Biology subjects

Andreu-Moreno, I.

Publications and source records attributed to Andreu-Moreno, I..

4 recordsLinked to original sources

bioRxiv2026

Anticipatory discovery of entry inhibitors against emerging viruses guided by viral phylogeny

Emerging viruses pose a major threat to global health, underscoring the need to improve antiviral preparedness. Here, we developed a phylogenetically-informed framework to identify entry inhibitors with potential activity against yet-to-emerge viruses. First, using pseudotypes displaying the receptor-binding proteins (RBPs) of 8 enveloped RNA viruses from different families, we screened a library of 2,320 FDA-approved compounds to identify candidate entry inhibitors. Hits were tested for potency, selectivity, consistency across cell types and pseudotyping vectors and, in some cases, were validated using authentic viruses. Then, to define the breadth of antiviral activity, 25 selected drugs were assayed against an expanded panel of 68 RBPs from 13 families, as well as against pairs of closely related RBPs. This revealed both narrow and broad-range inhibitors, including selective estrogen receptor modulators, alkaloids, aminoquinolines, and anidulafungin, which showed particularly broad activity. Importantly, RBPs from the same phylogenetic cluster frequently displayed correlated drug-sensitivity profiles, indicating that antiviral effects are predictable across closely related viruses. Our findings provide a proof of concept for anticipatory antiviral discovery, showing that phylogenetic relationships can guide the identification of entry inhibitors against potential future zoonotic threats.

microbiology↗

bioRxiv2024

Genetic diversity and cross-species transmissibility of bat-associated picornaviruses from Spain

BackgroundEmerging zoonotic diseases arise from cross-species transmission events between wild or domesticated animals and humans, with bats being one of the major reservoirs of zoonotic viruses. Viral metagenomics has led to the discovery of many viruses, but efforts have mainly been focused on some areas of the world and on certain viral families. MethodsWe set out to describe full-length genomes of new picorna-like viruses by collecting feces from hundreds of bats captured in different regions of Spain. Viral sequences were obtained by high-throughput Illumina sequencing and analyzed phylogenetically to classify them in the context of known viruses. Linear discriminant analysis (LDA) was performed to infer likely hosts based on genome composition. ResultsWe found five complete or nearly complete genomes belonging to the family Picornaviridae, including a new species of the subfamily Ensavirinae. LDA suggested that these were true vertebrate viruses, rather than viruses from the bat diet. Some of these viruses were related to picornaviruses previously found in other bat species from distant geographical regions. We also found a calhevirus genome that most likely belongs to a proposed new family within the order Picornavirales, and for which genome composition analysis suggested a plant host. ConclusionsOur findings describe new picorna-like viral species and variants circulating in the Iberian Peninsula, illustrate the wide geographical distribution and interspecies transmissibility of picornaviruses, and suggest new hosts for calheviruses.

microbiology↗

bioRxiv2024

Viral entry is a weak barrier to zoonosis

Recent advances in viral metagenomics have led to the discovery of many mammalian viruses, but experimental tests to determine whether they pose a threat to humans are largely lacking. A first step for a virus to cross the species barrier is to penetrate host cells. Here, we use gene synthesis and viral pseudotyping to experimentally test the ability of viral receptor-binding proteins (RBPs) from >100 enveloped RNA viruses to mediate entry into human cells. Analysis of thousands of RBP-cell pairs demonstrated such ability for most viruses, with significant variation among the 14 viral families studied. Comparison of RBP-mediated infectivity with cellular gene expression data showed that viral entry is often not limited by the presence of a receptor and revealed the contribution of additional host factors. Our results prove the weakness of interspecies barriers at the early stages of infection and identify molecular interactions that enable viral zoonosis.

microbiology↗

bioRxiv2023

An efficient plasmid-based system for the recovery of recombinant vesicular stomatitis virus encoding foreign glycoproteins

Viral glycoproteins mediate entry into host cells, thereby dictating host range and pathogenesis. In addition, they constitute the principal target of neutralizing antibody responses, making them important antigens in vaccine development. Recombinant vesicular stomatitis virus (VSV) encoding foreign glycoproteins can provide a convenient and safe surrogate system to interrogate the function, evolution, and antigenicity of viral glycoproteins from viruses that are difficult to manipulate or those requiring high biosafety levels containment. However, the production of recombinant VSV can be technically challenging. In this work, we present an efficient and robust plasmid-based system for the production of recombinant VSV encoding foreign glycoproteins. We validate the system using glycoproteins from different viral families, including arenaviruses, coronaviruses, and hantaviruses, as well as highlight their utility for studying the effects of mutations on viral fitness. Overall, the methods described herein can facilitate the study of both native and recombinant VSV encoding foreign glycoproteins and can serve as the basis for the production of VSV-based vaccines.

microbiology↗