New perspective of small-molecule antiviral drugs development for RNA viruses.

High variability and adaptability of RNA viruses allows them to spread between humans and animals, causing large-scale infectious diseases which seriously threat human and animal health and social development. At present, AIDS, viral hepatitis and other viral diseases with high incidence and low cure rate are still spreading around the world. The outbreaks of Ebola, Zika, dengue and in particular of the global pandemic of COVID-19 have presented serious challenges to the global public health system. The development of highly effective and broad-spectrum antiviral drugs is a substantial and urgent research subject to deal with the current RNA virus infection and the possible new viral infections in the future. In recent years, with the rapid development of modern disciplines such as artificial intelligence technology, bioinformatics, molecular biology, and structural biology, some new strategies and targets for antivirals development have emerged. Here we review the main strategies and new targets for developing small-molecule antiviral drugs against RNA viruses through the analysis of the new drug development progress against several highly pathogenic RNA viruses, to provide clues for development of future antivirals.

Histone H1.2 Inhibited EMCV Replication through Enhancing MDA5-Mediated IFN-ß Signaling Pathway.

Histone H1.2 is a member of the linker histone family, which plays extensive and crucial roles not only in the regulation of chromatin dynamics, cell cycle, and cell apoptosis, but also in viral diseases and innate immunity response. Recently, it was discovered that H1.2 regulates interferon-ß and inhibits influenza virus replication, whereas its role in other viral infections is poorly reported. Here, we first found the up-regulation of H1.2 during Encephalomyocarditis virus (EMCV) infection, implying that H1.2 was involved in EMCV infection. Overexpression of H1.2 inhibited EMCV proliferation, whereas knockdown of H1.2 showed a significant promotion of virus infection in HEK293T cells. Moreover, we demonstrated that overexpression of H1.2 remarkably enhanced the production of EMCV-induced type I interferon, which may be the crucial factor for H1.2 proliferation-inhibitory effects. We further found that H1.2 up-regulated the expression of the proteins of the MDA5 signaling pathway and interacted with MDA5 and IRF3 in EMCV infection. Further, we demonstrated that H1.2 facilitated EMCV-induced phosphorylation and nuclear translocation of IRF3. Briefly, our research uncovers the mechanism of H1.2 negatively regulating EMCV replication and provides new insight into antiviral targets for EMCV.