The productive infection of influenza A virus (IAV) depends on host factors. However, the involvement of long non-coding RNAs (lncRNAs) in IAV infection remains largely uninvestigated. In this work, we have discovered a human lncRNA, named lncRNA-PAAN (PA-associated noncoding RNA) that enhances IAV replication. The level of lncRNA-PAAN increases upon infection of IAV, but not other viruses, nor interferon treatment, suggesting specific up-regulation of lncRNA-PAAN expression by IAV. Silencing lncRNA-PAAN significantly decreases IAV replication through impairing the activity of viral RNA-dependent RNA polymerase (RdRp). This function of lncRNA-PAAN is a result of its association with viral PA protein, a key component of IAV RNA polymerase complex. Consequently, depletion of lncRNA-PAAN prevents the formation of functional RdRp. Together, these results suggest that lncRNA-PAAN promotes the assembly of viral RNA polymerase, thus warranting efficient viral RNA synthesis. Elucidating the functions of lncRNAs in IAV infection is expected to advance our understanding of IAV pathogenesis and open new avenues to the development of novel anti-IAV therapeutics.

Enterovirus 71 (EV71) is the major causative agent of hand, foot and mouth disease (HFMD) in children, causing severe clinical outcomes and even death. Here, we report an important role of the highly conserved alanine residue at position 107 in the capsid protein VP1 (VP1^A107) in the efficient replication of EV71. Substitutional mutations of VP1^A107 significantly diminish viral growth kinetics without significant effect on viral entry, expression of viral genes and viral production. The results of mechanistic studies reveal that VP1^A107 regulates the efficient cleavage of the VP0 precursor during EV71 assembly, which is required, in the next round of infection, for the transformation of the mature virion (160S) into an intermediate or A-particle (135S), a key step of virus uncoating. Furthermore, the results of molecular dynamic simulations and hydrogen-bond networks analysis of VP1^A107 suggest that flexibility of the VP1 BC loop or the region surrounding the VP1¹⁰⁷ residue directly correlates with viral infectivity. It is possible that sufficient flexibility of the region surrounding the VP1¹⁰⁷ residue favors VP0 conformational change that is required for the efficient cleavage of VP0 as well as subsequent viral uncoating and viral replication. Taken together, our data reveal the structural role of the highly conserved VP1^A107 in regulating EV71 maturation. Characterization of this novel determinant of EV71 virulence would promote the study on pathogenesis of Enteroviruses. Enterovirus 71 (EV71) causes hand, foot and mouth disease in children. In this work, we have discovered, for the first time, that the alanine residue at position 107 of the capsid protein VP1 (VP1^A107), which is present in almost all EV71 strains, plays an important role in the replication of EV71, since mutation of VP1^A107 significantly impairs viral growth. Detailed mechanistic studies reveal that VP1^A107 determines the efficient cleavage of the VP0 precursor during EV71 assembly, and subsequent virion uncoating in the next round of viral infection. We also observed that flexibility of the VP1 BC loop or the VP1^A107 region directly associates with viral infectivity. Collectively, our data suggest a structural role of the highly conserved VP1^A107 residue in regulating viral maturation, which is instrumental for the viral uncoating and viral replication. Discovery of this novel determinant of EV71 virulence would promote the study on pathogenesis of Enteroviruses.

The Chinese mitten crab, Eriocheir sinensis (H. Milne Edwards), is an important economic and widely cultivated aquaculture species in China. Under the requirements of health aquaculture, effective microorganisms (EM) have been widely introduced in E. sinensis culture. To date, however, we know little about the influence of EM on E. sinensis, especially in aspects of nutritional composition and flavour quality. Aiming to assess the comprehensive effects of EM on E. sinensis, we analysed the growth performance of E. sinensis after each moulting, examined the proximate composition, fatty acids, and flavour nucleotide composition of the edible tissues, as well as muscular amino acid composition in E. sinensis. In this study, we found EM could improve water quality by reducing total nitrogen and total phosphorus contents, while it had a weak promotion on the growth of crab. EM optimized the nutritional composition by improving the total lipid content in edible tissues, increasing beneficial fatty acid (C20:3) level in females and improving the nutritional value of muscular amino acid in males. Still, it caused a sweet taste loss by lowering the content of certain free amino acids especially Ala. However, EM increased umami or sweet taste contributors, that is AMP, GMP and IMP, and decreased off‐flavour contributors, that is Hx and HxR. Thus, the overall flavour quality of edible tissues in female crab was greatly improved by EM. The present study provides us multiple influences of EM on the crab aquaculture, and we recommend supplementing EM into the diet for crab aquaculture in the future.

Effect of Stocking Density on Growth, Serum Biochemical Parameters, Digestive Enzymes Activity and Antioxidant Status of Largemouth Bass, Micropterus salmoides

The effective antiviral agents that treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed around the world. The 3C-like protease (3CL^pro) of SARS-CoV-2 plays a pivotal role in virus replication; it also has become an important therapeutic target for the infection of SARS-CoV-2. In this work, we have identified Darunavir derivatives that inhibit the 3CL^pro through a high-throughput screening method based on a fluorescence resonance energy transfer (FRET) assay in vitro. We found that the compounds 29# and 50# containing polyphenol and caffeine derivatives as the P2 ligand, respectively, exhibited favorable anti-3CL^pro potency with EC50 values of 6.3 μM and 3.5 μM and were shown to bind to SARS-CoV-2 3CL^pro in vitro. Moreover, we analyzed the binding mode of the DRV in the 3CL^pro through molecular docking. Importantly, 29# and 50# exhibited a similar activity against the protease in Omicron variants. The inhibitory effect of compounds 29# and 50# on the SARS-CoV-2 3CL^pro warrants that they are worth being the template to design functionally improved inhibitors for the treatment of COVID-19.