The recent experience with SARS-COV-2 has raised our alarm about the cross-species transmissibility of coronaviruses and the emergence of new coronaviruses. Knowledge of this family of viruses needs to be constantly updated. Porcine deltacoronavirus (PDCoV), a newly emerging member of the genus Deltacoronavirus in the family Coronaviridae, is a swine enteropathogen that causes diarrhea in pigs and may lead to death in severe cases. Since PDCoV diarrhea first broke out in the United States in early 2014, PDCoV has been detected in many countries, such as South Korea, Japan and China. More importantly, PDCoV can also infect species other than pigs, and infections have even been reported in children, highlighting its potential for cross-species transmission. A thorough and systematic knowledge of the epidemiology and pathogenesis of PDCoV will not only help us control PDCoV infection, but also enable us to discover the common cellular pathways and key factors of coronaviruses. In this review, we summarize the current knowledge on the prevalence, pathogenicity and infection dynamics, pathogenesis and immune evasion strategies of PDCoV. The existing anti-PDCoV strategies and corresponding mechanisms of PDCoV infection are also introduced, aiming to provide suggestions for the prevention and treatment of PDCoV and zoonotic diseases.

Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus that causes severe watery diarrhea in piglets with high morbidity and mortality, resulting in serious economic losses to the farming industry. Ergosterol peroxide (EP) is a sterol with diverse biological activities including antiviral activity. In this study, we explored whether EP extracted from the fruiting body of the mushroom Cryptoporus volvatus had the potential to inhibit PEDV infection in Vero cells. The results revealed that EP had a remarkable inhibitory effect on PEDV infection. It could significantly inhibit multiple stages of the PEDV life cycle, including internalization, replication and release, and could directly inactivate PDCoV infectivity. However, it did not affect PEDV attachment. Furthermore, EP alleviated PEDV-induced apoptosis and mitigated the decrease in mitochondrial membrane potential caused by PEDV infection. It suppressed ROS generation and p53 activation caused by PEDV infection. The ROS scavenger N-acetyl-l-cysteine (NAC) and the p53 specific inhibitor Pifithrin-α (PFT-α) suppressed PEDV-induced apoptosis and impeded viral replication, suggesting that ROS and p53 play an important role in PEDV-induced apoptosis and viral replication. Collectively, EP can prevent PEDV internalization, replication and release, possesses the ability to directly inactivate PEDV, and can inhibit PEDV-induced apoptosis by interfering with PEDV-induced ROS production and p53 activation. These findings highlight the therapeutic potential of EP against PEDV infection.

Pig diarrhea is a universal problem in the process of pig breeding, which seriously affects the development of the pig industry. Porcine enteric coronaviruses (PECoVs) are common pathogens causing diarrhea in pigs, currently including transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV) and swine acute diarrhea syndrome coronavirus (SADS-CoV). With the prosperity of world transportation and trade, the spread of viruses is becoming wider and faster, making it even more necessary to prevent PECoVs. In this paper, the host factors required for the efficient replication of these CoVs and the compounds that exhibit inhibitory effects on them were summarized to promote the development of drugs against PECoVs. This study will be also helpful in discovering general host factors that affect the replication of CoVs and provide references for the prevention and treatment of other CoVs.

Bovine viral diarrhea virus (BVDV) is one of the most important etiological agents that causes serious economic losses to the global livestock industry. Vaccines usually provide limited efficacy against BVDV due to the emergence of mutant strains. Therefore, developing novel strategies to combat BVDV infection is urgently needed. Bergamottin (Berg), a natural furanocoumarin compound, possesses various pharmaceutical bioactivities, but its effect on BVDV infection remains unknown. The present study aimed to investigate the antiviral effect and underlying mechanism of Berg against BVDV infection. The results showed that Berg exhibited an inhibitory effect on BVDV replication in MDBK cells by disrupting the viral replication and release, rather than directly inactivating virus particles. Mechanistically, Berg inhibits BVDV replication by suppressing endoplasmic reticulum (ER) stress-mediated apoptosis via reducing reactive oxygen species (ROS) generation. Studies in vivo demonstrated that oral gavage of Berg at doses of 50 mg/kg and 75 mg/kg significantly reduced the viral load within the intestines and spleen in BVDV-challenged mice. Furthermore, histopathological damage and oxidative stress caused by BVDV were also mitigated with Berg treatment. Our data indicated that Berg suppressed BVDV propagation both in vitro and in vivo, suggesting it as a promising antiviral option against BVDV.

25-Hydroxycholesterol (25HC) is a hydroxylated cholesterol with multiple antiviral activities, however, little is known about the mechanisms by which 25HC correlates antiviral ability with lipid droplet (LD) dynamic balance to ensure cholesterol homeostasis. In the present study, 25HC was applied to porcine deltacoronavirus (PDCoV)-infected LLC-PK1 (Lilly Laboratories Culture-Porcine Kidney 1) cells and piglets to explore its antiviral capacity and underlying mechanism. The results revealed that 25HC decreased free cholesterol (FC) levels but increased triglyceride (TG) levels in PDCoV-infected cells and piglets. The accumulation of LDs induced by oleic acid (OA) impedes PDCoV replication. In addition, 25HC administration increases LD accumulation and declines protein expression associated with lipophagy and lysosomes to facilitate LD accumulation. Moreover, 25HC inhibited TFEB (transcription factor-EB) expression, blocked its translocation into the nucleus and reversed Mechanistic Target of Rapamycin Complex 1 (mTORC1) activity, which in turn hindered lipophagy and PDCoV replication. Additionally, 25HC treatment ameliorated the clinical symptoms and intestinal injury of PDCoV-infected piglets. These findings reveal the beneficial effect of lipophagy on PDCoV infection and uncover the antiviral mechanism of 25HC, by which lipophagy and mTOR activity are tightly controlled by 25HC. Graphical Abstract