Current hyaluronic acid (HA) hydrogel systems often cause cytotoxicity to encapsulated cells and lack the adhesive property required for effective localization of transplanted cells in vivo. In addition, the injection of hydrogel into certain organs (e.g., liver, heart) induces tissue damage and hemorrhage. In this study, we describe a bioinspired, tissue‐adhesive hydrogel that overcomes the limitations of current HA hydrogels through its improved biocompatibility and potential for minimally invasive cell transplantation. HA functionalized with an adhesive catecholamine motif of mussel foot protein forms HA‐catechol (HA‐CA) hydrogel via oxidative crosslinking. HA‐CA hydrogel increases viability, reduces apoptosis, and enhances the function of two types of cells (human adipose‐derived stem cells and hepatocytes) compared with a typical HA hydrogel crosslinked by photopolymerization. Due to the strong tissue adhesiveness of the HA‐CA hydrogel, cells are easily and efficiently transplanted onto various tissues (e.g., liver and heart) without the need for injection. Stem cell therapy using the HA‐CA hydrogel increases angiogenesis in vivo, leading to improved treatment of ischemic diseases. HA‐CA hydrogel also improved hepatic functions of transplanted hepatocytes in vivo. Thus, this bioinspired, tissue‐adhesive HA hydrogel can enhance the efficacy of minimally invasive cell therapy.

Hepatitis C virus (HCV) is a causative agent of chronic hepatitis and hepatocellular carcinoma. The core protein of HCV packages the viral RNA genome to form a nucleocapsid. In addition to its function as a structural protein, core protein is involved in regulation of cellular transcription, virus-induced transformation, and pathogenesis. To gain insights into cellular functions of the core protein by identification of cellular proteins interacting with the core protein, we employed a proteomic approach. Hepatocytes soluble cytoplasmic proteins were applied to the core proteins immobilized on Ni-nitrilotriacetic resin and total bound cellular proteins were resolved by 2-DE. Analyses of interacting proteins by matrix-assisted laser desorption/ionization-time of flight mass spectrometry allowed identification of 14 cellular proteins binding to the core protein. These proteins include DEAD-box polypeptide 5, similar in function to a known protein identified previously by yeast two-hybrid screening and 13 newly identified cellular proteins. Interestingly, nine protein spots were identified as intermediate microfilament proteins, including cytokeratins (five spots for cytokeratin 8, two for cytokeratin 19, and one for cytokeratin 18) and vimentin. Cytokeratin 8 and vimentin, which were previously shown to be involved in the infection processes of other viruses, were further analyzed to confirm their in vivo interactions with the core protein by immunoblotting and immunofluorescence microscopy. We discuss the functional implications of the interactions of the core protein with newly identified cellular proteins in HCV infection and pathogenesis.

Background We assessed the safety and immunogenicity of two recombinant DNA vaccines for COVID-19: GX-19 containing plasmid DNA encoding the SARS-CoV-2 spike protein, and GX-19N containing plasmid DNA encoding the SARS-CoV-2 receptor-binding domain (RBD) foldon, nucleocapsid protein, and plasmid DNA encoding the spike protein. Methods Two open-label non-randomised phase 1 trials, one of GX-19 and the other of GX-19N were done at two hospitals in South Korea. We enrolled healthy adults aged 19–49 years for the GX-19 trial and healthy adults aged 19–54 years for the GX-19N trial. Participants who tested positive by serological testing for SARS-CoV-2 were excluded. At 4-week intervals, the GX-19 trial participants received two vaccine doses (either 1·5 mg or 3·0 mg), and the GX-19N trial participants received two 3·0 mg doses. The vaccines were delivered intramuscularly using an electroporator. The participants were followed up for 52 weeks after first vaccination. Data collected up to day 57 after first vaccination were analysed in this interim analysis. The primary outcome was safety within 28 days after each vaccination measured in the intention-to-treat population. The secondary outcome was vaccine immunogenicity using blood samples collected on day 43 or 57 after first vaccination measured in the intention-to-treat population. The GX-19 ( NCT044445389 ) and GX-19N ( NCT04715997 ) trials are registered with ClinicalTrials.gov . Findings Between June 17 and July 30, 2020, we screened 97 individuals, of whom 40 (41%) participants were enrolled in the GX-19 trial (20 [50%] in the 1·5 mg group and 20 [50%] in the 3·0 mg group). Between Dec 28 and 31, 2020, we screened 23 participants, of whom 21 (91%) participants were enrolled on the GX-19N trial. 32 (52%) of 61 participants reported 80 treatment-emergent adverse events after vaccination. All solicited adverse events were mild except one (2%) case of moderate fatigue in the 1·5 mg GX-19 group; no serious vaccine-related adverse events were detected. Binding antibody responses increased after second dose of vaccination in all groups (p=0·0002 in the 1·5 mg GX-19 group; p<0·0001 in the 3·0 mg GX-19; and p=0·0004 for the spike protein and p=0·0001 for the RBD in the 3·0 mg GX-19N group). Interpretation GX-19 and GX-19N are safe and well tolerated. GX-19N induces humoral and broad SARS-CoV-2-specific T-cell responses. GX-19N shows lower neutralising antibody responses and needs improvement to enhance immunogenicity. Funding The Korea Drug Development Fund, funded by the Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare.

Many satellite RNAs (sat-RNAs) can attenuate or intensify the symptoms produced by their helper virus. Sat-RNA C, associated with turnip crinkle virus (TCV), was previously found to intensify the symptoms of TCV on all plants in which TCV produced visible symptoms. However, when the coat protein open reading frame (ORF) of TCV was precisely exchanged with that of cardamine chlorotic fleck virus, sat-RNA C attenuated the moderate symptoms of the chimeric virus when Arabidopsis plants were coinoculated with the chimeric virus. Symptom attenuation was correlated with a reduction in viral RNA levels in inoculated and uninoculated leaves. In protoplasts, the presence of sat-RNA C resulted in a reduction of approximately 70% in the chimeric viral genomic RNA at 44 hr postinoculation, whereas the sat-RNA wa consistently amplified to higher levels by the chimeric virus than by wild-type TCV. TCV with a deletion of the coat protein ORF also resulted in a similar increase in sat-RNA C levels in protoplasts, indicating that the TVC coat protein, or its ORF, downregulates the synthesis of sat-RNA C. These results suggest that the coat protein or its ORF is a viral determinant for symptom modulation by sat-RNA C, and symptom attenuation is at least partly due to inhibition of virus accumulation.

In spite of the large number of repositioned drugs and direct-acting antivirals in clinical trials for the management of the ongoing COVID-19 pandemic, there are few cost-effective therapeutic options for severe acute respiratory syndrome (SARS) coronavirus 2 (SCoV2) infection. In this paper, we show that xanthorrhizol (XNT), a bisabolane-type sesquiterpenoid compound isolated from the Curcuma xanthorrhizza Roxb., a ginger-line plant of the family Zingiberaceae, displays a potent antiviral efficacy in vitro against SCoV2 and other related coronaviruses, including SARS-CoV-1 (SCoV1) and a common cold-causing human coronavirus. XNT reduced infectious SCoV2 titer by ~3-log10 at 20 μM and interfered with the replication of the SCoV1 subgenomic replicon, while it had no significant antiviral effects against hepatitis C virus and noroviruses. Further, XNT exerted similar antiviral functions against SCoV2 variants, such as a GH clade strain and a delta strain currently predominant worldwide. Neither SCoV2 entry into cells nor the enzymatic activity of viral RNA polymerase (Nsp12), RNA helicase (Nsp13), or the 3CL main protease (Nsp5) was inhibited by XNT. While its CoV replication inhibitory mechanism remains elusive, our results demonstrate that the traditional folk medicine XNT could be a promising antiviral candidate that inhibits a broad range of SCoV2 variants of concern and other related CoVs.