The giant panda (Ailuropoda melanoleuca) is a vulnerable mammal herbivore living wild in central China. Viral infections have become a potential threat to the health of these endangered animals, but limited information related to these infections is available. Using a viral metagenomic approach, we surveyed viruses in the feces, nasopharyngeal secretions, blood, and different tissues from a wild giant panda that died from an unknown disease, a healthy wild giant panda, and 46 healthy captive animals. The previously uncharacterized complete or near complete genomes of four viruses from three genera in Papillomaviridae family, six viruses in a proposed new Picornaviridae genus (Aimelvirus), two unclassified viruses related to posaviruses in Picornavirales order, 19 anelloviruses in four different clades of Anelloviridae family, four putative circoviruses, and 15 viruses belonging to the recently described Genomoviridae family were sequenced. Reflecting the diet of giant pandas, numerous insect virus sequences related to the families Iflaviridae, Dicistroviridae, Iridoviridae, Baculoviridae, Polydnaviridae, and subfamily Densovirinae and plant viruses sequences related to the families Tombusviridae, Partitiviridae, Secoviridae, Geminiviridae, Luteoviridae, Virgaviridae, and Rhabdoviridae; genus Umbravirus, Alphaflexiviridae, and Phycodnaviridae were also detected in fecal samples. A small number of insect virus sequences were also detected in the nasopharyngeal secretions of healthy giant pandas and lung tissues from the dead wild giant panda. Although the viral families present in the sick giant panda were also detected in the healthy ones, a higher proportion of papillomaviruses, picornaviruses, and anelloviruses reads were detected in the diseased panda. This viral survey increases our understanding of eukaryotic viruses in giant pandas and provides a baseline for comparison to viruses detected in future infectious disease outbreaks. The similar viral families detected in sick and healthy giant pandas indicate that these viruses result in commensal infections in most immuno-competent animals.

Chapparvovirus, a recently determined new genus in the family Parvoviridae, can infect many species of animals including bats, chickens, and pigs. Here, using viral metagenomics method, we identified a novel Chapparvovirus from feces of wild rats and designated it as rat parvovirus 2 (RPV2). The nearly complete genome of RPV2 is 4222-nt long and includes two ORFs encoding a 654-aa nonstructural protein 1 (NS1) and a 472-aa capsid protein (VP), respectively. Phylogenetic analysis over the amino acid sequence of the NS1 showed that RPV2 clustered with Eidolon helvum parvovirus 2 (EHPV2), porcine parvovirus 7 (PPV7), and turkey parvovirus 1 (TP1), forming a separate clade. Sequence analysis indicated that the NS1 protein of RPV2 shared the highest amino acid sequence identity (51 %) with that of EHPV2. According to the genetic distance-based criteria, RPV2 identified here belongs to a novel species of Chapparvovirus.

The number of members in the genus Gammapapillomavirus of Family Papillomaviridae has recently been expanding most rapidly. The aim of this study was to characterize a novel human gammapapillomavirus type identified in a vaginal swab from a 25-year-old pregnant woman suffering from vaginitis. Viral metagenomics method was used to detect the viral sequences in 88 vaginal swab samples collected from 88 pregnant women with vaginitis. A novel papillomavirus, named HPV-ZJ01 (GenBank no. KX082661), was detected in one sample and its complete genome sequence was amplified by PCR and sequenced by Sanger walking. Phylogenetic analyses based on the complete genome and the L1 protein of HPV-ZJ01 and other representative human papillomaviruses were done, respectively. Further PCR screening was performed in vaginal swabs (n = 135), cervical smears (n = 40) and cervical cancer tissues (n = 40) using nested-PCR primers designed based on HPV-ZJ01 sequence to investigate the prevalence of HPV-ZJ01. The genome of HPV-ZJ01 is 7,358 bp in length with a GC content of 37.8 %. HPV-ZJ01 was predicted to contain six open reading frames (E6, E7, E1, E2, L2, and L1) and a non-coding long control region (LCR). The genome shared the highest overall similarity to HPV-166, with 70.6 % nucleotide sequence identity while its L1 gene shared the highest nucleotide similarity to HPV-162, with 71.1 % sequence identity. Phylogenetic analysis suggested that HPV-ZJ01 belongs to a novel HPV type in the Gamma-PV genus, species Gamma-19, already containing HPV161, HPV162 and HPV166. PCR screening results indicated that none of the other samples were positive for HPV-ZJ01 except the original HPV-ZJ01 positive vaginal swab specimen. The genome sequence of a novel type of species Gamma-19 HPV was characterized. The screening PCR results suggested that HPV-ZJ01 is not associated with any of the cervical cancer samples tested. In order to confirm the prevalence and disease association, if any, for HPV-ZJ01, a further study with different sample types and a larger sample size is needed.

Central nervous system diseases are highly complex in terms of etiology and pathogenesis, making their treatment and interventions for them a major focus and challenge in neuroscience research. Anthocyanins, natural water-soluble pigments widely present in plants, belong to the class of flavonoid compounds. As natural antioxidants, anthocyanins have attracted extensive attention due to their significant functions in scavenging free radicals, antioxidation, anti-inflammation, and anti-apoptosis. The application of anthocyanins in the field of central nervous system injury, particularly in neurodegenerative diseases, neurotoxicity induced by chemical drugs, stress-related nerve damage, and cerebrovascular diseases, has achieved remarkable research outcomes. However, anthocyanins often exhibit low chemical stability, a short half-life, and relatively low bioavailability, which limit their clinical application. Recent studies have found that the stability and bioavailability of anthocyanins can be significantly improved through nanoencapsulation, acylation, and copigmentation, as well as the preparation of nanogels, nanoemulsions, and liposomes. These advancements offer the potential for the development of anthocyanins as a new type of neuroprotective agent. Future research will focus on the innovative design of nano-delivery systems and structural modification based on artificial intelligence. Such research is expected to break through the bottleneck of anthocyanin application and enable it to become a core component of next-generation intelligent neuroprotective agents.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes 2019 coronavirus disease (COVID-19), poses a significant threat to global public health security. Like other coronaviruses, SARS-CoV-2 has developed various strategies to inhibit the production of interferon (IFN). Here, we have discovered that SARS-CoV-2 Nsp15 obviously reduces the expression of IFN-β and IFN-stimulated genes (ISG56, CXCL10), and also inhibits IRF3 phosphorylation and nuclear translocation by antagonizing the RLR-mediated antiviral signaling pathway. Mechanically, we found that the poly-U-specific endonuclease domain (EndoU) of Nsp15 directly associates with the kinase domain (KD) of TBK1 to interfere TBK1 interacting with IRF3 and the flowing TBK1-mediated IRF3 phosphorylation. Furthermore, Nsp15 also prevented nuclear translocation of phosphorylated IRF3 via binding to the nuclear import adaptor karyopherin α1 (KPNA1) and promoting it autophagy-dependent degradation. These findings collectively reveal a novel mechanism by which Nsp15 antagonizes host’s innate immune response.

The outbreaks caused by RNA and DNA viruses, such as SARS-CoV-2 and monkeypox, pose serious threats to human health. The RLR and cGAS-STING pathways contain major cytoplasmic sensors and signaling transduction axes for host innate antiviral immunity. In physiological and virus-induced pathological states, the activation and inactivation of these signal axes are tightly controlled, especially post-translational modifications (PTMs). E3 ubiquitin ligases (E3s) are the direct manipulator of ubiquitin codons and determine the type and modification type of substrate proteins. Therefore, members of the E3s family are involved in balancing the host’s innate antiviral immune responses, and their functions have been extensively studied over recent decades. In this study, we overviewed the mechanisms of different members of three E3s families that mediate the RLR and cGAS-STING axes and analyzed them as potential molecular targets for the prevention and treatment of virus-related diseases.