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Cryptosporidium parvum is a highly prevalent zoonotic and anthroponotic protozoan parasite that causes a diarrheal syndrome in children and neonatal livestock, culminating in growth retardation and mortalities. Despite the high prevalence of C. parvum, there are no fully effective and safe drugs for treating infections, and there is no vaccine. We have previously reported that the bacterial-like C. parvum lactate dehydrogenase (CpLDH) enzyme is essential for survival, virulence and growth of C. parvum in vitro and in vivo. In the present study, we screened compound libraries and identified inhibitors against the enzymatic activity of recombinant CpLDH protein in vitro. We tested the inhibitors for anti-Cryptosporidium effect using in vitro infection assays of HCT-8 cells monolayers and identified compounds NSC158011 and NSC10447 that inhibited the proliferation of intracellular C. parvum in vitro, with IC50 values of 14.88 and 72.65 μM, respectively. At doses tolerable in mice, we found that both NSC158011 and NSC10447 consistently significantly reduced the shedding of C. parvum oocysts in infected immunocompromised mice's feces, and prevented intestinal villous atrophy as well as mucosal erosion due to C. parvum. Together, our findings have unveiled promising anti-Cryptosporidium drug candidates that can be explored further for the development of the much needed novel therapeutic agents against C. parvum infections.
Pubmed ID: 31356619
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A molecular visualization program for displaying, animating, and analyzing large biomolecular systems using 3-D graphics and built-in scripting. VMD supports computers running MacOS X, Unix, or Windows, is distributed free of charge, and includes source code.
View all literature mentionsNIH genetic sequence database that provides annotated collection of all publicly available DNA sequences for almost 280 000 formally described species (Jan 2014) .These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. It is part of International Nucleotide Sequence Database Collaboration and daily data exchange with European Nucleotide Archive (ENA) and DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through NCBI Entrez retrieval system, which integrates data from major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of GenBank database are available by FTP.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsCollection of information about chemical structures and biological properties of small molecules and siRNA reagents hosted by the National Center for Biotechnology Information (NCBI).
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE, documented on February 1st, 2022. Software application for genetic analysis of classical biometric traits like blood pressure or height that are caused by a combination of polygenic inheritance and complex environmental forces. (entry from Genetic Analysis Software)
View all literature mentionsFoundation to help all people lead healthy, productive lives, this funding and job resource is focused on health, poverty, and opportunity. They work with partner organizations worldwide to tackle critical problems in four program areas. Their Global Development Division works to help the world''s poorest people lift themselves out of hunger and poverty. Their Global Health Division aims to harness advances in science and technology to save lives in developing countries. Their United States Division works to improve U.S. high school and postsecondary education and support vulnerable children and families in Washington State. And their Global Policy & Advocacy Division seeks to build strategic relationships and promote policies that will help advance their work. Our approach to grantmaking in all four areas emphasizes collaboration, innovation, risk-taking, and, most importantly, results. The foundation is unable to make grants directly to individuals. The majority of our funding is proactive and made to U.S. tax-exempt organizations that are independently identified by our staff.
View all literature mentionsPublic research university in Illinois and flagship institution of University of Illinois System. Founded in 1867 its campus is located in twin cities of Champaign and Urbana.
View all literature mentionsSoftware graphical user interface to help to set up which bonds will treated as rotatable in the ligand and to analyze dockings. Used for automated docking with selective receptor flexibility. Designed to predict how small molecules, such as substrates or drug candidates, bind to receptor of known 3D structure.
View all literature mentionsFirst of all, and most importantly, PC and Mac versions have been resynchronized. Support for direct login modelling submissions and result retrieval to/from the SwissModel Workspace Enhanced Import Menu Enhanced user interface with taxonomy support, and new sequence alignment features. New 3D Motif Searching feature Easy access to external user defined scripts directly from the interface Revised Help files accessible from the interface Swiss-PdbViewer (aka DeepView) is an application that provides a user friendly interface allowing to analyze several proteins at the same time. The proteins can be superimposed in order to deduce structural alignments and compare their active sites or any other relevant parts. Amino acid mutations, H-bonds, angles and distances between atoms are easy to obtain thanks to the intuitive graphic and menu interface. Swiss-PdbViewer can also read electron density maps, and provides various tools to build into the density. In addition, various modeling tools are integrated and command files for popular energy minimization packages can be generated. Finally, as a special bonus, POV-Ray scenes can be generated from the current view in order to make stunning ray-traced quality images.
View all literature mentionsCell line HCT 8 is a Cancer cell line with a species of origin Homo sapiens (Human)
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