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Sofosbuvir is a common therapy in hepatitis C virus infection, which targets the NS5B polymerase. Here, Smith et al. analyze the association between whole genome HCV polymorphisms and sofosbuvir treatment failure and identify three common polymorphisms present in non-targeted NS2 and NS3 proteins associated with reduced treatment response.

The circadian factors BMAL1/CLOCK and REV-ERB are master regulators of the human liver transcriptome but their role in hepatitis B virus infection is largely unknown. Here, Zhuang et al. show that REV-ERB regulates hepatitis B virus entry and BMAL1 directly binds HBV DNA and activates viral genome transcription.

The circadian clock can affect pathogen replication, but underlying molecular mechanisms are unclear. Here the authors demonstrate that the circadian components BMAL1 and REV-ERBα affect entry of hepatitis C virus (HCV) into hepatocytes and genome replication of HCV and related flaviviruses dengue and zika.

Abstract In the era of renewed space exploration, comprehending the effects of the space environment on human health, particularly for deep space missions, is crucial. While extensive research exists on the impacts of spaceflight, there is a gap regarding female reproductive risks. We hypothesize that space stressors could have enduring effects on female health, potentially increasing risks for future pregnancies upon return to Earth, particularly related to small-for-gestational-age (SGA) fetuses. To address this, we identify a shared microRNA (miRNA) signature between SGA and the space environment, conserved across humans and mice. These miRNAs target genes and pathways relevant to diseases and development. Employing a machine learning approach, we identify potential FDA-approved drugs to mitigate these risks, including estrogen and progesterone receptor antagonists, vitamin D receptor antagonists, and DNA polymerase inhibitors. This study underscores potential pregnancy-related health risks for female astronauts and proposes pharmaceutical interventions to counteract the impact of space travel on female health.