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Dengue Virus (DENV) is a serious threat to human life worldwide and is one of the most dangerous vector-borne diseases, causing thousands of deaths annually. We constructed a comprehensive PPI map of DENV with its host Homo sapiens and performed various bioinformatics analyses. We found 1195 interactions between 858 human and 10 DENV proteins. Pathway enrichment analysis was performed on the two sets of gene products, and the top 5 human proteins with the maximum number of interactions with dengue viral proteins revealed noticeable results. The non-structural protein NS1 in DENV had the maximum number of interactions with the host protein, followed by NS5 and NS3. Among the human proteins, HBA1 and UBE2I were associated with 7 viral proteins, and 3 human proteins (CSNK2A1, RRP12, and HSP90AB1) were found to interact with 6 viral proteins. Pharmacophore-based virtual screening of millions of compounds in the public databases was performed to identify potential DENV-NS1 inhibitors. The lead compounds were selected based on RMSD values, docking scores, and strong binding affinities. The top ten hit compounds were subjected to ADME profiling which identified compounds C2 (MolPort-044-180-163) and C6 (MolPort-001-742-737) as lead inhibitors against DENV-NS1. Molecular dynamics trajectory analysis and intermolecular interactions between NS1 and the ligands displayed the molecular stability of the complexes in the cellular environment. The in-silico approaches used in this study could pave the way for the development of potential specie-specific drugs and help in eliminating deadly viral infections. Therefore, experimental and clinical assays are required to validate the results of this study. [ABSTRACT FROM AUTHOR]

Moraxella catarrhalis (M. catarrhalis) is a gram-negative bacterium, responsible for major respiratory tract and middle ear infection in infants and adults. The recent emergence of the antibiotic resistance M. catarrhalis demands the prioritization of an effective drug target as a top priority. Fortunately, the failure of new drugs and host toxicity associated with traditional drug development approaches can be avoided by using an in silico subtractive genomics approach. In the current study, the advanced in silico genome subtraction approach was applied to identify potential and pathogen-specific drug targets against M. catarrhalis. We applied a series of subtraction methods from the whole genome of pathogen based on certain steps i.e. paralogous protein that have extensive homology with humans, essential, drug like, non-virulent, and resistant proteins. Only 38 potent drug targets were identified in this study. Eventually, one protein was identified as a potential new drug target and forwarded to the structure-based studies i.e. histidine kinase (UniProt ID: D5VAF6). Furthermore, virtual screening of 2000 compounds from the ZINC database was performed against the histidine kinase that resulted in the shortlisting of three compounds as the potential therapeutic candidates based on their binding energies and the properties exhibited using ADMET analysis. The identified protein gives a platform for the discovery of a lead drug candidate that may inhibit it and may help to eradicate the otitis media caused by drug-resistant M. catarrhalis. Nevertheless, the current study helped in creating a pipeline for drug target identification that may assist wet-lab research in the future. [ABSTRACT FROM AUTHOR]

Background: Suicide is a serious public health concern all over the world including Bangladesh. About 9% of the patients admitted with suicidal ideation (SI) or suicide attempt (SA) later complete suicide. To understand and prevent suicide, the study of SI and SA is necessary but research in this area is scanty in Bangladesh. Therefore, we studied suicidality (SI and SA) among married adults in Rajshahi City, Bangladesh. Methods: This was a household cross-sectional study. A total of 708 married adults were selected for this study using a multi-stage random sampling. Suicidality was measured based on two factors: (i) suicidal ideation, and (ii) suicide attempt. Frequency distribution, Chi-square test and multiple binary logistic regression model were used in this study according to our objectives. Results: The prevalence of suicidal ideation, suicide attempt, and suicidality was 5.8%, 3.4%, and 8.3% respectively among married adults. A multiple binary logistic regression model provided the following risk factors of suicidality: (i) joint family (AOR = 0.310, p<0.01), (ii) ≥26 years of age at the first marriage (AOR = 0.379, p<0.05), (iii) twice or more marriage (AOR = 0.214, p<0.01), (iv) conjugal life of ≥16 years (AOR = 0.410, p<0.05), (v) having no child (AOR = 6.343, p<0.01) and (vi) having 1–2 children (AOR = 6.190, p<0.01), (vii) medical comorbidity (AOR = 0.421, p<0.01), (viii) mental comorbidity (AOR = 0.253, p<0.01), (ix) stress-anxiety (AOR = 0.311, p<0.01), (x) family history of mental disorders (AOR = 0.059, p<0.01), (xi) family history of suicide/suicide attempt (AOR = 0.009, p<0.01), (xii) substance abuse (AOR = 0.065, p<0.01), (xiii) poor relationship with spouse (AOR = 0.209, p<0.01), and (xiv) poor relationship with other family members (AOR = 0.347, p<0.05). Conclusion: The prevalence of suicidality is remarkable in Rajshahi city, Bangladesh. The government and non-government agencies can use the findings of this study to identify the vulnerable groups and undertake measures for preventing and reducing suicidality. [ABSTRACT FROM AUTHOR]

Backgrounds: Approximately, half of the population in the world including tropical and sub-tropical climates region is at risk of dengue. Being an endemic country, Bangladesh has experienced the largest dengue epidemic in 2019. The present study aimed at evaluating the clinical and laboratory profile of dengue patients in northern Bangladesh during the epidemic. Methods: This cross-sectional study included 319 serologically confirmed dengue patients admitted in Shaheed Ziaur Rahman Medical College Hospital in Bogra district. It is one of the main tertiary care hospitals in northern Bangladesh. Data were collected from July to September 2019. Patients' clinical and laboratory data were extracted from clinical records. Patients were classified into two classes according to the WHO 2009 dengue classification such as (i) non-severe dengue and (ii) severe dengue. Chi-square test and independent t-test were used in this study. Results: Of the 319 patients, 94.1% had non-severe dengue and the remaining 5.9% had severe dengue (severe plasma leakage 68.4%, severe organ involvement 68.4%, and severe clinical bleeding 10.5%). Most of the patients were suffering from primary dengue infection. The most common clinical presentation was fever followed by headache and myalgia. Vomiting and abdominal pain were the most prevalent warning signs. The common hematological findings on admission were leukopenia (63.3%), thrombocytopenia (30.4%) and increased hematocrit (26.6%). Raised serum ALT or AST was observed in 14.1% cases whereas raised serum creatinine was observed in 6.6% cases. Signs of plasma leakage (pleural effusion, respiratory distress, and ascites, rise of hematocrit >20% during hospital stay) and hepatic or renal involvement (serum ALT >42UI/L or serum creatinine >1.2 mg/dL) on admission were mostly associated with severe dengue. Conclusion: The study provides clinical evidence on presentation as well as hematological and biochemical profile of dengue patients in northern Bangladesh that should be implicated in effective patient management. Author summary: Dengue has become a significant public health concern worldwide in recent years especially for the South-East Asian, sub-Saharan African and Latin American countries. Bangladesh has experienced a number of outbreaks of dengue, the largest one occurred in 2019. Management of dengue cases during an epidemic is a major challenge for a limited resource country like Bangladesh. To predict the risk of developing severe dengue a combined evaluation of early symptoms and laboratory test profiles is necessary. Despite the fact, there is a lack of evidence of clinical and laboratory parameters of dengue patients in Bangladesh. Authors wanted to highlight the clinical features, and hematological and biochemical profiles of dengue patients diagnosed in Bogra district, a non-endemic zone situated in northern Bangladesh. The authors reported that fever, headache, and myalgia were the commonest presenting complaints of dengue patients whereas vomiting and abdominal pain was the most prevalent warning signs. Severe dengue was associated mostly with plasma leakage rather than hemorrhage and the rise of hematocrit during hospital stay was a predictor of severe dengue. These findings will guide physicians for prompt therapeutic management of dengue infection in the study area. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is an alarming and growing threat to public health. The present treatment gives limited efficacy and is poorly tolerated, recommending the urgent medical demand for novel therapeutics. NS3/4A protease is a significant emerging target for the treatment of HCV infection. This work reports the complex-based pharmacophore modeling to find out the important pharmacophoric features essential for the inhibition of both protease and helicase activity of NS3/4A protein of HCV. A seven featured pharmacophore model of HCV NS3/4A protease was developed from the crystal structure of NS3/4A protease in complex with a macrocyclic inhibitor interacting with both protease and helicase sites residues via MOE pharmacophore constructing tool. It consists of four hydrogen bond acceptors (Acc), one hydrophobic (Hyd), one for lone pair or active hydrogen (Atom L) and a heavy atom feature (Atom Q). The generated pharmacophore model was validated by a test database of seventy known inhibitors containing 55 active and 15 inactive/least active compounds. The validated pharmacophore model was used to virtually screen the ChemBridge database. As a result of screening 1009 hits were retrieved and were subjected to filtering by Lipinski’s rule of five on the basis of which 786 hits were selected for further assessment using molecular docking studies. Finally, 15 hits of different scaffolds having interactions with important active site residues were predicted as lead candidates. These candidates having unique scaffolds have a strong likelihood to act as further starting points in the development of novel and potent NS3/4A protease inhibitors. [ABSTRACT FROM AUTHOR]

Membrane fusion is the central molecular event during the entry of enveloped viruses into cells. The critical agents of this process are viral surface proteins, primed to facilitate cell bilayer fusion. The important role of Dendritic-cell-specific ICAM3-grabbing non-integrin (DC-SIGN) in Dengue virus transmission makes it an attractive target to interfere with Dengue virus Propagation. Receptor mediated endocytosis allows the entry of virions due to the presence of endosomal membranes and low pH-induced fusion of the virus. DC-SIGN is the best characterized molecule among the candidate protein receptors and is able to mediate infection with the four serotypes of dengue virus (DENV). Unrestrained pair wise docking was used for the interaction of dengue envelope protein with DC-SIGN and monoclonal antibody 2G12. Pre-processed the PDB coordinates of dengue envelope glycoprotein and other candidate proteins were prepared and energy minimized through AMBER99 force field distributed in MOE software. Protein-protein interaction server, ZDOCK was used to find molecular interaction among the candidate proteins. Based on these interactions it was found that antibody successfully blocks the glycosylation site ASN 67 and other conserved residues present at DC-SIGN-Den-E complex interface. In order to know for certain, the exact location of the antibody in the envelope protein, co-crystallize of the envelope protein with these compounds is needed so that their exact docking locations can be identified with respect to our results. [ABSTRACT FROM AUTHOR]