Biology subjects

Nieto, N.

Publications and source records attributed to Nieto, N..

3 recordsLinked to original sources

bioRxiv2022

Promising Antimalarials targeting Apicoplast DNA Polymerase from Plasmodium falciparum

Malaria is caused by the parasite Plasmodium falciparum, which contains an essential non-photosynthetic plastid called the apicoplast. A single DNA polymerase, apPOL, is targeted to the apicoplast, where it replicates and repairs the genome. apPOL has no direct orthologs in mammals and is considered a promising drug target for the treatment and/or prevention of malaria. We previously reported screening the Malaria Box to identify MMV666123 as an inhibitor of apPOL. Herein we extend our studies and report structure-activity relationships for MMV666123 and identify key structural motifs necessary for inhibition. Although attempts to crystallize apPOL with the inhibitor were not fruitful, kinetic analysis and crystal structure determinations of WT and mutant apo-enzymes, facilitated model building and provided insights into the putative inhibitor binding site. Our results validate apPOL as an antimalarial target and provide an avenue for the design of high potency, specific inhibitors of apPOL and other A-family DNA polymerases.

biochemistry↗

bioRxiv2022

Discovery of small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase

Malaria is caused by infection with protozoan parasites of the Plasmodium genus, which is part of the phylum Apicomplexa. Most organisms in this phylum contain a relic plastid called the apicoplast. The apicoplast genome is replicated by a single DNA polymerase (apPOL), which is an attractive target for anti-malarial drugs. We screened small-molecule libraries (206,504 compounds) using a fluorescence-based high-throughput DNA polymerase assay. Dose/response analysis and counter-screening identified 186 specific apPOL inhibitors. Toxicity screening against human HepaRG human cells removed 84 compounds and the remaining were subjected to parasite killing assays using chloroquine resistant P. falciparum parasites. Nine compounds were potent inhibitors of parasite growth and may serve as lead compounds in efforts to discover novel malaria drugs.

biochemistry↗

bioRxiv2021

"Thinking out loud": an open-access EEG-based BCI dataset for inner speech recognition

Surface electroencephalography is a standard and noninvasive way to measure electrical brain activity. Recent advances in artificial intelligence led to significant improvements in the automatic detection of brain patterns, allowing increasingly faster, more reliable and accessible Brain-Computer Interfaces. Different paradigms have been used to enable the human-machine interaction and the last few years have broad a mark increase in the interest for interpreting and characterizing the "inner voice" phenomenon. This paradigm, called inner speech, raises the possibility of executing an order just by thinking about it, allowing a "natural" way of controlling external devices. Unfortunately, the lack of publicly available electroencephalography datasets, restricts the development of new techniques for inner speech recognition. A ten-subjects dataset acquired under this and two others related paradigms, obtained with an acquisition system of 136 channels, is presented. The main purpose of this work is to provide the scientific community with an open-access multiclass electroencephalography database of inner speech commands that could be used for better understanding of the related brain mechanisms.

neuroscience↗