Biology subjects

Lopez, A. H.

Publications and source records attributed to Lopez, A. H..

3 recordsLinked to original sources

bioRxiv2025

Antimalarial Potential of Synthetic Geraniol and Nerol Analogs

Drug resistance is a major threat to malaria control, and thus new drugs are required to fight against this parasitosis. To accelerate drug development, it is of special interest the exploration of natural compounds or repositioning drugs already employed for other diseases. Considering this, previous studies have found that diverse plant terpenes arrest Plasmodium parasites in vitro and in vivo models. However, most terpenes possess low toxicity for the parasite and/or face pharmacokinetic issues. Here, we report several new acyclic monoterpene analogs which possess great antiplasmodial activity in vitro (50% inhibitory concentration at low micromolar scale) against P. falciparum parasites. Also, in vitro studies using hepatocellular carcinoma cells (HepG2) demonstrated remarkable selectivity for malaria parasites. Furthermore, bioinformatic approaches revealed that these compounds possess acceptable pharmacological properties. All these results suggest that acyclic monoterpene analogues could serve as a promising starting point for the development of synthetic terpenes as antimalarial drugs.

microbiology↗

bioRxiv2025

Interleukin-27 is antiviral at the maternal-fetal interface.

Congenital viral infections can have severe consequences for pregnancy and fetal outcomes. Remarkably, the fetal-derived placenta serves as a robust barrier to infection through meticulous regulation by immune effectors and a diverse repertoire of cytokines. Yet, the regulatory roles of many cytokines remain undefined at the maternal-fetal interface. Interleukin 27 (IL-27) is a highly expressed cytokine in the placenta whose functional consequence during congenital infection is unknown. Here, we utilized trophoblast organoids (TO) derived from primary human placentas and a mouse model of congenital viral infection to uncover the functional role of IL-27 signaling during pregnancy. We show that TOs constitutively express IL-27 and its receptor, IL27RA, and demonstrate that IL-27 signaling restricts Zika virus (ZIKV) infection of TOs. Through bulk RNA-sequencing of TOs in the absence and presence of IL-27 signaling, we demonstrate IL-27-mediated upregulation of antiviral genes. Finally, we show that IL-27 signaling is critical within the context of congenital murine ZIKV infection, as IL-27 restricts placental ZIKV burdens and protects against pathologic fetal outcomes early in gestation. These findings collectively demonstrate a novel role for IL-27 in the placenta and establish IL-27 as an innate antiviral defense at the maternal-fetal interface during congenital viral infection.

microbiology↗

bioRxiv2023

LY6E protects mice from pathogenic effects of murine coronavirus and SARS-CoV-2

LY6E is an antiviral protein that inhibits coronavirus entry. Its expression in immune cells allows mice to control murine coronavirus infection. However, it is not known which immune cell subsets mediate this control or whether LY6E protects mice from SARS-CoV-2. In this study, we used tissue-specific Cre recombinase expression to ablate Ly6e in distinct immune compartments or in all epiblast-derived cells, and bone marrow chimeras to target Ly6e in a subset of radioresistant cells. Mice lacking Ly6e in Lyz2-expressing cells and radioresistant Vav1-expressing cells were more susceptible to lethal murine coronavirus infection. Mice lacking Ly6e globally developed clinical disease when challenged with the Gamma (P.1) variant of SARS-CoV-2. By contrast, wildtype mice and mice lacking type I and type III interferon signaling had no clinical symptoms after SARS-CoV-2 infection. Transcriptomic profiling of lungs from SARS-CoV-2-infected wildtype and Ly6e knockout mice revealed a striking reduction of secretory cell-associated genes in infected knockout mice, including Muc5b, an airway mucin-encoding gene that may protect against SARS-CoV-2-inflicted respiratory disease. Collectively, our study reveals distinct cellular compartments in which Ly6e confers cell intrinsic antiviral effects, thereby conferring resistance to disease caused by murine coronavirus and SARS-CoV-2.

microbiology↗