Docking-based virtual screening of known drugs against murE of Mycobacterium tuberculosis towards repurposing for TB.

Repurposing has gained momentum globally and become an alternative avenue for drug discovery because of its better success rate, and reduced cost, time and issues related to safety than the conventional drug discovery process. Several drugs have already been successfully repurposed for other clinical conditions including drug resistant tuberculosis (DR-TB). Though TB can be cured completely with the use of currently available anti-tubercular drugs, emergence of drug resistant strains of Mycobacterium tuberculosis and the huge death toll globally, together necessitate urgently newer and effective drugs for TB. Therefore, we performed virtual screening of 1554 FDA approved drugs against murE, which is essential for peptidoglycan biosynthesis of M. tuberculosis. We used Glide and AutoDock Vina for virtual screening and applied rigid docking algorithm followed by induced fit docking algorithm in order to enhance the quality of the docking prediction and to prioritize drugs for repurposing. We found 17 drugs binding strongly with murE and three of them, namely, lymecycline, acarbose and desmopressin were consistently present within top 10 ranks by both Glide and AutoDock Vina in the induced fit docking algorithm, which strongly indicates that these three drugs are potential candidates for further studies towards repurposing for TB

A study on prevalence and co-morbidity of bipolar and anxiety disorders in chronic headache patients

Background: Co morbidity between headache and psychiatric disorders is more prevalent in chronic headache patients. The bipolar disorders and anxiety disorders are predominant in migraine and TTH respectively. This co morbidities have a poor reflection and impact on quality and outcome of chronic headache patients and results in worst prognosis and poor response to medical treatment.Methods: The chronic headache patients especially migraine and tension type of headache were analyzed with following materials such as the structured psychiatric clinical interview with ICD-10 mental and behavioural disorder, DSM-5 criteria. HAM-A, HAM-D, BDI-2, BPRS, young mania rating scale, Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and panic disorder scale.Results: Various subsets of bipolar disorder and anxiety disorder were found as follows: 74% of migraineurs are associated with psychiatric disorders in which bipolar affective disorder 6%, depressive episode 48%, dysthymia 30%, GAD 10% and Panic disorder 6%. 52% of TTH are associated with psychiatric disorders as follows: major depressive episode 52%, GAD 30%, separation anxiety disorder 6%, PTSD 7%, OCD 3% and panic disorder 2%.Conclusions: From previous and future studies the headache can be identified according to subsets of headache with psychiatric disorders make easier to provide appropriate pharmacological and psychological treatment which may reduce the chronicity and intractability of headache

Molecular docking of azole drugs and their analogs on CYP121 of Mycobacterium tuberculosis

The Mycobacterium tuberculosis genome codes for 20 different cytochromes. These cytochromes are involved in the breakdown of recalcitrant pollutants and the synthesis of polyketide antibiotics and other complex macromolecules. It has been demonstrated that CYP121 is essential for viability of the bacterium by gene knock-out and complementation studies. CYP121 could therefore be a probable target for the development of new drugs for TB. It has been widely reported that orthologs of CYP121 in fungi are inhibited by azole drugs. We evaluated whether these azole drugs or their structural analogs could bind to and inhibit CYP121 of M. tuberculosis using molecular docking. Six molecules with known anti-CYP121 activity were selected from literature and PubChem database was searched to identify structural analogs for these inhibitors. Three hundred and fifty seven molecules were identified as structural analogs and used in docking studies. Fifty three molecules were found to be scored better than the azole drugs and five of them were ranked among the top 12 molecules by two different scoring functions. These molecules may be further tested by in vitro experimentation for their activity against CYP121 of M. tuberculosis

FUNCTIONAL CHARACTERIZATION OF gnb3b AND guk1b FOR PHOTORECEPTOR INTEGRITY IN A ZEBRAFISH MODEL FOR RETINITIS PIGMENTOSA

Ph.DDOCTOR OF PHILOSOPH

A study on prevalence of various mood disorders in patients with multiple sclerosis in South Indian population Chennai, Tamil Nadu

Background: The prevalence of depressive disorders are more common in demyelination diseases like multiple sclerosis. Patients with multiple sclerosis have higher rates of depressive episodes than the general population. It is found that 40-50% incidence reported in many number of previous research studies .The aim is to study the prevalence of various depressive disorders in multiple sclerosis (MS) patient population.Methods: 176 MS patients were randomly selected from neurology outpatient department (OPD) of Tamil Nadu Government Multi Super Specialty Hospital and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, from September 2018 to December 2019. 128 patients were analyzed with the following methods of examinations such as the structured psychiatric clinical interview with diagnostic and statistical manual of mental disorders (DSM)-5 and international classification of diseases (ICD)-10 criteria, Hamilton depression rating scale (HAM-D) scale.Results: Various subtypes of mood disorders were found as follows major depressive disorder (MDD)-4%, MDD with anxiety-6%, pervasive developmental disorders (PDD) mixed-4%, premenstrual dysphoric disorder (PMDD)-8%, MIDD-2% and depressive disorders due to general medical conditions (secondary depression)-22%. In this present study 46% of the MS population were diagnosed with various depressive illness.Conclusions: Early identification and treatment of depressive disorders definitely favour the outcome of MS patients. The coping skills and good social support system play a vital role in the outcome of depressive disorders in MS population in addition to psychopharmacological management.

Current standards and ethical landscape of engineered tissues—3D bioprinting perspective

Tissue engineering is an evolving multi-disciplinary field with cutting-edge technologies and innovative scientific perceptions that promise functional regeneration of damaged tissues/organs. Tissue engineered medical products (TEMPs) are biomaterial-cell products or a cell-drug combination which is injected, implanted or topically applied in the course of a therapeutic or diagnostic procedure. Current tissue engineering strategies aim at 3D printing/bioprinting that uses cells and polymers to construct living tissues/organs in a layer-by-layer fashion with high 3D precision. However, unlike conventional drugs or therapeutics, TEMPs and 3D bioprinted tissues are novel therapeutics and need different regulatory protocols for clinical trials and commercialization processes. Therefore, it is essential to understand the complexity of raw materials, cellular components, and manufacturing procedures to establish standards that can help to translate these products from bench to bedside. These complexities are reflected in the regulations and standards that are globally in practice to prevent any compromise or undue risks to patients. This review comprehensively describes the current legislations, standards for TEMPs with a special emphasis on 3D bioprinted tissues. Based on these overviews, challenges in the clinical translation of TEMPs & 3D bioprinted tissues/organs along with their ethical concerns and future perspectives are discussed

Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals.

Broadly Cross clade Neutralizing (BCN) antibodies are recognized as potential therapeutic tools and leads for the design of a vaccine that can protect human beings against various clades of Human Immunodeficiency Virus (HIV). In the present study, we screened plasma of 88 HIV-1 infected ART naïve individuals for their neutralization potential using a standard panel of 18 pseudoviruses belonging to different subtypes and different levels of neutralization. We identified 12 samples with good breadth of neutralization (neutralized >90% of the viruses). Four of these samples neutralized even the difficult-to-neutralize tier-3 pseudoviruses with great potency (GMT > 600). Analysis of neutralization specificities indicated that four samples had antibodies with multiple epitope binding specificities, viz. CD4-binding site (CD4BS), glycans in the V1/V2 and V3 regions and membrane proximal external region (MPER). Our findings indicate the strong possibility of identifying highly potent bNAbs with known or novel specificities from HIV-1 subtype C infected individuals from India that can be exploited as therapeutic tools or lead molecules for the identification of potential epitopes for design of a protective HIV-1 vaccine

Current standards and ethical landscape of engineered tissues—3D bioprinting perspective

Tissue engineering is an evolving multi-disciplinary field with cutting-edge technologies and innovative scientific perceptions that promise functional regeneration of damaged tissues/organs. Tissue engineered medical products (TEMPs) are biomaterial-cell products or a cell-drug combination which is injected, implanted or topically applied in the course of a therapeutic or diagnostic procedure. Current tissue engineering strategies aim at 3D printing/bioprinting that uses cells and polymers to construct living tissues/organs in a layer-by-layer fashion with high 3D precision. However, unlike conventional drugs or therapeutics, TEMPs and 3D bioprinted tissues are novel therapeutics and need different regulatory protocols for clinical trials and commercialization processes. Therefore, it is essential to understand the complexity of raw materials, cellular components, and manufacturing procedures to establish standards that can help to translate these products from bench to bedside. These complexities are reflected in the regulations and standards that are globally in practice to prevent any compromise or undue risks to patients. This review comprehensively describes the current legislations, standards for TEMPs with a special emphasis on 3D bioprinted tissues. Based on these overviews, challenges in the clinical translation of TEMPs & 3D bioprinted tissues/organs along with their ethical concerns and future perspectives are discussed