Biology subjects

Torres, P. H. M.

Publications and source records attributed to Torres, P. H. M..

4 recordsLinked to original sources

bioRxiv2025

Mutational spectra reveal influenza virus transmission routes and adaptation

Influenza A virus remains a major cause of morbidity and mortality in humans and animals with pandemic potential. While control of outbreaks and spillover events remains a key health priority, the transmission routes and adaptations causing these episodes remain unclear. To understand these processes, we compared mutational spectra across the complete diversity of influenza A virus. We find that niche-specific mutagens cause large convergent shifts in mutational spectrum between gastrointestinal and respiratory lineages, allowing inference of transmission route and site of infection, while additional mutational patterns are host-specific, permitting detection of species responsible for outbreaks. By identifying points of spectrum change in phylogenetic trees, we discover novel adaptive mutations enabling sustained respiratory transmission. We conclude that mutational spectra can enable early detection of lineages with increased potential for spillover and onward transmission, and should be considered as a component of genomic surveillance strategies.

microbiology↗

bioRxiv2021

Predicted structural mimicry of spike receptor-binding motifs from highly pathogenic human coronaviruses

Viruses often encode proteins that mimic host proteins in order to facilitate infection. Little work has been done to understand the potential mimicry of the SARS-CoV-2, SARS-CoV, and MERS-CoV spike proteins, particularly the receptor-binding motifs, which could be important in determining tropism of the virus. Here, we use structural bioinformatics software to characterize potential mimicry of the three coronavirus spike protein receptor-binding motifs. We utilize sequence-independent alignment tools to compare structurally known or predicted three-dimensional protein models with the receptor-binding motifs and verify potential mimicry with protein docking simulations. Both human and non-human proteins were found to be similar to all three receptor-binding motifs. Similarity to human proteins may reveal which pathways the spike protein is co-opting, while analogous non-human proteins may indicate shared host interaction partners and overlapping antibody cross-reactivity. These findings can help guide experimental efforts to further understand potential interactions between human and coronavirus proteins. HighlightsO_LIPotential coronavirus spike protein mimicry revealed by structural comparison C_LIO_LIHuman and non-human protein potential interactions with virus identified C_LIO_LIPredicted structural mimicry corroborated by protein-protein docking C_LIO_LIEpitope-based alignments may help guide vaccine efforts C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/441187v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1f09454org.highwire.dtl.DTLVardef@19a5557org.highwire.dtl.DTLVardef@158d3fdorg.highwire.dtl.DTLVardef@c59511_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2019

Inhibiting Mycobacterium tuberculosis CoaBC by targeting a new allosteric site.

Coenzyme A (CoA) is a fundamental co-factor for all life, involved in numerous metabolic pathways and cellular processes, and its biosynthetic pathway has raised substantial interest as a drug target against multiple pathogens including Mycobacterium tuberculosis. The biosynthesis of CoA is performed in five steps, with the second and third steps being catalysed in the vast majority of prokaryotes, including M. tuberculosis, by a single bifunctional protein, CoaBC. Depletion of CoaBC was found to be bactericidal in M. tuberculosis. Here we report the first structure of a full-length CoaBC, from the model organism Mycobacterium smegmatis, describe how it is organised as a dodecamer and regulated by CoA thioesters. A high-throughput biochemical screen focusing on CoaB identified two inhibitors with different chemical scaffolds. Hit expansion led to the discovery of potent inhibitors of M. tuberculosis CoaB, which we show to bind to a novel cryptic allosteric site within CoaB.

biochemistry↗

bioRxiv2017

Genomic and structural features of the Yellow Fever virus from the 2016-2017 Brazilian outbreak

Brazil has been suffering a severe sylvatic epidemic of yellow fever virus (YFV) since late 2016. Analysis of full-length YFV genomes from all hosts involved in the Brazilian 2017 outbreak reveals that they belong to sub-lineage 1E within modern-lineage, but display several unique amino acid substitutions in highly conserved positions at NS3 and NS5 viral proteins. Evolutionary analyses indicate that YFV carrying that set of amino acid substitution circulates in the Southern Brazilian region for several months before being detected in December 2016. Structural and selection analyses support that some of these substitutions were under positive selection and could impact enzyme structure and function. Altogether, this evidence demonstrated that the current Brazilian YFV carries unique amino acid signatures in the non-structural proteins and support the hypothesis that those substitutions may be affecting the viral fitness and transmissibility.

microbiology↗