Biology subjects

Kratka, Z.

Publications and source records attributed to Kratka, Z..

3 recordsLinked to original sources

bioRxiv2026

Human antibodies against West Nile and related orthoflaviviruses

West Nile virus (WNV) is a mosquito-borne pathogen of global concern that can cause fatal neuroinvasive disease. No specific prophylaxis or treatment exists for WNV or related orthoflavivirus infections, and the determinants of human disease severity remain poorly understood. Here, we report that neutralizing autoantibodies against type I interferons do not impair antiviral antibody development. Among the fully human monoclonal antibodies with potent neutralizing activity against WNV that were discovered, W010 targets a unique epitope within the envelope protein domain III (EDIII) and confers both pre- and post-exposure protection in a murine WNV model, even when interferon signaling is impaired. A second protective antibody, W014, exhibits broad cross-neutralization of other pathogenic orthoflavivirus members, including Japanese encephalitis virus, Murray Valley encephalitis virus, Saint Louis encephalitis virus, and Usutu virus. These findings identify key neutralizing epitopes on WNV EDIII and provide candidates for the development of antibody-based interventions against encephalitic orthoflavivirus infections.

immunology↗

bioRxiv2025

Bemnifosbuvir and remdesivir inhibit tick-borne encephalitis virus infection in complementary in vitro and ex vivo disease models

The geographical distribution and incidence of tick-borne encephalitis (TBE) have steeply increased over the past decades, raising to represent a major health concern in Asia and Europe. Symptoms of TBE, caused by infections with tick-borne encephalitis virus (TBEV), range from mild, flu-like symptoms to severe neurological disease, often accompanied by long-term sequelae persisting for several years following pathogen encounter. While effective vaccines against TBEV are available, no antiviral drugs are currently approved and therapeutic options for patients suffering from TBE are limited to supportive measures. Compounds able to disrupt viral nucleic acid synthesis bear the potential of effectively limiting viral replication and spread. Seeking to fill the therapeutic gap, we evaluated the efficacy of a panel of approved and investigational antiviral compounds in containing TBEV infection. Combining several cell lines, human neural organoids and organotypic rat brain slice cultures, we found that the nucleoside analogs remdesivir and bemnifosbuvir efficiently limit viral replication. Through infectious virus quantification, immunofluorescence analysis and flow cytometry, we report significant, dose-dependent reduction of viral loads across all models used, with inhibition observed at low doses for both drugs. Notably, while we observed bemnifosbuvir to be well tolerated, we report important cytotoxicity of remdesivir when applied to human neural organoids. Our findings identify bemnifosbuvir and remdesivir as novel treatment strategies for TBE, providing an accessible and timely response to a clinical challenge of pressing concern.

microbiology↗

bioRxiv2024

Bioenergetics of human spermatozoa in patients with testicular germ cell tumour

In testicular germ cell tumour (TGCT) patients, sperm cryopreservation prior to anti-cancer treatment represents the main fertility preservation approach. However, it is associated with low sperm recovery rate after thawing. Since sperm is a high-energy demanding cell, which is supplied by glycolysis and oxidative phosphorylation (OXPHOS), mitochondrial dysfunctionality can directly result in sperm anomalies. In this study, we investigated the bioenergetic pattern of cryopreserved sperm of TGCT patients in comparison with normozoospermic samples using two state-of-the-art methods; the Extracellular Flux Analyzer (XF Analyzer) and Two-Photon Fluorescence Lifetime imaging (2P-FLIM), in order to assess the contributions of OXPHOS and glycolysis to energy provision. A novel protocol for combined measurement of OXPHOS (Oxygen Consumption Rate - OCR) and glycolysis (Extracellular Acidification Rate - ECAR) using the XF Analyzer was developed together with a unique customized AI-based approach for semiautomated processing of 2P-FLIM images. Our study delivers optimized Low-HEPES modified Human Tubal Fluid media (mHTF) for sperm handling during pre-analytical and analytical phases to maintain sperm physiological parameters and optimal OCR, equivalent of OXPHOS. The negative effect of cryopreservation was signified by deterioration of both bioenergetic pathways represented by modified OCR and ECAR curves and the derived parameters. This was true for normozoospermic as well as TGCT samples, which showed even a stronger damage within the respiratory chain compared to the level of glycolytic activity impairment. The impact of cryopreservation and pathology are supported by 2P-FLIM analysis showing a significant decrease in bound NADH in contrast to unbound NAD(P)H which reflects decreased metabolic activity in samples from TGCT patients. Our study provides novel insight into the impact of TGCT on sperm bioenergetics and delivers a verified protocol to be used for assessment of human sperm metabolic activity, which can be a valuable tool for further research and clinical andrology. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/595824v2_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@130b9eeorg.highwire.dtl.DTLVardef@1fec841org.highwire.dtl.DTLVardef@d401forg.highwire.dtl.DTLVardef@1eccff8_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗