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Sudha Ramaiah

Bio: Sudha Ramaiah is an academic researcher from VIT University. The author has contributed to research in topics: Medicine & Gene. The author has an hindex of 18, co-authored 85 publications receiving 1166 citations.

Papers published on a yearly basis

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Journal ArticleDOI
TL;DR: The flavonoid quercetin with highest binding energy against NS2B-NS3 protease which is evident by the formation of six hydrogen bonds with the amino acid residues at the binding site of the receptor is found.
Abstract: Dengue virus belongs to the virus family Flaviviridae. Dengue hemorrhagic disease caused by dengue virus is a public health problem worldwide. The viral non structural 2B and 3 (NS2B-NS3) protease complex is crucial for virus replication and hence, it is considered to be a good anti-viral target. Leaf extracts from Carica papaya is generally prescribed for patients with dengue fever, but there are no scientific evidences for its anti-dengue activity; hence we intended to investigate the anti-viral activity of compounds present in the leaves of Carica papaya against dengue 2 virus (DENV-2). We analysed the anti-dengue activities of the extracts from Carica papaya by using bioinformatics tools. Interestingly, we find the flavonoid quercetin with highest binding energy against NS2B-NS3 protease which is evident by the formation of six hydrogen bonds with the amino acid residues at the binding site of the receptor. Our results suggest that the flavonoids from Carica papaya have significant anti-dengue activities. Abbreviations ADME - Absorption, distribution, metabolism and excretion, BBB - Blood brain barrier, CYP - Cytochrome P450, DENV - – Dengue virus, DHF - Dengue hemorrhagic fever, DSS - Dengue shock syndrome, GCMS - – Gas chromatography- Mass spectrometry, MOLCAD - Molecular Computer Aided Design, NS - Non structural, PDB - Protein data bank, PMF - Potential Mean Force.

114 citations

Journal ArticleDOI
05 Feb 2018-Gene
TL;DR: The distinctive attribute mentioned in this review is not only to provide an overview of tools and web servers for gene and protein-protein interaction (PPI) network analysis but also to extract useful and meaningful information from the interaction networks.

110 citations

Journal ArticleDOI
TL;DR: The T118M mutation in PMP22 gene is associated with Charcot Marie Tooth, type 1A and resulted in the overall increase in the stability of the mutant protein, which shows marked structural variation between the wild type and the mutantprotein structures.
Abstract: The T118M mutation in PMP22 gene is associated with Charcot Marie Tooth, type 1A (CMT1A). CMT1A is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Mutations in CMT related disorder are seen to increase the stability of the protein resulting in the diseased state. We performed SNP analysis for all the nsSNPs of PMP22 protein and carried out molecular dynamics simulation for T118M mutation to compare the stability difference between the wild type protein structure and the mutant protein structure. The mutation T118M resulted in the overall increase in the stability of the mutant protein. The superimposed structure shows marked structural variation between the wild type and the mutant protein structures.

84 citations

Journal ArticleDOI
TL;DR: It is demonstrated that potential β-lactam antibiotics can efficiently bind to different types of PBPs for circumventing β- lactam resistance and opens avenues for the development of newer antibiotics that can target bacterial pathogens.
Abstract: Bacterial resistance to β-lactam antibiotics poses a serious threat to human health. Penicillin binding proteins (PBPs) and β-lactamases are involved in both antibacterial activity and mediation of β-lactam antibiotic resistance. The two major reasons for resistance to β-lactams include: (i) pathogenic bacteria expressing drug insensitive PBPs rendering β-lactam antibiotics ineffective and (ii) production of β-lactamases along with alteration of their specificities. Thus, there is an urgent need to develop newer β-lactams to overcome the challenge of bacterial resistance. Therefore the present study aims to identify the binding affinity of β-lactam antibiotics with different types of PBPs and β-lactamases. In this study, cephalosporins and carbapenems are docked into PBP2a of Staphylococcus aureus, PBP2b and PBP2x of Streptococcus pneumoniae and SHV-1 β-lactamase of Escherichia coli. The results reveal that Ceftobiprole can efficiently bind to PBP2a, PBP2b and PBP2x and not strongly to SHV-1 β-lactamase. Furthermore, molecular dynamics (MD) simulations are performed to refine the binding mode of the docked complex structure and to observe the differences in the stability of free PBP2x and Ceftobiprole bound PBP2x. MD simulation supports the greater stability of the Ceftobiprole–PBP2x complex compared to free PBP2x. This work demonstrates that potential β-lactam antibiotics can efficiently bind to different types of PBPs for circumventing β-lactam resistance and opens avenues for the development of newer antibiotics that can target bacterial pathogens.

62 citations

Journal ArticleDOI
10 Jan 2016-Gene
TL;DR: A model based on protein/gene network is proposed to identify genes/proteins associated with drug resistance in S. aureus and reveals many associated antibiotic resistant genes and proteins and their role in resistance mechanisms.

55 citations


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[...]

08 Dec 2001-BMJ
TL;DR: There is, I think, something ethereal about i —the square root of minus one, which seems an odd beast at that time—an intruder hovering on the edge of reality.
Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

33,785 citations

01 Aug 2000
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

4,833 citations

Journal ArticleDOI
TL;DR: It is concluded that molecular typing of coagulase-negative staphylococci from blood cultures does not correlate with clinical criteria for true bacteremia, suggesting either that true bactseremias are frequently the result of multiple strains or that the commonly used clinical criteria are not accurate for distinguishing contamination from true b acteremia.
Abstract: of antibiotics, whether there was an explicit note in the medical chart in which the physician diagnosed a true bacteremia, and the Centers for Disease Control surveillance criteria for primary bloodstream infection. Agreement between same-strain bacteremia and each definition was examined, based on the assumption that most true infections should be the result of a single strain. The study sample consisted of 42 patients and 106 isolates. Nineteen of the 42 bacteremias (45%) were the same strain. Classification of bacteremias as same-strain correlated poorly with all three clinical assessments (range of percentage agreement, 50%-57%; range of kappa statistic, 0.01-0.15). There were both false-positive and false-negative errors. Patients with three or more positive blood cultures were more likely to have same-strain bacteremia than those with only two positive cultures (11/15 [73%] vs 8/27 [30%], P=.006). Pulsed-field gel electrophoresis was more discriminating than AP PCR (percentage agreement, 83%; kappa, 0.67). The authors concluded that molecular typing correlated poorly with clinical criteria for true bacteremia, suggesting either that true bacteremias are frequently the result of multiple strains or that the commonly used clinical criteria are not accurate for distinguishing contamination from true bacteremia. Vancomycin treatment of clinically defined coagulase-negative staphylococcal bacteremia may frequently be unnecessary. FROM: Seo SK, Venkataraman L, DeGirolami PC, Samore MH. Molecular typing of coagulase-negative staphylococci from blood cultures does not correlate with clinical criteria for true bacteremia. Am J Med 2000;109:697-704.

1,073 citations

Journal ArticleDOI
TL;DR: The physical nature of σ- and π-hole interactions is described, a selection of inquiries that utilise ρ- andπ-holes are presented, and an overview of analyses of structural databases (CSD/PDB) that demonstrate how prevalent these interactions already are in solid-state structures are given.
Abstract: Non-covalent interactions play a crucial role in (supramolecular) chemistry and much of biology. Supramolecular forces can indeed determine the structure and function of a host–guest system. Many sensors, for example, rely on reversible bonding with the analyte. Natural machineries also often have a significant non-covalent component (e.g. protein folding, recognition) and rational interference in such ‘living’ devices can have pharmacological implications. For the rational design/tweaking of supramolecular systems it is helpful to know what supramolecular synthons are available and to understand the forces that make these synthons stick to one another. In this review we focus on σ-hole and π-hole interactions. A σ- or π-hole can be seen as positive electrostatic potential on unpopulated σ* or π(*) orbitals, which are thus capable of interacting with some electron dense region. A σ-hole is typically located along the vector of a covalent bond such as XH or XHlg (X=any atom, Hlg=halogen), which are respectively known as hydrogen and halogen bond donors. Only recently it has become clear that σ-holes can also be found along a covalent bond with chalcogen (XCh), pnictogen (XPn) and tetrel (XTr) atoms. Interactions with these synthons are named chalcogen, pnigtogen and tetrel interactions. A π-hole is typically located perpendicular to the molecular framework of diatomic π-systems such as carbonyls, or conjugated π-systems such as hexafluorobenzene. Anion–π and lone-pair–π interactions are examples of named π-hole interactions between conjugated π-systems and anions or lone-pair electrons respectively. While the above nomenclature indicates the distinct chemical identity of the supramolecular synthon acting as Lewis acid, it is worth stressing that the underlying physics is very similar. This implies that interactions that are now not so well-established might turn out to be equally useful as conventional hydrogen and halogen bonds. In summary, we describe the physical nature of σ- and π-hole interactions, present a selection of inquiries that utilise σ- and π-holes, and give an overview of analyses of structural databases (CSD/PDB) that demonstrate how prevalent these interactions already are in solid-state structures.

501 citations

Journal ArticleDOI
11 Sep 2018-JAMA
TL;DR: Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality, and findings do not support use of piperACillin- tazobactsam in this setting.
Abstract: Importance Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective “carbapenem-sparing” option to treat extended-spectrum β-lactamase producers. Objectives To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae . Design, Setting, and Participants Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study. Interventions Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician. Main Outcomes and Measures The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used. Results Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, −∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group. Conclusions and relevance Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting. Trial Registration anzctr.org.au Identifiers:ACTRN12613000532707andACTRN12615000403538and ClinicalTrials.gov Identifier:NCT02176122

487 citations