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Biology subjects

Kopec, A.

Publications and source records attributed to Kopec, A..

2 recordsLinked to original sources
bioRxiv2026

Antiviral drug synergy and mutational signatures in different epithelial cell models of RSV and hPIV infection

Despite the huge global health burden presented by respiratory viruses, effective broad-spectrum antiviral therapeutic options remain limited. Here we evaluated the antiviral activity of four RNA-dependent RNA polymerase (RdRp) inhibitors, remdesivir, ribavirin, favipiravir, and molnupiravir, against respiratory syncytial virus (RSV) and human parainfluenza (hPIV) using monotherapy or dual-drug combinations with epithelial cell lines and primary human airway culture models. Remdesivir showed the greatest potency across both viruses, while ribavirin and favipiravir also demonstrated inhibition. Molnupiravir was active against RSVA but not hPIV3. Several dual-drug combinations, including remdesivir-favipiravir, remdesivir-molnupiravir and favipiravir-molnupiravir, produced marked synergy against RSVA, and more limited synergy for hPIV3. Antiviral efficacy was validated in primary airway epithelial cultures, where effective concentrations preserved epithelial integrity and attenuated viral disruption of ciliary function. Across both viruses, increasing antiviral exposure was associated with dose-dependent signature mutagenesis. Importantly, antivirals induced significantly higher RSVA mutation burden in the primary airway model. These findings highlight the therapeutic potential of RdRp inhibitor combinations for RSVA and hPIV3, provide mechanistic insight through antiviral-related mutational signatures and demonstrate advantages of the primary human airway culture model for development of effective multi-drug regimens and broad-spectrum antiviral preparedness. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/699296v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1eb00dforg.highwire.dtl.DTLVardef@186358forg.highwire.dtl.DTLVardef@265181org.highwire.dtl.DTLVardef@1b10d0e_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗
bioRxiv2017

Microglial elimination of dopamine D1 receptors defines sex-specific changes in nucleus accumbens development and social play behavior during adolescence

Adolescence is a developmental period in which the mesolimbic dopaminergic reward circuitry of the brain, including the nucleus accumbens (NAc), undergoes significant developmental plasticity and neural circuit maturation. Dopamine D1 receptors (D1rs) in the NAc have recently been demonstrated to be critical modulators of social behavior, but how these receptors are regulated in adolescence to mediate social behavior is not well understood. In this report, we used multi-plexed immunohistochemistry with volumetric reconstructions, co-immunoprecipitation, ex vivo, and in vivo stereotaxic, microglial manipulation, and social behavior assessment to demonstrate that microglia and complement-mediated phagocytic activity shapes sex-specific NAc development. Moreover, we report for the first time that microglia-mediated phagocytosis is required for natural developmental changes in behavior, specifically, adolescent male social play behavior. These data have broad implications for understanding how experience interacts with the developing reward circuity, sex-specific responses to stimuli in adolescence, and how neuropsychiatric disorders may arise in a sexually dimorphic manner.

neuroscience↗