Efficacy of neuraminidase (NA) inhibitors against H1N1 strains of different geographical regions: an in silico approach

Khan, Asad U.; Shakil, Shazi; Lal, Sunil K.

doi:10.1007/s12088-009-0065-2

Cited by 5 publications

(3 citation statements)

References 16 publications

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“…This was strongly supported by the experimental studies that suggested a better activity of doripenem over other carbapenems against carbapenemase producing bacteria [19]. Moreover, in a similar 2009 study authors have used interaction energies of docking to compare the efficacy of different neuraminidase inhibitors against newly evolved strains of H1N1 viruses [20]. It is important to mention here that more experimental studies are needed to establish a precise relationship between MIC and interaction energy.…”

Section: Discussionmentioning

confidence: 80%

Interaction of CTX-M-15 enzyme with cefotaxime: a molecular modelling and docking study

Shakil¹,

Khan²

2010

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Extendedspectrum βlactamases (ESBLs) are the bacterial enzymes that make them resistant to advanced-generation cephalosporins. CTXM enzymes (the most prevalent ESBLtype) target cefotaxime. Aims of the study were: Modelling of CTXM enzyme from blaCTXM sequences of clinical Escherichia coli isolatesDocking of cefotaxime with modelled CTXM enzymes to identify amino acid residues crucial to their interaction To hypothesize a possible relationship between ’interaction energy of the docked enzymeantibiotic complex‘ and ’minimum inhibitory concentration (MIC) of the antibiotic against the bacteria producing that enzyme‘. Seven E. coli strains of clinical origin which were confirmed as PCRpositive for blaCTXM were selected for the study. C600 cells harboring cloned blaCTXM were tested for ESBLproduction by doubledisksynergy test. BLAST analysis confirmed all the blaCTX-M genes as blaCTXM15. Four of the 7 strains were found to be clonally related. Modelling was performed using Swiss Model Server. Discovery Studio 2.0 (Accelrys) was used to prepare Ramachandran plots for the modelled structures. Ramachandran Zscores for modelled CTXM enzymes from E. coli strains D8, D183, D253, D281, D282, D295 and D296 were found to be 0.449, 0.096, 0.027, 0.043, 0.032, 1.249 and 1.107, respectively. Docking was performed using Hex 5.1 and the results were further confirmed by Autodock 4.0. The amino acid residues Asn 104, Asn132, Gly 227, Thr 235, Gly 236, and Ser237 were found to be responsible for positioning cefotaxime into the active site of the CTXM15 enzyme. It was found that cefotaxime MICs for the CTXM15producers increased with the increasing negative interaction energy of the enzymeantibiotic complex.

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Section: Discussionmentioning

confidence: 80%

Interaction of CTX-M-15 enzyme with cefotaxime: a molecular modelling and docking study

Shakil¹,

Khan²

2010

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“…In earlier studies it has also been observed that the calculated binding free energy values are with inverse proportional to the corresponding MIC values for enzyme-drug complexes [ 15 ]. Moreover, previously, authors have used interaction energies of docking to compare the efficacy of different neuraminidase inhibitors against newly evolved strains of H1N1 viruses [ 16 ]. Our data is consistent with the earlier studies [ 17 , 18 ].…”

Section: Resultsmentioning

confidence: 99%

Molecular docking analysis of new generation cephalosporins interactions with recently known SHV-variants

Khan¹,

Baig²,

Wadhwa³

2011

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Extended-spectrum-β-lactamases (ESBLs), constitutes the growing class of betalactamses, these are enzymes produced by bacteria which impart resistance against advanced-generation-cephalosporins. SHV enzymes are among the most prevalent ESBLs. The mode of molecular interactions of recent SHV-variants to advanced generation cephalosporins has not been reported yet. This is the first time we are reporting the insilico study of these recent variants with new generation cephaosporins. Homology models for SHV-105, SHV-95, SHV-89, SHV-61 and SHV-48 were generated using MODELLER9v3. New generation Cephalosporins were selected to target the active site amino acid residues of these modeled SHV enzymes for predicting comparative efficacies of these inhibitors against the said enzymes on the basis of interaction energies of docking. The docked complexes were analyzed by using DISCOVERY STUDIO 2.5. In this study A237, S70, K234, R275, N132, R244 and S130 were found crucial to the correct positioning of drugs within the binding site of SHV enzymes in 11, 6, 6, 6, 5, 5 and 5 instances, respectively. On the basis of interaction energy and Ki calculations cefatoxime emerged as the most efficient among the other advanced cephalosporins against all the studied SHV variants, excluding SHV-48 where ceftazidime was found to be most effective drug. Furthermore, this study identified amino acid residues crucial to ‘SHV-Cephalosporins’ interactions and this information will be useful in designing effective and versatile drug candidates.

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“…Although oseltamivir and zanamivir are the best drugs for the prophylaxis and treatment of inuenza infections, the emergence of drug-resistant variants is a major problem in antiviral therapy. 9 The NA-R292K mutation has been isolated from (A/Shanghai/1/2013) H7N9 inuenza virus. Viruses with this mutation cause reduced sensitivity to oseltamivir and zanamivir.…”

Section: Introductionmentioning

confidence: 99%

Jatrorrhizine hydrochloride potentiates the neuraminidase inhibitory effect of oseltamivir towards H7N9 influenza

et al. 2015

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Efficacy of neuraminidase (NA) inhibitors against H1N1 strains of different geographical regions: an in silico approach

Cited by 5 publications

References 16 publications

Interaction of CTX-M-15 enzyme with cefotaxime: a molecular modelling and docking study

Interaction of CTX-M-15 enzyme with cefotaxime: a molecular modelling and docking study

Molecular docking analysis of new generation cephalosporins interactions with recently known SHV-variants

Jatrorrhizine hydrochloride potentiates the neuraminidase inhibitory effect of oseltamivir towards H7N9 influenza

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