The Prevalence and Evolutionary Characteristics of Bovine Coronavirus in China (preprint)

Four viral intestinal pathogens such as bovine coronavirus (BCoV), bovine rotavirus (BRV), bovine viral diarrhea virus (BVDV) and bovine astrovirus (BoAstV) are the most common causes of adult cattle diarrhea. In this study, 797 samples were collected from January 2020 to February 2023. Among them, BCoV is major pathogen we detected and the positive rate was 48.18% (471/794). Farther more, among 307 diarrhea samples and 487 asymptomatic samples, 159 and 312 were BCoV positive, respectively. The results reveal that BCoV is associated with bovine diarrhea (p=0.001). In addition, we also amplified and analyzed Hemagglutinin-esterase (HE), Spike (S) and whole genome of partially positive sample. Getting 8 HE complete sequence, 8 S complete sequence and 5 whole genomes. The molecular characterization provides reveal that 5 strains were branched Chinese strains, Japan and part of American strains in GⅡb，and Korea strains branched in GⅡa. BCoV-Neimeng S in this study was mutated 143H/A to 143R, which is uncommon in S gene. As a residue on the side chain of the core binding site of S1-NTD, this mutation changed the tertiary structure and may be possible to affect the glycoside binding spectrum. The noteworthy that BCoV-SJZ2 and BCoV-YZ1 have four amino acid insertions on HE, which is the same as SWUN/A10/2018. We also analysis 4.8kDa and 4.9kDa non-structural protein large-scale truncation and membrane protein mutation. This article will discuss epidemiology and genome analysis.

Global dynamics of Porcine Epidemic Diarrhea Virus evolution and transmission (preprint)

With a possible origin from bats, the alphacoronavirus Porcine epidemic diarrhea virus (PEDV) causes significant hazards and widespread epidemics in the swine population. However, the ecology, evolution, and spread of PEDV are still unclear. Here, from 149,869 fecal and intestinal tissue samples of pigs collected in an 11-year survey, we identified PEDV as the most dominant virus in diarrheal animals. Global whole genomic and evolutionary analyses of 672 PEDV strains revealed the fast-evolving PEDV genotype 2 (G2) strains as the main epidemic viruses worldwide, which seems to correlate with the use of G2-targeting vaccines. The evolving pattern of the G2 viruses presents geographic bias as they evolve tachytely in South Korea but undergo the highest recombination in China. Therefore, we clustered six PEDV haplotypes in China, whereas South Korea held five haplotypes, including a unique haplotype G. In addition, an assessment of the spatiotemporal spread route of PEDV indicates Germany and Japan as the primary hubs for PEDV dissemination in Europe and Asia, respectively. Overall, our findings provide novel insights into the epidemiology, evolution, and transmission of PEDV, and thus may lay a foundation for the prevention and control of PEDV and other coronaviruses.

Reanalysis of MERS, SARS and COVID-19 Infection Datasets using VirOmics Playground Reveals Common Patterns in Gene and Protein Expression (preprint)

Three lethal lower respiratory tract coronavirus epidemics have occurred over the past 20 years. This coincided with major developments in genome-wide gene and protein expression analysis, resulting in a wealth of datasets in the public domain. Seven such in vitro studies were selected for comparative bioinformatic analysis through the VirOmics Playground, a user-friendly visualisation and exploration platform we recently developed. Despite the heterogeneous nature of the data sets, several commonalities could be observed across studies and species. Differences, on the other hand, reflected not only variations between species, but also other experimental variables, such as cell lines used for the experiments, infection protocols and potential discrepancies between transcriptome and proteome data. The results presented here are available online and can be replicated through the VirOmics Playground.

SARS-CoV-2 and Malayan pangolin coronavirus infect human endoderm, ectoderm and induced lung progenitor cells (preprint)

Since the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in several somatic cells, little is known about the infection of SASRS-CoV-2 and its related pangolin coronavirus (GX_P2V). Here we present for the first time that SARS-CoV-2 pseudovirus and GX_P2V could infect lung progenitor and even anterior foregut endoderm cells causing these cells death, which differentiated from human embryonic stem cells (hESCs). The infection and replication of SARS-CoV-2 and GX_P2V were inhibited when treated with whey protein of breastmilk and Remdesivir, confirming that these two viruses could infect lung progenitor and even anterior foregut endoderm. Moreover, we found that SARS-CoV-2 pseudovirus could infect endoderm and ectoderm. We found that whey protein blocked SARS-CoV-2 infecting these cells. In line with the SARS-CoV-2 results, GX_P2V could also infected endoderm and ectoderm, and also was inhibited by Remdesivir treatment. Although expressing coronavirus related receptor such as ACE2 and TMPRSS2, mesoderm cells are not permissive for SARS-CoV-2 and GX_P2V infection, which needed further to study the mechanisms. Interestingly, we also found that hESCs, which also express ACE2 and TMPRSS2 markers, are permissive for GX_P2V but not SARS-CoV-2 pseudovirus infection and replication, indicating the widespread cell types for GX_P2V infection. Heparin treatment blocked efficiently viral infection. These results provided insight that these stem cells maybe provided a stable repository of coronavirus function or genome. The potential consequence of SARS-CoV-2 and animal coronavirus such as GX_P2V infection in hESCs, germ layer and induced progenitors should be closely monitored.

Nitazoxanide and JIB-04 have broad-spectrum antiviral activity and inhibit SARS-CoV-2 replication in cell culture and coronavirus pathogenesis in a pig model (preprint)

Pathogenic coronaviruses represent a major threat to global public health. Here, using a recombinant reporter virus-based compound screening approach, we identified several small-molecule inhibitors that potently block the replication of the newly emerged severe acute respiratory syndrome virus 2 (SARS-CoV-2). Two compounds, nitazoxanide and JIB-04 inhibited SARS-CoV-2 replication in Vero E6 cells with an EC50 of 4.90 M and 0.69 M, respectively, with specificity indices of greater than 150. Both inhibitors had in vitro antiviral activity in multiple cell types against some DNA and RNA viruses, including porcine transmissible gastroenteritis virus. In an in vivo porcine model of coronavirus infection, administration of JIB-04 reduced virus infection and associated tissue pathology, which resulted in improved body weight gain and survival. These results highlight the potential utility of nitazoxanide and JIB-04 as antiviral agents against SARS-CoV-2 and other viral pathogens.