Biology subjects

Sabariegos, R.

Publications and source records attributed to Sabariegos, R..

3 recordsLinked to original sources

bioRxiv2026

Phosphaphenalene Gold(I) Complexes as Broad-Spectrum Antivirals Against Emerging Flaviruses

Flaviviruses are emerging and re-emerging pathogens of major global health concern that can replicate in hosts of different phyla, including humans. Among them, Zika virus (ZIKV) is associated with severe neurological outcomes, including neonatal microcephaly, congenital malformations, and Guillain-Barre syndrome in adults. Usutu virus (USUV), another mosquito-borne flavivirus, primarily infects birds and has been linked to neurological symptoms in humans. Bagaza virus (BAGV) significantly affects the wildlife of some bird species and carries a noteworthy risk of zoonotic transmission. Despite their clinical significance, approved antiviral options for flaviviral infections (including ZIKV, USUV, and BAGV) are not available, and current management focuses primarily on providing symptomatic relief and supportive care. To address this therapeutic gap, we evaluated the antiviral activity of five phosphaphenalene-based gold (I) complexes. These phosphaphenalene-derived compounds exhibit straightforward and versatile chemistry, allowing access to derivatives with improved stability, bioactivity, selectivity, and cytotoxicity, thereby enhancing their biological activities. Two compounds showed potent inhibition of ZIKV, USUV, and BAGV replication at low micromolar concentrations, with ZIKV displaying greater sensitivity. ZIKV titers were reduced by up to three orders of magnitude in a dose-dependent fashion. Mechanistic studies revealed that both compounds inhibited thioredoxin reductase and disrupted autophagy. This study represents the first demonstration of the potential of phosphaphenalene-based gold (I) complexes as promising candidates against flavivirus infections, offering a promising foundation for the development of urgently needed antiviral therapies with potential impact on global health.

microbiology↗

bioRxiv2026

Isolation and characterization of Bagaza virus: insights into host adaptability and zoonotic potential.

Bagaza virus (BAGV) is an emerging orthoflavivirus that primarily infects wild birds, but its ability to infect other hosts remains poorly understood. We isolated BAGV RNA from the brain of a dead red-legged partridge and evaluated viral adaptation and replication kinetics in avian, mosquito, mammalian, and human cell lines. BAGV replicated efficiently in monkey, mosquito, duck, and selected human cell lines (HEK-293T and Huh7.5), whereas replication was limited in other human, hamster, and chicken fibroblast cell lines, indicating variable cellular susceptibility. These differences may reflect host-specific adaptation or distinct innate immune responses. Viral RNA replication complexes localized to the cytoplasm, as shown by immunocytochemical detection of dsRNA. Ribavirin treatment significantly reduced viral titers and RNA levels, demonstrating antiviral sensitivity. Together, these findings provide new insights into BAGV biology, host adaptability, and potential zoonotic risk, and support the development of antiviral strategies and improved epidemiological surveillance within a One Health framework.

microbiology↗

bioRxiv2020

Guanosine inhibits hepatitis C virus replication and increases indel frequencies, associated with altered intracellular nucleotide pools

In the course of experiments aimed at deciphering the inhibition mechanism of mycophenolic acid and ribavirin in hepatitis C virus (HCV) infection, we observed an inhibitory effect of the nucleoside guanosine (Gua). Here, we report that Gua and not the other standard nucleosides inhibits HCV replication in human hepatoma cells. Gua did not directly inhibit the in vitro polymerase activity of NS5B, but it modified the intracellular levels of nucleoside di- and tri-phosphate (NDPs and NTPs), leading to deficient HCV RNA replication and reduction of infectious progeny virus production. Changes in the concentrations of NTP or NDP modified NS5B RNA polymerase activity in vitro, in particular de novo RNA synthesis and template switching. Furthermore, the Gua-mediated changes were associated with a significant increase in the number of indels in viral RNA, which may account for the reduction of the specific infectivity of the viral progeny, suggesting the presence of defective genomes. Thus, a proper NTP:NDP balance appears to be critical to ensure HCV polymerase fidelity and minimal production of defective genomes. Author summaryRibonucleoside metabolism is essential for replication of RNA viruses. In this article we describe the antiviral activity of the natural ribonucleoside guanosine (Gua). We demonstrate that hepatitis C virus (HCV) replication is inhibited in the presence of increasing concentrations of this ribonucleoside and that this inhibition does not occur as a consequence of a direct inhibition of HCV polymerase. Cells exposed to increasing concentrations of Gua show imbalances in the intracellular concentrations of nucleoside-diphosphates and triphosphates and as the virus is passaged in these cells, it accumulates mutations that reduce its infectivity and decimate its normal spreading capacity.

microbiology↗