Md. Salimullah

Treating Diabetes Mellitus: Pharmacophore Based Designing of Potential Drugs from Gymnema sylvestre against Insulin Receptor Protein.

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders which can affect the quality of life severely. Injectable insulin is currently being used to treat DM which is mainly associated with patient inconvenience. Small molecules that can act as insulin receptor (IR) agonist would be better alternatives to insulin injection. Herein, ten bioactive small compounds derived from Gymnema sylvestre (G. sylvestre) were chosen to determine their IR binding affinity and ADMET properties using a combined approach of molecular docking study and computational pharmacokinetic elucidation. Designing structural analogues were also performed for the compounds associated with toxicity and less IR affinity. Among the ten parent compounds, six were found to have significant pharmacokinetic properties with considerable binding affinity towards IR while four compounds were associated with toxicity and less IR affinity. Among the forty structural analogues, four compounds demonstrated considerably increased binding affinity towards IR and less toxicity compared with parent compounds. Finally, molecular interaction analysis revealed that six parent compounds and four analogues interact with the active site amino acids of IR. So this study would be a way to identify new therapeutics and alternatives to insulin for diabetic patients.

Therapeutics Insight with Inclusive Immunopharmacology Explication of Human Rotavirus A for the Treatment of Diarrhea

Rotavirus is the most common cause of severe infant and childhood diarrhea worldwide, and the morbidity and mortality rate is going to be outnumbered in developing countries like Bangladesh. To mitigate this substantial burden of disease, new therapeutics such as vaccine and drug are swiftly required against rotavirus. The present therapeutics insight study was performed with comprehensive immunoinformatics and pharmacoinformatics approach. T and B-cell epitopes were assessed in the conserved region of outer capsid protein VP4 among the highly reviewed strains from different countries including Bangladesh. The results suggest that epitope SU1 (TLKNLNDNY) could be an ideal candidate among the predicted five epitopes for both T and B-cell epitopes for the development of universal vaccine against rotavirus. This research also suggests five novel drug compounds from medicinal plant Rhizophora mucronata Lamk. for better therapeutics strategies against rotavirus diarrhea based on 3D structure building, pharmacophore, ADMET, and QSAR properties. The exact mode of action between drug compounds and target protein VP4 were revealed by molecular docking analysis. Drug likeness and oral bioavailability further confirmed the effectiveness of the proposed drugs against rotavirus diarrhea. This study might be implemented for experimental validation to facilitate the novel vaccine and drug design.

Complete Genome Sequence of a Circulating Hepatitis B Virus Genotype C Strain Isolated from a Chronically Infected Patient Identified at an Outdoor Hospital in Bangladesh

ABSTRACT Hepatitis B virus (HBV) causes significant global health problems despite the presence of a potential vaccine. HBV chronic cases are increasing rapidly in developing countries like Bangladesh. Here, we report the complete genome sequence of an HBV genotype C strain isolated from a chronic patient identified at an outdoor hospital section.

Identification of a novel tri-genotypic recombinant Hepatitis B virus in Bangladesh

We report a novel tri-genotypic recombinant Hepatitis B virus (HBV) strain circulating in Bangladesh. The strain is recombinant with the genotypes D, C and E, of which, genotype E was not reported before in Bangladesh. Additionally, the complete genome has a frameshift deletion of nine nucleotides from overlapping Surface and Polymerase genes, and a vaccine escape mutation, A128 V, in the surface protein. This is the first report with such unusual recombination event responsible for rapid liver cirrhosis in a 13 year old patient in Bangladesh. This report may alert the clinicians to take the measure to prevent an upcoming outbreak of recombinant HBV.

Towards finding the linkage between metabolic and age-related disorders using semantic gene data network analysis.

A metabolic disorder (MD) occurs when the metabolic process is disturbed. This process is carried out by thousands of enzymes participating in numerous inter-dependent metabolic pathways. Critical biochemical reactions that involve the processing and transportation of carbohydrates, proteins and lipids are affected in metabolic diseases. Therefore, it is of interest to identify the common pathways of metabolic disorders by building protein-protein interactions (PPI) for network analysis. The molecular network linkages between MD and age related diseases (ARD) are intriguing. Hence, we created networks of protein-protein interactions that are related with MD and ARD using relevant known data in the public domain. The network analysis identified known MD associated proteins and predicted genes and or its products of ARD in common pathways. The genes in the common pathways were isolated from the network and further analyzed for their co-localization and shared domains. Thus, a model hypothesis is proposed using interaction networks that are linked between MD and ARD. This data even if less conclusive finds application in understanding the molecular mechanism of known diseases in relation to observed molecular events

Analysis of the complete genome of hepatitis B virus subgenotype C2 isolate NHB17965 from a patient with uncomplicated chronicity

The number of chronic cases of hepatitis B virus (HBV) is increasing rapidly in the world. Herein, we report a complete genome of HBV subgenotype C2 (HBV/C2) with current common amino acid substitutions from a patient with chronic HBV without liver complications. Complete genome analysis revealed that the isolated strain was a non-recombinant wild type and had several regular substitutions in the reverse transcriptase domain and small surface proteins of HBV. The isolated complete sequence could be considered as a chronic reference strain of HBV/C2 in Bangladesh. This study may help clinicians and scientists gain in-depth knowledge on common substitutions of HBV/C2 genome and to identify potential therapies against chronic HBV infections.

Analysis of the complete genome of hepatitis B virus subgenotype C2 isolate NHB17965 from a HBV infected patient

The burden of chronic hepatitis B virus (HBV) infections is increasingly detected nowadays. Herein, we report a complete genome of HBV subgenotype C2 (HBV/C2) from a HBV infected patient. Complete genome analysis revealed that the isolated strain was a non-recombinant wild type and had several regular substitutions in the reverse transcriptase domain and small surface proteins of HBV. This study may help clinicians and scientists gain in-depth knowledge on the current substitutions of HBV/C2 genome and to identify potential therapies against HBV infections.

Molecular evolution and genomics of hepatitis B virus subgenotype C2 strain predominant in the chronic patients in Bangladesh

Evolution of hepatitis B virus (HBV) is a mystery and caused mainly by genomic mutations as well as recombination. Viral evolution may be responsible for increasing disease severity and render resistance to the existing treatment processes. HBV/C2 strain is associated with chronicity, which may progress to the liver cirrhosis and hepatocellular carcinoma. Furthermore, HBV/C2 strain is highly prevalent in the chronic hepatitis B patients in Bangladesh. Hence, the molecular evolution of that strain and its disease pattern need to be uncovered. Herein, the purpose of this study is to determine the potential mutations of HBV complete genome sequences isolated in Bangladesh and the molecular evolution of HBV/C2 strain. Mutation analysis of the total 57 complete genome sequences of HBV in Bangladesh revealed that 42.11%, 12.28%, 7.02% and 3.51% of the strains were vaccine resistant, HBsAg detection escape, HBV immunoglobulin escape, multi-drug resistant respectively. Furthermore, of the vaccine resistant strains, 16.67% were observed resistant to both vaccine, HBsAg detection and immunoglobulin escape. Bayesian skyline analysis with 462 HBV/C2 strains from 2000 to 2017 revealed the evolution of the strain was in nineteenth century with two rapid sharp increases in the genetic diversity at the end of the twentieth century and then a sudden decrease in the early twenty-first century as observed in C and X gene analysis. This study may help researchers and clinicians to get a better knowledge about the emergence and evolution of HBV/C2 strain that may help to find a proper treatment strategy against hepatitis B.

Pathway based therapeutic targets identification and development of an interactive database CampyNIBase of Campylobacter jejuni RM1221 through non-redundant protein dataset

The bacterial species Campylobacter jejuni RM1221 (CjR) is the primary cause of campylobacteriosis which poses a global threat for human health. Over the years the efficacy of antibiotic treatment is becoming more fruitless due to the development of multiple drug resistant strains. Therefore, identification of new drug targets is a valuable tool for the development of new treatments for affected patients and can be obtained by targeting essential protein(s) of CjR. We conducted this in silico study in order to identify therapeutic targets by subtractive CjR proteome analysis. The most important proteins of the CjR proteome, which includes chokepoint enzymes, plasmid, virulence and antibiotic resistant proteins were annotated and subjected to subtractive analyses to filter out the CjR essential proteins from duplicate or human homologous proteins. Through the subtractive and characterization analysis we have identified 38 eligible therapeutic targets including 1 potential vaccine target. Also, 12 potential targets were found in interactive network, 5 targets to be dealt with FDA approved drugs and one pathway as potential pathway based drug target. In addition, a comprehensive database ‘CampyNIBase’ has also been developed. Besides the results of this study, the database is enriched with other information such as 3D models of the identified targets, experimental structures and Expressed Sequence Tag (EST) sequences. This study, including the database might be exploited for future research and the identification of effective therapeutics against campylobacteriosis. URL: (http://nib.portal.gov.bd/site/page/4516e965-8935-4129-8c3f-df95e754c562#Banner).

An immunopharmacoinformatics approach in development of vaccine and drug candidates for West Nile virus

An outbreak of West Nile Virus (WNV) like the recent Ebola can be more epidemic and fatal to public health throughout the world. WNV possesses utmost threat as no vaccine or drug is currently available for its treatment except mosquito control. The current study applied the combined approach of immunoinformatics and pharmacoinformatics to design potential epitope-based vaccines and drug candidates against WNV. By analyzing the whole proteome of 2994 proteins, the WNV envelope glycoprotein was selected as a therapeutic target based on its highest antigenicity. After proper assessment “KSFLVHREW” and “ITPSAPSYT” were found to be the most potential T and B-cell epitopes, respectively. Besides, we have designed and validated four novel drugs from a known WNV inhibitor, AP30451 by adopting computational approaches. Toxicity assessment and drug score confirmed the effectiveness of these drug candidates. This in silico research might greatly facilitate the wet lab experiments to develop vaccine and drug against WNV.