Identification of proteins and cellular pathways targeted by 2-nitroimidazole hypoxic cytotoxins by Faisal Bin Rashed, Alexandru Cezar Stoica, Dawn MacDonald, Hassan El-Saidi, Carolynne Ricardo, Bhumi Bhatt, Jack Moore, Diana Diaz-Dussan, Nirilanto Ramamonjisoa, Yvonne Mowery, Sambasivarao Damaraju, Richard Fahlman, Piyush Kumar, Michael Weinfeld

“…Critical cellular proteins such as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the detoxification enzyme glutathione S-transferase P (GSTP1) appeared as top hits, and N3-AZA adduct formation significantly reduced their enzymatic activities only under hypoxia. …”
Get full text

PRMT5 inhibition shows in vitro efficacy against H3K27M-altered diffuse midline glioma, but does not extend survival in vivo by Elizabeth J. Brown, Leire Balaguer-Lluna, Adam P. Cribbs, Martin Philpott, Leticia Campo, Molly Browne, Jong Fu Wong, Udo Oppermann, Ángel M. Carcaboso, Alex N. Bullock, Gillian Farnie

“…Here, we performed wider screening of an epigenetic inhibitor library and identified inhibitors of protein arginine methyltransferases (PRMTs) among the top hits reducing DMG cell viability. Two of the most effective inhibitors, LLY-283 and GSK591, were targeted against PRMT5 using distinct binding mechanisms and reduced the viability of a subset of DMG cells expressing wild-type TP53 and mutant ACVR1. …”
Get full text

RECENT COLLECTION OF THE POISONOUS MUSHROOM, Clarkeinda trachodes (Berk.) FOR INDONESIA by Ivan Permana Putra, Oktan Dwi Nurhayat, Wahyu AJi Mahardika, Okta Yulia Sari

“…The BLAST result showed that our specimen has a high similarity to C. trachodes as the top hits. In addition, the phylogenetic tree constructed by ITS sequence committed specimen BO24637 as C. trachodes with 100% BS value. …”
Get full text

Virtual screening using covalent docking to find activators for G245S mutant p53. by Sara Ibrahim Omar, Marco Gaetano Lepre, Umberto Morbiducci, Marco Agostino Deriu, Jack A Tuszynski

“…Based on its binding scores and ADMET risk score, compound 2 is likely to have the best potential as a G245S-mp53 activator compared to the other top hits.…”
Get full text

Genetically regulated gene expression underlies lipid traits in Hispanic cohorts. by Angela Andaleon, Lauren S Mogil, Heather E Wheeler

“…We performed genome-wide (GWAS) and imputed transcriptome-wide association studies of four lipid traits in the Hispanic Community Health Study/Study of Latinos cohort (HCHS/SoL, n = 11,103), replicated top hits in the Multi-Ethnic Study of Atherosclerosis (MESA, n = 3,855), and compared the results to the larger, predominantly European ancestry meta-analysis by the Global Lipids Genetics Consortium (GLGC, n = 196,475). …”
Get full text

TRIM25 Enhances the Antiviral Action of Zinc-Finger Antiviral Protein (ZAP). by Melody M H Li, Zerlina Lau, Pamela Cheung, Eduardo G Aguilar, William M Schneider, Leonia Bozzacco, Henrik Molina, Eugen Buehler, Akinori Takaoka, Charles M Rice, Dan P Felsenfeld, Margaret R MacDonald

“…In order to exclude off-target effects, we carry out stringent confirmatory assays to verify the top hits. Important ZAP-liaising partners identified include proteins involved in membrane ion permeability, type I IFN signaling, and post-translational protein modification. …”
Get full text

A comprehensive strategy to discover inhibitors of the translesion synthesis DNA polymerase κ. by Kinrin Yamanaka, Dorjbal Dorjsuren, Robert L Eoff, Martin Egli, David J Maloney, Ajit Jadhav, Anton Simeonov, R Stephen Lloyd

“…A high-throughput, fluorescence-based DNA strand displacement assay was utilized to screen ∼16,000 bioactive compounds, and the 60 top hits were validated by primer extension assays using non-damaged DNAs. …”
Get full text

Identification of β2 microglobulin, the product of B2M gene, as a Host Factor for Vaccinia Virus Infection by Genome-Wide CRISPR genetic screens. by Alejandro Matía, Maria M Lorenzo, Yolimar C Romero-Estremera, Juana M Sánchez-Puig, Angel Zaballos, Rafael Blasco

“…Additionally, we consistently found β2-microglobulin, encoded by the B2M gene, among the screening top hits, a novel finding that was further explored. …”
Get full text

Kinome-wide RNAi screen implicates at least 5 host hepatocyte kinases in Plasmodium sporozoite infection. by Miguel Prudêncio, Cristina D Rodrigues, Michael Hannus, Cécilie Martin, Eliana Real, Lígia A Gonçalves, Céline Carret, Robert Dorkin, Ingo Röhl, Kerstin Jahn-Hoffmann, Adrian J F Luty, Robert Sauerwein, Christophe J Echeverri, Maria M Mota

“…Five protein kinases thereby emerged as top hits, all of which caused significant reductions in infection when silenced by RNAi. …”
Get full text

Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22. by Evangelou, E, Valdes, A, Kerkhof, H, Styrkarsdottir, U, Zhu, Y, Meulenbelt, I, Lories, R, Karassa, F, Tylzanowski, P, Bos, S, Akune, T, Arden, N, Carr, A, Chapman, K, Cupples, L, Dai, J, Deloukas, P, Doherty, M, Doherty, S, Engstrom, G, Gonzalez, A, Halldorsson, B, Hammond, C, Hart, D, Helgadottir, H

“…METHODS: A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. …”

Selecting antibacterial aptamers against the BamA protein in Pseudomonas aeruginosa by incorporating genetic algorithm to optimise computational screening method by Rupany Selvam, Ian Han Yan Lim, Jovita Catherine Lewis, Chern Hong Lim, Michelle Khai Khun Yap, Hock Siew Tan

“…Additionally, genetic algorithm analysis was carried out to rank the aptamers based on their binding affinity. The top hits of aptamers with good binding to BamA protein were synthesised to investigate their in vitro antibacterial activity. …”
Get full text

De Novo assembly of the Japanese flounder (Paralichthys olivaceus) spleen transcriptome to identify putative genes involved in immunity. by Lin Huang, Guiyang Li, Zhaolan Mo, Peng Xiao, Jie Li, Jie Huang

“…A total of 21,391 unigenes (22.14%) were annotated in the NCBI Nr database, and only 1.1% of the BLASTx top-hits matched P. olivaceus protein sequences. Approximately 12,503 (58.45%) unigenes were categorized into three Gene Ontology groups, 19,547 (91.38%) were classified into 26 Cluster of Orthologous Groups, and 10,649 (49.78%) were assigned to six Kyoto Encyclopedia of Genes and Genomes pathways. …”
Get full text

Analysis of Paired Primary-Metastatic Hormone-Receptor Positive Breast Tumors (HRPBC) Uncovers Potential Novel Drivers of Hormonal Resistance. by Luis Manso, Silvana Mourón, Michael Tress, Gonzalo Gómez-López, Manuel Morente, Eva Ciruelos, Miriam Rubio-Camarillo, Jose Luis Rodriguez-Peralto, Miguel A Pujana, David G Pisano, Miguel Quintela-Fandino

“…Comparative genomic hybridization was performed as well. Top hits, based on the frequency of alteration and severity of the changes, were tested in the TCGA series. …”
Get full text

Herpesvirus deconjugases inhibit the IFN response by promoting TRIM25 autoubiquitination and functional inactivation of the RIG-I signalosome. by Soham Gupta, Päivi Ylä-Anttila, Simone Callegari, Ming-Han Tsai, Henri-Jacques Delecluse, Maria G Masucci

“…Several members of the 14-3-3-family of scaffold proteins were found amongst the top hits of the BPLF1 interactome, suggesting that, through this interaction, BPLF1 may regulate a variety of cellular signaling pathways. …”
Get full text

Genome-wide CRISPR screen identifies genes synthetically lethal with GRA17, a nutrient channel encoding gene in Toxoplasma. by Tatiana C Paredes-Santos, Mebratu A Bitew, Christopher Swale, Felipe Rodriguez, Shruthi Krishnamurthy, Yifan Wang, Parag Maru, Lamba Omar Sangaré, Jeroen P J Saeij

“…Several of these genes were involved in the correct localization of GRAs, including GRA17/GRA23, to the PVM. One of the top hits, GRA72, was predicted to form a pore on the PVM, and its deletion led to the formation of enlarged "bubble vacuoles" with reduced PVM small molecule permeability, similar to what was previously observed for Δgra17 parasites. …”
Get full text

Discovery of novel natural products for mosquito control by Cecilia S. Engdahl, Chinmay V. Tikhe, George Dimopoulos

“…We show that a selection of the natural product top hits, bactobolin, maytansine and ossamycin, also killed the larval stages of the malaria-transmitting mosquito Anopheles gambiae as well as the adult form of both species. …”
Get full text

Lead generation of UPPS inhibitors targeting MRSA: Using 3D-QSAR pharmacophore modeling, virtual screening, molecular docking, and molecular dynamic simulations by Basma M. Qandeel, Samar Mowafy, Khaled Abouzid, Nahla A. Farag

“…Moreover, molecular dynamic simulations of the top hits were performed to confirm the stability of the protein–ligand complexes, yielding five promising novel UPPS inhibitors. …”
Get full text

A score of the ability of a three-dimensional protein model to retrieve its own sequence as a quantitative measure of its quality and appropriateness. by León P Martínez-Castilla, Rogelio Rodríguez-Sotres

“…CONCLUSION: Because the sequence of the native protein used to create the Rd.HMM model was always amongst the top hits, the procedure is a reliable tool to score, very accurately, the quality and appropriateness of computer-modeled 3D-structures, without the need for spectroscopy data. …”
Get full text

Remdesivir and Ledipasvir among the FDA-Approved Antiviral Drugs Have Potential to Inhibit SARS-CoV-2 Replication by Rameez Hassan Pirzada, Muhammad Haseeb, Maria Batool, MoonSuk Kim, Sangdun Choi

“…The methodology adopted was virtual screening and docking of FDA-approved antiviral drugs into the RdRp protein. Top hits were selected and subjected to molecular dynamics simulations to understand the dynamics of RdRp in complex with these drugs. …”
Get full text

Drug-induced diabetes type 2: In silico study involving class B GPCRs. by Dorota Latek, Ewelina Rutkowska, Szymon Niewieczerzal, Judyta Cielecka-Piontek

“…In addition, we also described several top hits as potential substitutes of peptidic incretin mimetics which were discovered in the drug repositioning screen using gut hormone receptors structures against the ZINC15 compounds subset.…”
Get full text