Influenza virus is a highly contagious zoonotic respiratory disease that causes seasonal outbreaks each year and unpredictable pandemics occasionally with high morbidity and mortality rates, posing a great threat to public health worldwide. Besides the limited effect of vaccines, the problem is exacerbated by the lack of drugs with strong antiviral activity against all flu strains. Currently, there are two classes of antiviral drugs available that are chemosynthetic and approved against influenza A virus for prophylactic and therapeutic treatment, but the appearance of drug-resistant virus strains is a serious issue that strikes at the core of influenza control. There is therefore an urgent need to develop new antiviral drugs. Many reports have shown that the development of novel bioactive plant extracts and microbial extracts has significant advantages in influenza treatment. This paper comprehensively reviews the development and effects of chemosynthetic drugs, plant extracts, and microbial extracts with influenza antiviral activity, hoping to provide some references for novel antiviral drug design and promising alternative candidates for further anti-influenza drug development.

Studies have shown that long noncoding RNAs (lncRNAs) play crucial roles in regulating virus infection, host immune response, and other biological processes. Although some lncRNAs have been reported to be involved in antiviral immunity, many lncRNAs have unknown functions in interactions between the host and various viruses, especially influenza A virus (IAV). Herein, we demonstrate that the expression of lncRNA LINC02574 can be induced by IAV infection. Treatment with viral genomic RNA, poly (I:C), or interferons (IFNs) significantly stimulated LINC02574 expression, while RIG-I knockdown and IFNAR1 knockout significantly decreased LINC02574 expression after viral infection or IFN treatment. In addition, inhibition of LINC02574 expression in A549 cells enhanced IAV replication, while overexpression of LINC02574 inhibited viral production. Interestingly, knockdown of LINC02574 attenuated the expression of type I and type III IFNs and multiple ISGs, as well as the activation of STAT1 triggered by IAV infection. Moreover, LINC02574 deficiency impaired the expression of RIG-I, TLR3, and MDA5, and decreased the phosphorylation level of IRF3. In conclusion, the RIG-I-dependent interferon signaling pathway can induce LINC02574 expression. Moreover, the data reveal that LINC02574 inhibits IAV replication by positively regulating the innate immune response.

Long non-coding RNAs (lncRNAs) have been recognized for their crucial roles in the replication processes of various viruses. However, the specific functions and regulatory mechanisms of many lncRNAs in influenza A virus (IAV) pathogenesis remain poorly understood. In this study, we identified lncRNA THRIL and observed a significant reduction in its expression following IAV infection in A549 cells. The treatment of cells with the viral mimic poly (I:C), or with type I and type III interferons, resulted in a substantial decrease in THRIL expression. Furthermore, THRIL overexpression significantly enhanced IAV replication, while its silencing markedly reduced IAV replication. Additionally, IAV infection led to notable reductions in the expression levels of type I and type III interferons in cell lines overexpressing THRIL compared to control groups; conversely, cell lines with THRIL knockdown exhibited significantly higher interferon levels than control groups. Moreover, THRIL was found to inhibit the expression of several critical interferon-stimulated genes (ISGs), which are essential for an effective antiviral response. Notably, our findings demonstrated that THRIL impaired the activation of IRF3, a key transcription factor in the interferon signaling pathway, thereby suppressing host innate immunity. These results highlight THRIL’s potential as a therapeutic target for antiviral strategies.