scholarly journals Docking Molecular analysis of potential Drug Paritaprevir against Mycobacterium tuberculosis (Mtb)

2021 ◽  
Author(s):  
IVAN VITO FERRARI ◽  
PAOLO PATRIZIO
Keyword(s):  
Infectious Disease ◽  
Mycobacterium Tuberculosis ◽  
Rna Polymerase ◽  
Binding Affinity ◽  
The Body ◽  
Oral Drug ◽  
Potential Drug ◽  
Autodock Vina ◽  
Ligand Efficiency ◽  
Candidate Drug

Background: Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, which kills 1.8 million annually. This is an infectious disease generally affects the lungs, but can also affect other parts of the body. Mtb RNA polymerase (RNAP) is the target of the first-line antituberculosis drug Rifampin (Rif). We report first time a Potential Drug Paritaprevir against with severe infectious disease , by in Silico approach, using Autodock Vina and Autodock 4 ( or MGL Tool), estimated with Pyrx and AMDock Software, calculating three different important parameters: Binding Affinity ( kcal/mol), estimated Ki ( in nM units) and Ligand Efficiency ( L.E. in kcal/mol). After a selective analysis of over 1000 drugs, processed with Pyrx (a Virtual Screening software for Computational Drug Discovery) in the Ligand Binding site pocket of the protein ( ID PDB 5UHB chain C,DNA-directed RNA polymerase subunit beta), we noticed high values of these 3 parameters mentioned above of Paritaprevir, concluding that it could be an excellent candidate drug for this type of infection. Indeed, from the results of Autodock Vina and Autodock 4 ( or Autodock 4.2 ), implemented with lamarckian genetic algorithm, LGA, trough AMDock Software, This oral drug, approved by FDA in 2014, both by Autodock Vina and Autodock Vina 4 has excellent Binding affinity value, ca. -10.00 kcal/mol, a Ki value 40 nM and Ligand efficiency ca -0.15 kcal/mol. These results are comparable to the drug crystallized in the above-mentioned protein, currently used against TBC.

scholarly journals Literature Review : Pengaruh Batuk Efektif Untuk Pengeluaran Sputum Pada Pasien Tuberculosis

2021 ◽  
Vol 1 ◽  
pp. 1516-1523
Author(s):  
Ida Fauziyah ◽  
Nuniek Nizmah Fajriyah ◽  
Firman Faradisi
Keyword(s):  
Infectious Disease ◽  
Mycobacterium Tuberculosis ◽  
Side Effects ◽  
Literature Review ◽  
The Body ◽  
Forced Expiration ◽  
Shortness Of Breath ◽  
Pharmacological Interventions ◽  
Tuberculosis Patients ◽  
Lung Expansion

AbstractTuberculosis (TB) is in infectious disease that attacks the lungs caused by the bacterium Mycobacterium tuberculosis. Tuberculosis patients usually have symptoms of a prolonged cough, from the cought it can cause shortness of breath in someone who experiences these symtoms because there are too many secretions that are difficult to expel, causing a forced expiration. Forced expiration is one of the non-pharmacological interventions carried out to expel secretions, increase lung expansion, mobilize secretions and prevent side effects of retention of secretions. The purpose of this study was to describe the effect of forced expiration for sputum extraction in tuberculosis patients. Used in this study was a literature review from a database that had been determined used the keywoard tuberculosis, forced expiration, and sputum extraction. Obtained after forced expiration was reduced in the number of secretions in the patient. This study is that forced expiration can effectively reduce the amount of secretions in the body of tuberculosis patients. Keywoard: Forced expiration; Sputum extraction; Tuberculosis (Pulponary tuberculosis) AbstrakTuberculosis (TB) adalah salah satu penyakit infeksi yang menyerang bagian paru-paru disebabkan oleh bakteri mycrobacterium tuberculosis. Pendertia tuberculosis biasanya memiliki gejala batuk yang berkepanjangan, dari batuk tersebut dapat menyebabkan sesak nafas pada seseorang yang mengalami gejala tersebut karena terlalu banyak sekret yang susah untuk dikeluarkan sehingga menyebabkan batuk efektif. Batuk efektif adalah salah satu tindakan non farmakologi yang dilakukan untuk pengeluaran sekresi, meningkatkan ekspansi paru, memobilisasi sekret dan mencegah efek samping dari retensi sekresi. Dari karya tulis ilmiah adalah untuk mengetahui gambaran tentang pengaruh batuk efektif untuk pengeluaran sputum pada pasien tuberculosis. Metode yang dilakukan dalam penelitian adalah literature review dari database yang telah ditentukan dengan menggunakan kata kunci Tuberculosis, latihan batuk efektif, dan pengeluaran sputum. Hasil yang didapatkan setelah dilakukan tindakan latihan batuk efektif yaitu banyaknya sekret pada pasien mulai berkurang. Kesimpulan karya tulis ilmiah ini bahwa tindakan latihan batuk efektif dapat mengurangi jumlah sekresi yang ada pada tubuh pasien tuberculosis.Kata kunci: Latihan batuk efektik; Pengeluaran Sputum; Tuberculosis ( TB Paru)

scholarly journals Development of Novel Oral Formulations of Disulfide Antioxidants Based on Porous Silica for Controlled Release of the Drugs

Materials ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 963
Author(s):  
Ekaterina S. Dolinina ◽  
Elena V. Parfenyuk
Keyword(s):  
Antioxidant Activity ◽  
Surface Chemistry ◽  
Sol Gel ◽  
Porous Silica ◽  
The Body ◽  
Oral Drug ◽  
Therapeutic Concentration ◽  
Release Process ◽  
Zero Order Kinetics ◽  
Long Time

Powerful antioxidant α-lipoic acid (LA) exhibits limited therapeutic efficiency due to its pharmacokinetic properties. Therefore, the purpose of this work was to evaluate the ability of silica-based composites of LA as well as its amide (lipoamide, LM), as new oral drug formulations, to control their release and maintain their therapeutic concentration and antioxidant activity in the body over a long time. The composites synthesized at different sol–gel synthesis pH and based on silica matrixes with various surface chemistry were investigated. The release behavior of the composites in media mimicking pH of digestive fluids (pH 1.6, 6.8, and 7.4) was revealed. The effects of chemical structure of the antioxidants, synthesis pH, surface chemistry of the silica matrixes in the composites as well as the pH of release medium on kinetic parameters of the drug release and mechanisms of the process were discussed. The comparative analysis of the obtained data allowed the determination of the most promising composites. Using these composites, modeling of the release process of the antioxidants in accordance with transit conditions of the drugs in stomach, proximal, and distal parts of small intestine and colon was carried out. The composites exhibited the release close to the zero order kinetics and maintained the therapeutic concentration of the drugs and antioxidant effect in all parts of the intestine for up to 24 h. The obtained results showed that encapsulation of LA and LM in the silica matrixes is a promising way to improve their bioavailability and antioxidant activity.

scholarly journals Bioactive Antidiabetic Flavonoids from the Stem Bark of Cordia dichotoma Forst.: Identification, Docking and ADMET Studies

Molbank ◽  
10.3390/m1234 ◽  
2021 ◽  
Vol 2021 (2) ◽  
pp. M1234
Author(s):  
Nazim Hussain ◽  
Bibhuti Bhushan Kakoti ◽  
Mithun Rudrapal ◽  
Khomendra Kumar Sarwa ◽  
Ismail Celik ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Mass Spectroscopy ◽  
Column Chromatography ◽  
Stem Bark ◽  
Antidiabetic Activity ◽  
Bark Extract ◽  
Computational Studies ◽  
Autodock Vina ◽  
Online Tool

Cordia dichotoma Forst. (F. Boraginaceae) has been traditionally used for the management of a variety of human ailments. In our earlier work, the antidiabetic activity of methanolic bark extract of C. dichotoma (MECD) has been reported. In this paper, two flavonoid molecules were isolated (by column chromatography) and identified (by IR, NMR and mass spectroscopy/spectrometry) from the MECD with an aim to investigate their antidiabetic effectiveness. Molecular docking and ADMET studies were carried out using AutoDock Vina software and Swiss ADME online tool, respectively. The isolated flavonoids were identified as 3,5,7,3′,4′-tetrahydroxy-4-methoxyflavone-3-O-L-rhamnopyranoside and 5,7,3′-trihydroxy-4-methoxyflavone-7-O-L-rhamnopyranoside (quercitrin). Docking and ADMET studies revealed the promising binding affinity of flavonoid molecules for human lysosomal α-glucosidase and human pancreatic α-amylase with acceptable ADMET properties. Based on computational studies, our study reports the antidiabetic potential of the isolated flavonoids with predictive pharmacokinetics profile.

scholarly journals Tuberculosis in Otorhinolaryngology: Clinical Presentation and Diagnostic Challenges

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Rajiv C. Michael ◽  
Joy S. Michael
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Pulmonary Tuberculosis ◽  
Clinical Presentation ◽  
Extrapulmonary Tuberculosis ◽  
Common Type ◽  
The Body ◽  
Diagnostic Challenge ◽  
Cervical Adenitis ◽  
Important Form

Tuberculosis affects all tissues of the body, although some more commonly than the others. Pulmonary tuberculosis is the most common type of tuberculosis accounting for approximately 80% of the tuberculosis cases. Tuberculosis of the otorhinolaryngeal region is one of the rarer forms of extrapulmonary tuberculosis but still poses a significant clinical and diagnostic challenge. Over three years, only five out of 121 patients suspected to have tuberculosis of the otorhinolaryngeal region (cervical adenitis excluded) hadMycobacterium tuberculosisculture-proven disease. Additional 7 had histology-proven tuberculosis. Only one patient had concomitant sputum-positive pulmonary tuberculosis. We look at the various clinical and laboratory aspects of tuberculosis of the otorhinolaryngeal region that would help to diagnose this uncommon but important form of extrapulmonary tuberculosis.

scholarly journals Molecular Docking Senyawa Gingerol dan Zingiberol pada Tanaman Jahe sebagai Penanganan COVID-19

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Belinda D. P. M. Ratu ◽  
Widdhi Bodhi ◽  
Fona Budiarso ◽  
Billy J. Kepel ◽  
. Fatimawali ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Amino Acid Residues ◽  
Autodock Vina ◽  
Discovery Studio ◽  
Main Protease ◽  
Docking Method ◽  
Pubmed Database ◽  
Almost All ◽  
The Impact

Abstract: COVID-19 is a new disease. Many people feel the impact of this disease. There is no definite cure for COVID-19, so many people use traditional medicine to ward off COVID-19, including ginger. This study aims to determine whether there is an interaction between compounds in ginger (gingerol and zingiberol) and the COVID-19’s main protease (6LU7). This study uses a molecular docking method using 4 main applications, namely Autodock Tools, Autodock Vina, Biovia Discovery Studio 2020, and Open Babel GUI. The samples used were gingerol and zingiberol compounds in ginger plants downloaded from Pubchem. The data used in this study used Mendeley, Clinical Key, and PubMed database. The study showed that almost all of the amino acid residues in the gingerol compound acted on the 6LU7 active site, whereas the zingiberol did not. The results of the binding affinity of ginger compounds, both gingerol and zingiberol, do not exceed the binding affinity of remdesivir, a drug that is widely researched as a COVID-19 handling drug. In conclusion, gingerol and zingiberol compounds in ginger can’t be considered as COVID-19’s treatment.Keywords: molecular docking, gingerol, zingiberol Abstrak: COVID-19 merupakan sebuah penyakit yang baru. Banyak masyarakat yang merasakan dampak dari penyakit ini. Belum ada pengobatan pasti untuk menyembuhkan COVID-19, sehingga banyak masyarakat yang menggunakan pengobatan tradisional untuk menangkal COVID-19, termasuk jahe. Penelitian ini bertujuan untuk mengetahui apakah ada interaksi antara senyawa pada jahe (gingerol dan zingiberol) dengan main protease COVID-19 (6LU7). Penelitian ini menggunakan metode molecular docking dengan menggunakan 4 aplikasi utama, yaitu Autodock Tools, Autodock Vina, Biovia Discovery Studio 2020, dan Open Babel GUI. Sampel yang digunakan yaitu senyawa gingerol dan zingiberol pada tanaman jahe yang diunduh di Pubchem. Data yang digunakan dalam penelitian ini menggunakan database Mendeley, Clinical Key, dan PubMed. Penelitian menunjukkan bahwa hampir semua residu asam amino pada senyawa gingerol bekerja pada sisi aktif 6LU7, sedangkan tidak demikian pada zingiberol. Hasil binding affinity senyawa jahe, baik gingerol maupun zingiberol tidak  melebihi binding affinity remdesivir, obat yang banyak diteliti sebagai obat penanganan COVID-19. Sebagai simpulan, senyawa gingerol dan zingiberol pada tanaman jahe tidak dapat dipertimbangkan sebagai penanganan COVID-19Kata Kunci: molecular docking, gingerol, zingiberol

scholarly journals Design and Synthesis of Antiviral Iminoribitol C-Nucleosides

2021 ◽  
Author(s):  
◽  
Ye Li
Keyword(s):  
Antiviral Activity ◽  
Rna Polymerase ◽  
Nucleoside Analogue ◽  
Rna Viruses ◽  
Active Form ◽  
Building Blocks ◽  
The Body ◽  
Nucleoside Analogues ◽  
Federal Drug Administration ◽  
Pharmacologically Active

<p>Infections caused by RNA viruses, such as Ebola and Zika, continue to exist worldwide as significant public health problems. In response to the urgent need for safer and more efficacious treatment options to treat infections caused by RNA viruses, the pharmaceutical and biotechnology industries have devoted significant efforts over the last two decades to discovering and developing new antiviral agents. One such antiviral, Sofosbuvir®, was approved by the US Federal Drug Administration (FDA) in 2014 and has revolutionized the treatment of Hepatitis-C. Sofosbuvir® was the second largest selling drug in the world in 2016 and in just twenty-one months Gilead reported sales worth $26.6 billion USD.The strategy of using nucleoside analogues to inhibit viral RNA dependent RNA polymerase(RdRp)has been pursued since the 1970s, and exemplified bythe discovery and development of ribavirin. The natural substrates of RNA polymerases are nucleoside triphosphates and often the efficacy of nucleoside analogues as antivirals are dependent on their ability to be converted by the host or virus to mono-, di-, and ultimately tri-phosphate analogues which block the active site of RNA polymerase as an analogue of the substrate causing chain termination. Recently Biocryst Pharmaceuticals (Biocryst) described the anti-viral properties of Immucillin-A (Galidesivir), an iminoribitol based nucleoside analogue, which was found to have broad spectrum antiviral activity especially against RNA viruses including Ebola. Researchers at the Ferrier Research Institute (Ferrier) have synthesizedan analogue of Immucillin-A, 8-aza-Immucillin-A (AIA) which shows comparable activityto Immucillin-A, in anti-viral screens against Ebola, and this antiviral activity forms part of a US patent application. The Ferrier is keen to further exemplify this compound class through the synthesis of analogues of both Immucillin-A and AIA as well as improve the overall synthesis of the lead compound AIA.Included as part of this study is the synthesis of pro-drugs of these iminoribitol based nucleoside analogues. Prodrugs are metabolized inside the body and are often converted to the corresponding pharmacologically active form. In general, prodrug strategies have improved the bioavailability and efficacy of many drugs. In particular, prodrugs strategies involving nucleoside analogue antivirals, which target RNA polymerase, have been particularly effective as they ensure conversion to the monophosphate in vivo. Conversion to the 5’-monophosphate form of a nucleoside analogue is the rate limiting step to the inhibition of the RNA polymerase –prior to its conversion to the triphosphateanalogue. The prodrug is effectively a protected monophosphate, and is then readily converted to monophosphate by the host and then onto the di-and tri-phosphate by kinases in both the host and virus. ProTide prodrugs, such as Sofosbuvir® provide a verified strategy for improving anti-viral activity and hence our desire to synthesize pro-drugs of all our iminoribitol based nucleoside analogues. This research thesis also involved repeating the known synthesis of the Immucillins, in particular, Immucillin-H (Forodesine), which requires in excess of 20 linear synthetic steps to make. The linear synthetic route to Immucillin-H was used instead of the more convenient convergent method developed by the Ferrier as several key synthetic intermediates in this progress were utilized in the attempted synthesis of some of the planned nucleoside analogues of AIA. As part of this work the candidate learned aspects of scaling up chemical reactions andthe critical analysis of both reaction hazards and reagent compatibilities at scale. Where possible and given the number of synthetic steps involved the candidate was also interested in improving the yields of the building blocks involved in the synthesis of the Immucillins with limited success.</p>

scholarly journals Molecular Docking Analysis of the T450A Mutation of the Gene rpoB Mycobacterium leprae from Leprosy Patients in Papua, West Papua and North Maluku, Indonesia

2021 ◽  
pp. 3578-3584
Author(s):  
Yustinus Maladan ◽  
Hana Krismawati ◽  
Tri Wahyuni ◽  
Hotma Martogi Lorensi Hutapea ◽  
Muhammad Fajri Rokhmad ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Binding Affinity ◽  
Rpob Gene ◽  
Ramachandran Plot ◽  
Docking Analysis ◽  
West Papua ◽  
Leprosy Patients ◽  
Subunit B ◽  
Molecular Docking Analysis

Leprosy persists to be a health problem in Indonesia, especially in the provinces of North Maluku, West Papua and Papua. Early diagnosis and complete treatment with multidrug therapy (MDT) remain the key strategy for reducing the disease burden. One of the major components of MDT is rifampicin which in certain cases in several countries, M. leprae resistance to this drug issue has been reported albeit only a few. This research aimed to detect and analyze polymorphism in M. leprae rpoB gene that was isolated from leprosy patients in three provinces: North Maluku Province, West Papua Province and Papua Province, Indonesia. The identification of mutations in the M. leprae rpoB gene was carried out by aligning the results of DNA sequencing with the reference strain. The 3D structure of rpoB was derived using the Swiss Model. The T450A, S456L, and H451Y variants of RNA Polymerase B subunits were constructed using FoldX based on the wild-type structure. The structures were repaired, and protein stability was evaluated using foldX under the Yasara viewer. The QC of the rpoB M. leprae homology models was conducted with Ramachandran Plot modeling using PROCHECK. The difference in binding affinity between native protein and T450A, S456L, and H45I variants were analyzed using molecular docking. rpoB gene of M. leprae contains a mutation found in nucleotide of 1348 bp. The mutation triggered the conversion of the amino acid Threonine to Alanine in the amino acid to 450 rpoB subunit B. The structure of 3D RNA Polymerase Subunit B was constructed using rpoB Mycobacterium tuberculosis with PDB code 5UH5 as template. According to Ramachandran Plot, the percentage of residues in the most favored regions are 91.9%, and there was no significant number of residues in the disallowed regions. The results of molecular docking showed that the T450A variant had the same binding affinity with the native protein which was -8.9 kcal. Binding affinity on the S456L and H451Y variants increased by -7.3 kcal and -8.2 kcal, respectively. According to Molecular Docking analysis, T450A variant did not affect the energy binding between RNA polymerase and rifampicin.

scholarly journals The thick waxy coat of mycobacteria, a protective layer against antibiotics and the host's immune system

2020 ◽  
Vol 477 (10) ◽  
pp. 1983-2006 ◽  
Author(s):  
Sarah M. Batt ◽  
David E. Minnikin ◽  
Gurdyal S. Besra
Keyword(s):  
Infectious Disease ◽  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Immune System ◽  
Mortality Rate ◽  
Cell Envelope ◽  
Protective Layer ◽  
Structure And Function ◽  
Complex Lipids ◽  
And Function

Tuberculosis, caused by the pathogenic bacterium Mycobacterium tuberculosis (Mtb), is the leading cause of death from an infectious disease, with a mortality rate of over a million people per year. This pathogen's remarkable resilience and infectivity is largely due to its unique waxy cell envelope, 40% of which comprises complex lipids. Therefore, an understanding of the structure and function of the cell wall lipids is of huge indirect clinical significance. This review provides a synopsis of the cell envelope and the major lipids contained within, including structure, biosynthesis and roles in pathogenesis.

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