Abstract:
:The World Health Organization has classified the COVID-19 outbreak a pandemic which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and declared it a global health emergency. Repurposing drugs with minimum side effects are one approach to quickly respond in attempt to prevent the spread of COVID-19. SARS-CoV-2 encodes several RNA processing enzymes that are unusual and unique for single-stranded RNA viruses, including Nsp15, a hexameric endoribonuclease that discriminatory cleaves immediately 3' of uridines. The structure of SARS-CoV-2 Nsp15 is reported to be homologous to that of the Nsp15 endoribonucleases of SARS-CoV and MERS-CoV, but it exhibits differences that may contribute to the greater virulence of SARS-CoV-2. This study aimed to identify drugs that targeted SARS-COV-2 Nsp15 using a molecular docking-based virtual screening of a library containing 10,000 approved and experimental drugs. The molecular docking results revealed 19 medications that demonstrated a good ability to inhibit Nsp15. Among all the candidated 19 drugs only five FDA approved drugs were used for further investigation by molecular dynamics simulation, the stability of Nsp15-ligand system was evaluated by calculating the RMSD, RMSF, radius of gyration and hydrogen bond profile. Furthermore, MM-PBSA method was employed to validate the binding affinity. According to the obtained results of MD, the complex of Olaparib was showed more stability and lower binding free energy than the control inhibitor during MD simulation time. Finally, we suggest that Olaparib is a potential drug for treating patients infected with SARS-CoV-2 and provide insight into the host immune response to viral RNA. Communicated by Ramaswamy H. Sarma.
journal_name
J Biomol Struct Dynjournal_title
Journal of biomolecular structure & dynamicsauthors
Al-Rashedi NAM,Munahi MG,Ah ALObaidi Ldoi
10.1080/07391102.2020.1863265subject
Has Abstractpub_date
2020-12-27 00:00:00pages
1-14eissn
0739-1102issn
1538-0254pub_type
杂志文章abstract::Adenosine receptors (ARs) belong to family A of GPCRs that are involved in many diseases, including cerebral and cardiac ischemic diseases, immune and inflammatory disorders, etc. Thus, they represent important therapeutic targets to treat these conditions. Computational techniques such as molecular dynamics (MD) simu...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2018.1564700
更新日期:2019-11-01 00:00:00
abstract::Abstract Using high frequency antiphase NMR spectroscopy and computer simulations of the antiphase spectra, we studied the equlibria in the sugar conformations in the DNA duplex 11-mer containing the AAA tract surrounded by cytosines. We demonstrate that at the 3'-end of the A-tract, the sugar switches from the comm...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2000.10506637
更新日期:2000-01-01 00:00:00
abstract::Enzymes involved in the pyrimidine biosynthesis pathway have become an important target for the pharmacological intervention. One among those enzymes, Aspartate Trans Carbamoylase (ATCase), catalyses the condensation of aspartate and carbamoyl phosphate to form N-carbamoyl-l-aspartate and inorganic phosphate. The pres...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2013.782825
更新日期:2014-04-01 00:00:00
abstract::The InhA inhibitors play key role in mycolic acid synthesis by preventing the fatty acid biosynthesis pathway. In this present article, Pharmacophore modelling and molecular docking study followed by in silico virtual screening could be considered as effective strategy to identify newer enoyl-ACP reductase inhibitors....
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2018.1465852
更新日期:2019-04-01 00:00:00
abstract::The structure of the nonclassical pi kappa base pair (7-methyl-oxoformycin B. . .2,4-diaminopyrimidine) was studied at the ab initio Hartree-Fock (HF) and MP2 levels using the 6-31G* and 6-31G** basis sets. The pi kappa base pair is bound by three parallel hydrogen bonds with the donor-acceptor-donor recognition patte...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1995.10508797
更新日期:1995-04-01 00:00:00
abstract::Traditional approaches for macromolecular structure elucidation, including NMR, crystallography and cryo-EM have made significant progress in defining the structures of protein-protein complexes. A substantial number of macromolecular structures, however, have not been examined with atomic detail due to sample size an...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2001.10506750
更新日期:2001-12-01 00:00:00
abstract::The availability of a significant number of the structures of helical membrane proteins has prompted us to investigate the mode of helix-helix packing. In the present study, we have considered a dataset of alpha-helical membrane proteins representing structures solved from all the known superfamilies. We have describe...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2009.10507284
更新日期:2009-06-01 00:00:00
abstract::Analogues of purine bases are highly relevant in the biological context and have been implicated as drug molecules for therapy against a number of diseases. Additionally, these molecules have been implicated to have a role in the prebiotic RNA world. However, experimental data on the structures of these molecules in a...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2012.745821
更新日期:2014-01-01 00:00:00
abstract::The conformational space available to GnRH and lGnRH-III was compared using 5.2 ns constant temperature and pressure molecular dynamics simulations with explicit TIP3P solvation and the AMBER v. 5.0 force field. Cluster analysis of both trajectories resulted in two groups of conformations. Results of free energy calcu...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2001.10506703
更新日期:2001-04-01 00:00:00
abstract::The interaction of calf-thymus DNA with cobalt-hexammine and cobalt-pentammine cations was investigated, in aqueous solution at pH 6-7 with cation/DNA(phosphate) molar ratios r = 1/80, 1/40, 1/20, 1/10, 1/4, 1/2 and 1, using Fourier Transform infrared (FTIR) difference spectroscopy. Correlations between spectral chang...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1993.10508711
更新日期:1993-08-01 00:00:00
abstract::Acinetobacter baumannii, a Gram-negative pathogen causes nosocomial infections including pneumonia, urinary tract and respiratory infections. Carbapenem group of β-lactam antibiotics are routinely used to treat A. baumannii including multidrug-resistant clinical strains. The emergence of New Delhi Metallo-β-lactamase ...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2012.706075
更新日期:2013-01-01 00:00:00
abstract::The sharp spurt in positive cases of novel coronavirus-19 (SARS-CoV-2) worldwide has created a big threat to human. In view to expedite new drug leads for COVID-19, Main Proteases (Mpro) of novel Coronavirus (SARS-CoV-2) has emerged as a crucial target for this virus. Nitric oxide (NO) inhibits the replication cycle o...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1790038
更新日期:2020-07-08 00:00:00
abstract::Two aminobenzoic acid derivatives DAB-0 and DAB-1 showed distinct biological properties on murine bladder cancer (BCa) cell line MB49-I. In contrast to DAB-1, DAB-0 does not possess any anti-inflammatory activity and is less toxic. Furthermore, DAB-0 does not interfere with INFγ-induced STAT1 activation and TNFα-induc...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1719889
更新日期:2021-01-01 00:00:00
abstract::Plasma membrane of each micro-organism has a unique set of lipid composition as a consequence of the environmental adaptation or a response to exposure to antimicrobial peptides (AMPs) as antibiotic agents. Understanding the relationship between lipid composition and action of antimicrobial peptides or considering how...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2012.737295
更新日期:2013-12-01 00:00:00
abstract::The effect of ligand interacting with native DNA by two types on the parameters of helix-coil transition in homopolymers is considered using the most probable distribution method (Yu.S. Lazurkin et al., Biopolymers 1970). It is shown that at a small relative concentration of ligand the melting enthalpy (delta H) of DN...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1990.10507793
更新日期:1990-08-01 00:00:00
abstract::Previous research has described the interaction between the novel molecule diethidium (2,7-diamino 9-[2,7 diamino 10-N-phenanthridium] 10-N-phenanthridium) (Figure 1) and B-form DNA. Our goal is the elucidation of diethidium as the first member of a novel class of drugs which are potential pharmaceutical agents. This ...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1997.10508946
更新日期:1997-08-01 00:00:00
abstract::Beta-N-acetyl-D-glucosaminidase (NAGase, EC.3.2.1.52), which catalyzes the cleavage of N-acetylglucosamine polymers, is a composition of chitinase and cooperates with endo-chitinase and exo-chitinase to disintegrate chitin into N-acetylglucosamine (NAG). In this investigation, A NAGase from green crab (Scylla serrata)...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2009.10507266
更新日期:2009-02-01 00:00:00
abstract::The fragile X triplet repeats, (GCC)n x (GGC)n are located at the 5' untranslated region of the FMR-1 gene. Inordinate repeat expansion and hyper-methylation of the CpG islands inside the repeat lead to the suppression of the FMR-1 gene and the subsequent onset and progression of the disease. Previously, we have shown...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1998.10508989
更新日期:1998-02-01 00:00:00
abstract::The inhibitory efficacy of two substituted coumarin derivatives on the activity of neurodegenerative enzyme acetylcholinesterase (AChE) was assessed in aqueous buffer as well as in the presence of human serum albumin (HSA) and compared against standard cholinergic AD drug, Donepezil (DON). The experimental data reveal...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2018.1465853
更新日期:2019-04-01 00:00:00
abstract::Thermodynamic parameters of coaxial stacking at complementary helix-helix interfaces GX*pYG/CZVC (X,Y=A,C,T,G;*-nick) created by contiguous oligonucleotide hybridization were determined. The data obtained were compared to the thermodynamic parameters of coaxial stacking at the interfaces CX*pYC/GZVG. Multiple linear r...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2003.10506940
更新日期:2003-12-01 00:00:00
abstract::Partial proteolysis of the lambda cI repressor has been carried out systematically with trypsin, chymotrypsin, elastase, endoproteinase Glu-C, kallikrein, and thrombin. The cleavage sites have been determined by (i) comparison of fragments produced and observed in SDS-polyacrylamide gel with known fragments and plots ...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2008.10507249
更新日期:2008-12-01 00:00:00
abstract::Haloxyfop was reported to exhibit inhibition effect targeting Mycobacterium tuberculosis and pathogenic parasites. To pave its way for drug development, more research is required to determine the affinities interacting with biological receptors in vivo. In this work, the interactions of Haloxyfop with two model transp...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2018.1552624
更新日期:2019-10-01 00:00:00
abstract::It is well established that GAA/TTC base triplet expansion is the cause of degenerative disorder in Freidreich's Ataxia. It is also known that these repeat sequences fold back to form the unusual intramolecular triple helix structures in DNA of the type Pyrimidine *Purine *Pyrimidine or Purine *Purine*Pyrimidine. In t...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2002.10506775
更新日期:2002-02-01 00:00:00
abstract::Non-obstructive azoospermia (NOA) is the most clinical problem in case of infertility. About 70% of NOA patients are idiopathic with uncharacterized molecular mechanisms. This study aimed to analyze the possible pathogenic miRNA-target gene interaction and lncRNA-miRNA association involved in NOA. In the current study...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2021.1875879
更新日期:2021-01-26 00:00:00
abstract::Notch is a single-pass transmembrane receptor protein which is composed of a short extracellular region, a single-pass transmembrane domain and a small intracellular region. Notch ligand like Delta, member of the DSL protein family, is also single-pass transmembrane protein. It has been demonstrated that of the 36 EGF...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章,收录出版
doi:10.1080/07391102.2011.10507386
更新日期:2011-10-01 00:00:00
abstract::The reproducibility of melting curves for repeated hybridizations of target DNA with generic oligonucleotide microchips is shown experimentally to depend on the character of matching between fragments of target DNA and immobilized oligonucleotides. The reproducibility of melting curves is higher for the perfect match ...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2001.10506709
更新日期:2001-06-01 00:00:00
abstract::Phospholipase A(2) belongs to a super family of enzymes that is massively over expressed in a variety of severe inflammatory diseases, which degrades membrane phospholipids. It has also been reported that this activity leads to loss of tissue, organ integrity and function. This enzyme is an important target for anti-i...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2010.10507333
更新日期:2010-02-01 00:00:00
abstract::Transient interactions between cancer stem cells and components of the tumor microenvironment initiate various signaling pathways crucial for carcinogenesis. Predominant hyaluronan (HA) receptor, CD44 is structurally and functionally one of the most variable cell surface receptors having the potential to generate a di...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2016.1142476
更新日期:2017-02-01 00:00:00
abstract::A molecular dynamics simulation of the Sm binding site from human U4 snRNA was undertaken to determine the conformational flexibility of this region and to identify RNA conformations that were important for binding of the Sm proteins. The RNA was fully-solvated (>9,000 water molecules) and charge neutralized by inclus...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2000.10506670
更新日期:2000-12-01 00:00:00
abstract::Ornithine decarboxylase (ODC) is an enzyme that initiates polyamine synthesis in human. Polyamines play key roles in cell-cell adhesion, cell motility and cell cycle regulation. Higher synthesis of polyamines also occurs in rapidly proliferating cancer cells are mediated by ODC. As per earlier studies, di-flouro-methy...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2018.1439772
更新日期:2019-02-01 00:00:00