemployment, bankrupted SMEs, inflation, decreased capacity of the state to perform socially important programs and to support socio-economically weak subgroups in the population. Directly or indirectly, the above listed risks will get reflected in a healthcare occupation and workload which is a tremendous long-term challenge for the healthcare capacity and robustness. The article does not pretend to provide solutions for all kind of health risks. However, it aims to present the scientific evidence of great clinical utility for primary, secondary, and tertiary care to protect affected individuals in a cost-effective manner. To this end, due to pronounced antimicrobial, antioxidant, anti-inflammatory, and antiviral properties, naturally occurring plant substances are capable to protect affected individuals against COVID-19-associated life-threatening complications such as lung damage. Furthermore, they can be highly effective, if being applied to secondary and tertiary care of noncommunicable diseases under pandemic condition. Thus, the stratification of patients evaluating specific health conditions such as sleep quality, periodontitis, smoking, chronic inflammation and diseases, metabolic disorders and obesity, vascular dysfunction, and cancers would enable effective managemenet of COVID-19-associated complications in primary, secondary, and tertiary care in the context of predictive, preventive, and personalized medicine (3PM).

7.
Pharmaceuticals (Basel) ; 14(11)2021 Nov 05.
Article in English | MEDLINE | ID: covidwho-1534224

ABSTRACT

Diversity-Oriented Synthesis (DOS) represents a strategy to obtain molecule libraries with diverse structural features starting from one common compound in limited steps of synthesis. During the last two decades, DOS has become an unmissable strategy in organic synthesis and is fully integrated in various drug discovery processes. On the other hand, natural products with multiple relevant pharmacological properties have been extensively investigated as scaffolds for ligand-based drug design. In this article, we report the amino dimethoxyacetophenones that can be easily synthesized and scaled up from the commercially available 3,5-dimethoxyaniline as valuable starting blocks for the DOS of natural product analogs. More focus is placed on the synthesis of analogs of flavones, coumarins, azocanes, chalcones, and aurones, which are frequently studied as lead compounds in drug discovery.

8.
Res Pract Thromb Haemost ; 5(7): e12597, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1469557

ABSTRACT

BACKGROUND: Coagulopathy has been reported in severely ill patients with coronavirus disease 2019 (COVID-19). It is unclear whether outpatients with COVID-19 who are treated with vitamin K antagonists (VKAs) have unstable anticoagulation. OBJECTIVE: To assess the stability of VKA therapy in patients with COVID-19 through a case-crossover study. METHODS: Between February and July 2020, we included patients who tested positive for COVID-19 from two anticoagulant clinics in the Netherlands. We collected international normalized ratios (INRs) determined between 26 weeks before infection and 12 weeks after. Time in therapeutic range (TTR) and the variance growth rate (VGR) were calculated within patients. RESULTS: Fifty-one patients with COVID-19 (mean age, 84 years) were included, of whom 15 (29%) were men. Mean TTR in the 26 weeks before COVID-19 was 80% (95% confidence interval [CI], 75-85) compared to 59% (95% CI, 51-68) in the 6 weeks after infection. Mean TTR difference was -23% (95% CI, -32 to -14) with a time above therapeutic range of 38% (95% CI, 30-47) in the 6 weeks after infection. The TTR rose again to 79% (95% CI, 69-89) between 6 and 12 weeks after infection. Also, VGR increased, with a mean increase of 4.8 (95% CI, 2.1-7.5) in the 6 weeks after infection. In the 26 weeks before infection, we registered 19 of 641 (3%) of INR ≥5.0 compared with 35 of 247 (14%) in the 6 weeks after (risk ratio, 4.4; 95% CI, 2.7-7.3). CONCLUSIONS: COVID-19 is associated with a strong decrease in TTR and in therapeutic stability in patients taking VKAs. Additional monitoring in these patients is advised to maximize therapeutic stability.

9.
Front Chem ; 8: 595097, 2020.
Article in English | MEDLINE | ID: covidwho-1094160

ABSTRACT

The pandemic that started in Wuhan (China) in 2019 has caused a large number of deaths, and infected people around the world due to the absence of effective therapy against coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2). Viral maturation requires the activity of the main viral protease (Mpro), so its inhibition stops the progress of the disease. To evaluate possible inhibitors, a computational model of the SARS-CoV-2 enzyme Mpro was constructed in complex with 26 synthetic ligands derived from coumarins and quinolines. Analysis of simulations of molecular dynamics and molecular docking of the models show a high affinity for the enzyme (∆E binding between -5.1 and 7.1 kcal mol-1). The six compounds with the highest affinity show K d between 6.26 × 10-6 and 17.2 × 10-6, with binding affinity between -20 and -25 kcal mol-1, with ligand efficiency less than 0.3 associated with possible inhibitory candidates. In addition to the high affinity of these compounds for SARS-CoV-2 Mpro, low toxicity is expected considering the Lipinski, Veber and Pfizer rules. Therefore, this novel study provides candidate inhibitors that would allow experimental studies which can lead to the development of new treatments for SARS-CoV-2.

10.
Med Chem ; 18(2): 220-237, 2022.
Article in English | MEDLINE | ID: covidwho-1076369

ABSTRACT

BACKGROUND: The Covid-19 virus emerged a few months ago in China, and infections rapidly escalated into a pandemic. OBJECTIVE: To date, there is no selective antiviral agent for the management of pathologies associated with covid-19 and the need for an effective agent against it is essential. METHODS: In this work, two home-made databases from synthetic quinolines and coumarins were virtually docked against viral proteases (3CL and PL), human cell surface proteases (TMPRSS2 and furin) and spike proteins (S1 and S2). Chloroquine, a reference drug without a clear mechanism against coronavirus was also docked on mentioned targets and the binding affinities compared with title compounds. RESULTS: The best compounds of synthetic coumarins and quinolines for each target were determined. All compounds against all targets showed binding affinity between -5.80 to -8.99 kcal/mol in comparison with the FDA-approved drug, Chloroquine, with binding affinity of -5.7 to -7.98 kcal/mol. Two compounds, quinoline-1 and coumarin-24, were found to be effective on three targets - S2, TMPRSS2 and furin - simultaneously, with good predicted affinity between -7.54 to -8.85 kcal/mol. In silico ADME studies also confirmed good oral absorption for them. Furthermore, PASS prediction was calculated and coumarin-24 had higher probable activity (Pa) than probable inactivity (Pi) with acceptable protease inhibitory as well as good antiviral activity against Hepatitis C virus (HCV), Human immunodeficiency virus (HIV) and influenza. CONCLUSION: Quinoline-1 and Coumarin-24 have the potential to be used against Covid-19. Hence these agents could be useful in combating covid-19 infection after further in vitro and in vivo studies.


Subject(s)
Antineoplastic Agents , COVID-19 , Quinolones , Coumarins/pharmacology , Humans , SARS-CoV-2
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