Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. The virus still spreads globally through human-to-human transmission. Nevertheless, there are no specific treatments clinically approved. This study aimed to compare antiviral activity of gemcitabine and its analogue 2′-fluoro-2′-deoxycytidine (2FdC) against SARS-CoV-2 as well as cytotoxicity in vitro. Fluorescent image-based antiviral assays revealed that gemcitabine was highly potent, with a 50% effective concentration (EC₅₀) of 1.2 μM, more active than the well-known nucleoside monophosphate remdesivir (EC₅₀ = 35.4 μM). In contrast, 2FdC was marginally active (EC₅₀ = 175.2 μM). For all three compounds, the 50% cytotoxic concentration (CC₅₀) values were over 300 μM toward Vero CCL-81 cells. Western blot and quantitative reverse-transcription polymerase chain reaction analyses verified that gemcitabine blocked viral protein expression in virus-infected cells, not only Vero CCL-81 cells but also Calu-3 human lung epithelial cells in a dose-dependent manner. It was found that gemcitabine has a synergistic effect when combined with remdesivir. This report suggests that the difluoro group of gemcitabine is critical for the antiviral activity and that its combination with other evaluated antiviral drugs, such as remdesivir, could be a desirable option to treat SARS-CoV-2 infection.

The ubiquitin-proteasome system (UPS) has been recognized for regulating fundamental cellular processes, followed by induction of proteasomal degradation of target proteins, and triggers multiple signaling pathways that are crucial for numerous aspects of cellular physiology. Especially tripartite motif (TRIM) proteins, well-known E3 ubiquitin ligases, emerge as having critical roles in several antiviral signaling pathways against varying viral infections. Here we highlight recent advances in the study of antiviral roles of TRIM proteins toward influenza virus infection in terms of the modulation of pathogen recognition receptor (PRR)-mediated innate immune sensing, direct obstruction of influenza viral propagation, and participation in virus-induced autophagy.

The emergence of numerous SARS-CoV-2 variants, characterized by mutations in the viral RNA genome and target proteins, has presented challenges for accurate COVID-19 diagnosis. To address this, we developed universal aptamer probes capable of binding to the spike proteins of SARS-CoV-2 variants, including highly mutated strains like Omicron. These aptamers were identified through protein-based SELEX using spike proteins from three key variants (D614G-substituted Wuhan-Hu-1, Delta, and Omicron) and virus-based SELEX, known as viro-SELEX. Leveraging these universal aptamers, we created a highly sensitive lateral flow assay (LFA) and an ultra-sensitive molecular diagnostic platform that integrates a novel rapid PCR technique, enabling fast and reliable detection across all SARS-CoV-2 variants.