Antiviral effects of ergosterol peroxide in a pig model of porcine deltacoronavirus (PDCoV) infection involves modulation of apoptosis and tight junction in the small intestine

Abstract

Porcine deltacoronavirus (PDCoV) is a newly discovered swine enteropathogenic coronavirus with worldwide distribution. However, efficient strategies to prevent or treat the infection remain elusive. Our in vitro study revealed that ergosterol peroxide (EP) from the mushroom Cryptoporus volvatus has efficient anti-PDCoV properties. The aim of this study is to evaluate the potential of EP as a treatment for PDCoV in vivo and elucidate the possible mechanisms. Seven-day-old piglets were infected with PDCoV by oral administration in the presence or absence of EP. Piglets infected with PDCoV were most affected, whereas administration of EP reduced diarrhea incidence, alleviated intestinal lesion, and decreased viral load in feces and tissues. EP reduced PDCoV-induced apoptosis and enhanced tight junction protein expressions in the small intestine, maintaining the integrity of the intestinal barrier. EP showed immunomodulatory effect by suppressing PDCoV-induced pro-inflammatory cytokines and the activation of IκBα and NF-κB p65, and upregulating IFN-I expression. Knockdown of p38 inhibited PDCoV replication and alleviated PDCoV-induced apoptosis, implying that EP inhibited PDCoV replication and alleviated PDCoV-induced apoptosis via p38/MAPK signaling pathway. Collectively, ergosterol peroxide can protect piglets from PDCoV, revealing the potential of EP for development as a promising strategy for treating and controlling the infection of PDCoV.

An Updated Review of Porcine Deltacoronavirus in Terms of Prevalence, Pathogenicity, Pathogenesis and Antiviral Strategy

“…However, different levels of PDCoV RNA were detected in multiple organs by RT-PCR. Although the strain and dose of the virus, the age of pigs or the time of euthanasia varied in different studies, PDCoV RNA was usually detected in the duodenum, jejunum, ileum, cecum, colon, liver, spleen, kidney, lung and MLN ( 2 , 12 , 39 – 41 , 45 ), and the quantities are relatively high in the duodenum, jejunum, ileum, cecum and colon. Low to moderate quantities of viral RNA are occasionally detected in the rectum, stomach, diaphragm, heart, inguinal lymph node, tonsil and muscle from rear leg ( 41 , 45 ).…”

“…Recently, our in vitro study found that PDCoV activates p38 signaling pathway to favor its replication ( 64 ). Later, we employed piglet models and illustrated that phosphorylated p38 levels in jejunum and ileum of PDCoV-infected piglets upregulated ( 2 ). Jeon et al confirmed that JNK1/2 and p38 were involved in the replication of PDCoV by affecting viral biosynthesis and progeny release ( 65 ).…”

“…NF-κB signaling pathway is a key mediator of cytokines and plays a central role in the host response to viral infection. PDCoV infection activates the NF-κB signaling pathway in vitro and in vivo ( 2 , 64 ). However, persistent activation of NF-κB signaling pathway can trigger inflammation by stimulating the expression of vast cytokines.…”

“…Porcine deltacoronavirus (PDCoV) is one of the most common enteropathogenic virus in the swine industry, causing typical clinical symptoms characterized by acute diarrhea, vomiting, dehydration and even death in piglets ( 1 , 2 ). It belongs to the genus Deltacoronavirus in the family Coronaviridae of the order Nidovirales ( 3 ).…”

Risk of spreading delta coronavirus to operating room personnel after COVID-19 vaccination

“…Dear Editor, porcine Delta Coronavirus (PDCoV), is a virus of the corona family of porcine enteropathogenic virus that was recently discovered and has a global pandemic. Therefore, effective strategies to prevent or treat infection remain unattainable [1]. It should be noted that the delta virus can increase the risk of admission to the hospital [2] and it seems that the rate of hospitalization due to this infection is up to twice as much as the previous infection [2] and increasing the hospital admission rate increases the pressure on the already exhausted health system and can put pressure on it [3].…”