Biology subjects

Belmonte Reche, E.

Publications and source records attributed to Belmonte Reche, E..

2 recordsLinked to original sources

bioRxiv2020

Exploring G and C-quadruplex structures as potential targets against the severe acute respiratory syndrome coronavirus 2

In this paper we report the analysis of the 2019-nCoV genome and related viruses using an upgraded version of the open-source algorithm G4-iM Grinder. This version improves the functionality of the software, including an easy way to determine the potential biological features affected by the candidates found. The quadruplex definitions of the algorithm were optimized for 2019-nCoV. Using a lax quadruplex definition ruleset, which accepts amongst other parameters two residue G- and C-tracks, hundreds of potential quadruplex candidates were discovered. These sequences were evaluated by their in vitro formation probability, their position in the viral RNA, their uniqueness and their conservation rates (calculated in over three thousand different COVID-19 clinical cases and sequenced at different times and locations during the ongoing pandemic). These results were compared sequentially to other Coronaviridae members, other Group IV (+)ssRNA viruses and the entire realm. Sequences found in common with other species were further analyzed and characterized. Sequences with high scores unique to the 2019-nCoV were studied to investigate the variations amongst similar species. Quadruplex formation of the best candidates was then confirmed experimentally. Using NMR and CD spectroscopy, we found several highly stable RNA quadruplexes that may be suitable theranostic targets against the 2019-nCoV. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/257493v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@1ab4843org.highwire.dtl.DTLVardef@152ebeorg.highwire.dtl.DTLVardef@afd7aforg.highwire.dtl.DTLVardef@793707_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2019

G4-iM Grinder: DNA and RNA G-Quadruplex, i-Motif and higher order structure search and analyser tool

Herein, we present G4-iM Grinder as a system for potential G4, i-Motif and higher-order structure identification and characterization. Several grading tools of biological relevance and G4 in vitro formation probability are included in this highly modulable and robust engine. G4-iM Grinder improves other current quadruplex search engines when compared in capabilities and processing time. We used G4-iM Grinder in the analysis of the complete human genome whilst focusing on frequency and score of G-based structures. We studied the most recurrent potential quadruplex sequences (PQS) and the longest highest scoring potential higher order quadruplex sequences (PHOQS) in our genome. As proof of the analytical capabilities of G4-iM Grinder, we also analysed a new PHOQS and predicted the most probable PQS subunits to form it. Taking the human average PQS density as reference, we examined the genomes of organisms that cause leishmaniosis, diphtheria, brucellosis, meningitis, pneumonia, toxoplasmosis, tuberculosis, leprosy, AIDS, dengue fever and hepatitis C, and found they are very rich in PQS. G4-iM Grinder identified within many of these organisms several already known-to-form G4 sequences. Together, this suggests that G4-quadruplexes may potentially be important therapeutic targets against many of these organisms that currently kill millions worldwide. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/532382v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@b01c08org.highwire.dtl.DTLVardef@56b3org.highwire.dtl.DTLVardef@3c1a63org.highwire.dtl.DTLVardef@1e88e04_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗