Development and characterization of new peptidomimetic inhibitors of the West Nile virus NS2B-NS3 protease

Potent inhibitors of the West Nile virus NS2B-NS3 protease could be useful drugs for the treatment of WNV infections. Therefore, in the present work, new substrate analogue inhibitors against the WNV protease have been developed. In this present work, new decarboxylated arginine memtics inhibitors against the WNV NS2B-NS3 protease were developed. In comparison to the known agmatine derivatives, the P1 trans-4-Guanidinocyclohexylmethylamid containing inhibitors have higher potency and selectivity against the WNV. Moreover, the first crystal structure of the WNV protease in complex with small noncovalently-binding inhibitor was solved

Conductance of S-Alkylisothiouronium Iodides in Methanol at 25° C

Equivalent conductivities are reported for S-Methyl-, S-n- . -Butyl, S-n-Amyl- and S-n-Heptylisothiouronium iodides in methanol (D = 32.63) at 25 °c. The data were analyzed by the Fuoss-Onsager equation for 1 : 1 associated electrolytes. The characteristic constants: the equivalent conductance at infinite dilution A0 , the closest approach distance a0 and the association constant KA are · derived

Young Adult with Canon Ball Lung Metastasis and Unknown Primary: A Case of Primary Pulmonary Myxoid Sarcoma

Extra skeletal Myxoid Chondrosarcoma (EMC) is a rare soft tissue sarcoma, which primarily occurs deep in extremities, especially in the skeletal muscle or tendon. Unusual locations include tongue, retroperitoneum, spine, intracranium, testis, inguinal region, synovium, mammary gland, labium and pleura, however no case of has been described the aggressive involvement of lung with multiple canon ball metastatic atypical chondromyxoid neoplasm with unknown primary. We hereby present a 38 year old Asian male patient initially presented for cough and occasional blood stained sputum with chest pain since few days, found to have multiple canon ball lung lesions which histopathological suggestive of atypical chondromyxoidnbsp sarcoma and primary source remained to be unknown. nbs

A Health Systems Approach to Integrated Community Case Management of Childhood Illness: Methods and Tools

Integrated community case management (iCCM) of childhood illness is an increasingly popular strategy to expand life-saving health services to underserved communities. However, community health approaches vary widely across countries and do not always distribute resources evenly across local health systems. We present a harmonized framework, developed through interagency consultation and review, which supports the design of CCM by using a systems approach. To verify that the framework produces results, we also suggest a list of complementary indicators, including nine global metrics, and a menu of 39 country-specific measures. When used by program managers and evaluators, we propose that the framework and indicators can facilitate the design, implementation, and evaluation of community case management

Illustrating and homology modeling the proteins of the Zika virus

The Zika virus (ZIKV) is a flavivirus of the family Flaviviridae, which is similar to dengue virus, yellow fever and West Nile virus. Recent outbreaks in South America, Latin America, the Caribbean and in particular Brazil have led to concern for the spread of the disease and potential to cause Guillain-Barré syndrome and microcephaly. Although ZIKV has been known of for over 60 years there is very little in the way of knowledge of the virus with few publications and no crystal structures. No antivirals have been tested against it either in vitro or in vivo. ZIKV therefore epitomizes a neglected disease. Several suggested steps have been proposed which could be taken to initiate ZIKV antiviral drug discovery using both high throughput screens as well as structure-based design based on homology models for the key proteins. We now describe preliminary homology models created for NS5, FtsJ, NS4B, NS4A, HELICc, DEXDc, peptidase S7, NS2B, NS2A, NS1, E stem, glycoprotein M, propeptide, capsid and glycoprotein E using SWISS-MODEL. Eleven out of 15 models pass our model quality criteria for their further use. While a ZIKV glycoprotein E homology model was initially described in the immature conformation as a trimer, we now describe the mature dimer conformer which allowed the construction of an illustration of the complete virion. By comparing illustrations of ZIKV based on this new homology model and the dengue virus crystal structure we propose potential differences that could be exploited for antiviral and vaccine design. The prediction of sites for glycosylation on this protein may also be useful in this regard. While we await a cryo-EM structure of ZIKV and eventual crystal structures of the individual proteins, these homology models provide the community with a starting point for structure-based design of drugs and vaccines as well as a for computational virtual screening

Case Report: Clotting Factor XII (Hageman) Deficiency Predisposing Acute non-hemorrhagic Stroke

Prolonged Activated Partial ThromboplastinTime (APTT) on routine coagulation screening would usually attract clinicianrsquos attention toward bleeding tendency specially when done as preoperative preparation. Factor XII (Hageman factor) is one of the factors involved in the intrinsic coagulation cascade and deficiency of these factors eventually prolong APTT with bleeding tendency. However, factor XII deficiency are more liable for thromboembolism through defective fibrinolytic pathway rather than bleeding tendency. A case of 27 years old male patient without past medical illnesses or significant risk factors presented with acute middle cerebral artery non-hemorrhagic stroke, screening to almost all etiological and predisposing factors were negative apart from prolonged APTT which was due to Factor XII (Hageman factor) deficiency

Development and characterization of new peptidomimetic inhibitors of the West Nile virus NS2B-NS3 protease

Potent inhibitors of the West Nile virus NS2B-NS3 protease could be useful drugs for the treatment of WNV infections. Therefore, in the present work, new substrate analogue inhibitors against the WNV protease have been developed. In this present work, new decarboxylated arginine memtics inhibitors against the WNV NS2B-NS3 protease were developed. In comparison to the known agmatine derivatives, the P1 trans-4-Guanidinocyclohexylmethylamid containing inhibitors have higher potency and selectivity against the WNV. Moreover, the first crystal structure of the WNV protease in complex with small noncovalently-binding inhibitor was solved