-
Viruses Feb 2024This review presents comparative information corresponding to the progress in knowledge of some aspects of infection by the porcine epidemic diarrhea virus (PEDV) and... (Review)
Review
This review presents comparative information corresponding to the progress in knowledge of some aspects of infection by the porcine epidemic diarrhea virus (PEDV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronaviruses. PEDV is an alphacoronavirus of great economic importance due to the million-dollar losses it generates in the pig industry. PEDV has many similarities to the SARS-CoV-2 betacoronavirus that causes COVID-19 disease. This review presents possible scenarios for SARS-CoV-2 based on the collected literature on PEDV and the tools or strategies currently developed for SARS-CoV-2 that would be useful in PEDV research. The speed of the study of SARS-CoV-2 and the generation of strategies to control the pandemic was possible due to the knowledge derived from infections caused by other human coronaviruses such as severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). Therefore, from the information obtained from several coronaviruses, the current and future behavior of SARS-CoV-2 could be inferred and, with the large amount of information on the virus that causes COVID-19, the study of PEDV could be improved and probably that of new emerging and re-emerging coronaviruses.
Topics: Humans; Animals; Swine; SARS-CoV-2; Porcine epidemic diarrhea virus; COVID-19
PubMed: 38400014
DOI: 10.3390/v16020238 -
Virology Journal Aug 2023Although three years after the outbreak of SARS-CoV-2, the virus is still having a significant impact on human health and the global economy. Infection through...
Development and efficacy assessment of hand sanitizers and polylactic acid films incorporating caffeic acid and vanillin for enhanced antiviral properties against HCoV-229E.
BACKGROUND
Although three years after the outbreak of SARS-CoV-2, the virus is still having a significant impact on human health and the global economy. Infection through respiratory droplets is the main transmission route, but the transmission of the virus by surface contact cannot be ignored. Hand sanitizers and antiviral films can be applied to control SARS-CoV-2, but sanitizers and films show drawbacks such as resistance of the virus against ethanol and environmental problems including the overuse of plastics. Therefore, this study suggested applying natural substrates to hand sanitizers and antiviral films made of biodegradable plastic (PLA). This approach is expected to provide advantages for the easy control of SARS-CoV-2 through the application of natural substances.
METHODS
Antiviral disinfectants and films were manufactured by adding caffeic acid and vanillin to ethanol, isopropyl alcohol, benzalkonium chloride, and PLA. Antiviral efficacies were evaluated with slightly modified international standard testing methods EN 14,476 and ISO 21,702.
RESULTS
In suspension, all the hand sanitizers evaluated in this study showed a reduction of more than 4 log within 2 min against HCoV-229E. After natural substances were added to the hand sanitizers, the time needed to reach the detection limit of the viral titer was shortened both in suspension and porcine skin. However, no difference in the time needed to reach the detection limit of the viral titer was observed in benzalkonium chloride. In the case of antiviral films, those made using both PLA and natural substances showed a 1 log reduction of HCoV-229E compared to the neat PLA film for all treatment groups. Furthermore, the influence of the organic load was evaluated according to the number of contacts of the antiviral products with porcine skin. Ten rubs on the skin resulted in slightly higher antiviral activity than 50 rubs.
CONCLUSION
This study revealed that caffeic acid and vanillin can be effectively used to control HCoV-229E for hand sanitizers and antiviral films. In addition, it is recommended to remove organic matter from the skin for maintaining the antiviral activity of hand sanitizer and antiviral film as the antiviral activity decreased as the organic load increased in this study.
Topics: Humans; Swine; Animals; Hand Sanitizers; Coronavirus 229E, Human; Antiviral Agents; Benzalkonium Compounds; COVID-19; SARS-CoV-2; Polyesters; Ethanol
PubMed: 37641064
DOI: 10.1186/s12985-023-02159-z -
Journal of Virology Feb 2024The eukaryotic translation initiation factor eIF4E can regulate cellular translation via phosphorylation on serine 209. In a recent study, by two rounds of TMT relative...
The eukaryotic translation initiation factor eIF4E can regulate cellular translation via phosphorylation on serine 209. In a recent study, by two rounds of TMT relative quantitative proteomics, we found that phosphorylated eIF4E (p-eIF4E) favors the translation of selected mRNAs, and the encoded proteins are mainly involved in ECM-receptor, focal adhesion, and PI3K-Akt signaling. The current paper is focused on the relationship between p-eIF4E and the downstream host cell proteins, and their presumed effect on efficient entry of PEDV. We found that the depletion of membrane-residential factor TSPAN3, CD63, and ITGB2 significantly inhibited viral invasion of PEDV, and reduced the entry of pseudotyped particles PEDV-pp, SARS-CoV-pp, and SARS-CoV-2-pp. The specific antibodies of TSPAN3, CD63, and ITGB2 blocked the adsorption of PEDV into host cells. Moreover, we detected that eIF4E phosphorylation was increased at 1 h after PEDV infection, in accordance with the expression of TSPAN3, CD63, and ITGB2. Similar trends appeared in the intestines of piglets in the early stage of PEDV challenge. Compared with Vero cells, S209A-Vero cells in which eIF4E cannot be phosphorylated showed a decrease of invading PEDV virions. MNK kinase inhibitor blocked PEDV invasion, as well as reduced the accumulation of TSPAN3, CD63, and ITGB2. Further study showed that the ERK-MNK pathway was responsible for the regulation of PEDV-induced early phosphorylation of eIF4E. This paper demonstrates for the first time the connections among p-eIF4E stimulation and membrane-residential host factors. Our findings also enrich the understanding of the biological function of phosphorylated eIF4E during the viral life cycle.IMPORTANCEThe eukaryotic translation initiation factor eIF4E can regulate cellular translation via phosphorylation. In our previous study, several host factors susceptible to a high level of p-eIF4E were found to be conducive to viral infection by coronavirus PEDV. The current paper is focused on cell membrane-residential factors, which are involved in signal pathways that are sensitive to phosphorylated eIF4E. We found that the ERK-MNK pathway was activated, which resulted in the stimulation of phosphorylation of eIF4E in early PEDV infection. Phospho-eIF4E promoted the viral invasion of PEDV by upregulating the expression of host factors TSPAN3, CD63, and ITGB2 at the translation level rather than at the transcription level. Moreover, TSPAN3, CD63, or ITGB2 facilitates the efficient entry of coronavirus SARS-CoV, SARS-CoV-2, and HCoV-OC43. Our findings broaden our insights into the dynamic phosphorylation of eIF4E during the viral life cycle, and provide further evidence that phosphorylated eIF4E regulates selective translation of host mRNA.
Topics: Animals; Cell Membrane; Chlorocebus aethiops; Eukaryotic Initiation Factor-4E; Extracellular Signal-Regulated MAP Kinases; Integrin beta Chains; Phosphatidylinositol 3-Kinases; Phosphorylation; Porcine epidemic diarrhea virus; Protein Biosynthesis; Protein Serine-Threonine Kinases; Proteomics; RNA, Messenger; Swine; Tetraspanins; Vero Cells; Virus Internalization
PubMed: 38299843
DOI: 10.1128/jvi.01948-23 -
Antimicrobial Agents and Chemotherapy Mar 2024Libraries composed of licensed drugs represent a vast repertoire of molecules modulating physiological processes in humans, providing unique opportunities for the...
Libraries composed of licensed drugs represent a vast repertoire of molecules modulating physiological processes in humans, providing unique opportunities for the discovery of host-targeting antivirals. We screened the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) repurposing library with approximately 12,000 molecules for broad-spectrum coronavirus antivirals and discovered 134 compounds inhibiting an alphacoronavirus and mapping to 58 molecular target categories. Dominant targets included the 5-hydroxytryptamine receptor, the dopamine receptor, and cyclin-dependent kinases. Gene knock-out of the drugs' host targets including cathepsin B and L (CTSB/L; VBY-825), the aryl hydrocarbon receptor (AHR; Phortress), the farnesyl-diphosphate farnesyltransferase 1 (FDFT1; P-3622), and the kelch-like ECH-associated protein 1 (KEAP1; Omaveloxolone), significantly modulated HCoV-229E infection, providing evidence that these compounds inhibited the virus through acting on their respective host targets. Counter-screening of all 134 primary compound candidates with SARS-CoV-2 and validation in primary cells identified Phortress, an AHR activating ligand, P-3622-targeting FDFT1, and Omaveloxolone, which activates the NFE2-like bZIP transcription factor 2 (NFE2L2) by liberating it from its endogenous inhibitor KEAP1, as antiviral candidates for both an - and a . This study provides an overview of HCoV-229E repurposing candidates and reveals novel potentially druggable viral host dependency factors hijacked by diverse coronaviruses.
Topics: Humans; Kelch-Like ECH-Associated Protein 1; Drug Repositioning; NF-E2-Related Factor 2; Coronavirus 229E, Human; Antiviral Agents; Coronavirus Infections; Thiazoles; Triterpenes
PubMed: 38319076
DOI: 10.1128/aac.01210-23 -
Science Bulletin Nov 2023Cross-species transmission of viruses from wildlife animal reservoirs, such as bats, poses a threat to human and domestic animal health. Previous studies have shown that...
Cross-species transmission of viruses from wildlife animal reservoirs, such as bats, poses a threat to human and domestic animal health. Previous studies have shown that domestic animals have important roles as intermediate hosts, enabling the transmission of genetically diverse coronaviruses from natural hosts to humans. Here, we report the identification and characterization of a novel canine coronavirus (VuCCoV), which caused an epidemic of acute diarrhea in Vulpes (foxes) in Shenyang, China. The epidemic started on November 8, 2019, and caused more than 39,600 deaths by January 1, 2022. Full-length viral genomic sequences were obtained from 15 foxes with diarrhea at the early stage of this outbreak. The VuCCoV genome shared more than 90% nucleotide identity with canine coronavirus (CCoV) for three of the four structural genes, with the S gene showing a larger amount of divergence. In addition, 67% (10/15) of the VuCCoV genomes contained an open reading frame (ORF3) gene, which was previously only detected in CCoV-I genomes. Notably, VuCCoV had only two to three amino acid differences at the partial RNA-dependent RNA polymerase (RdRp) level to bat CoV, suggesting a close genetic relationship. Therefore, these novel VuCCoV genomes represent a previously unsampled lineage of CCoVs. We also show that the VuCCoV spike protein binds to canine and fox aminopeptidase N (APN), which may allow this protein to serve as an entry receptor. In addition, cell lines were identified that are sensitive to VuCCoV using a pseudovirus system. These data highlight the importance of identifying the diversity and distribution of coronaviruses in domestic animals, which could mitigate future outbreaks that could threaten livestock, public health, and economic growth.
Topics: Animals; Dogs; Humans; Foxes; Coronavirus, Canine; Animals, Wild; SARS-CoV-2; Animals, Domestic; Disease Outbreaks; Diarrhea
PubMed: 37758615
DOI: 10.1016/j.scib.2023.09.011 -
Viruses Aug 2023(1) Background: Since the emergence of SARS-CoV-2, responsible for the COVID-19 pandemic, efforts have been made to identify antiviral compounds against human...
(1) Background: Since the emergence of SARS-CoV-2, responsible for the COVID-19 pandemic, efforts have been made to identify antiviral compounds against human coronaviruses. With the aim of increasing the diversity of molecule scaffolds, 42 natural compounds, of which 28 were isolated from lichens and 14 from their associated microorganisms (bacteria and fungi), were screened against human coronavirus HCoV-229E. (2) Methods: Antiviral assays were performed using HCoV-229E in Huh-7 and Huh-7/TMPRSS2 cells and SARS-CoV-2 in a Vero-81-derived clone with a GFP reporter probe. (3) Results: Four lichen compounds, including chloroatranol, emodin, perlatolic acid and vulpinic acid, displayed high activities against HCoV-229E (IC = 68.86, 59.25, 16.42 and 14.58 μM, respectively) and no toxicity at active concentrations. Kinetics studies were performed to determine their mode of action. The four compounds were active when added at the replication step. Due to their significant activity, they were further tested on SARS-CoV-2. Perlatolic acid was shown to be active against SARS-CoV-2. (4) Conclusions: Taken together, these results show that lichens are a source of interesting antiviral agents against human coronaviruses. Moreover, perlatolic acid might be further studied for its pan-coronavirus antiviral activity.
Topics: Humans; Lichens; Pandemics; COVID-19; SARS-CoV-2; Antiviral Agents; Coronavirus 229E, Human
PubMed: 37766264
DOI: 10.3390/v15091859 -
Frontiers in Cellular and Infection... 2023Porcine epidemic diarrhea virus (PEDV) is a member of the genera that has been associated with acute watery diarrhea and vomiting in swine. Unfortunately, no effective...
Porcine epidemic diarrhea virus (PEDV) is a member of the genera that has been associated with acute watery diarrhea and vomiting in swine. Unfortunately, no effective vaccines and antiviral drugs for PEDV are currently available. Reverse genetics systems are crucial tools for these researches. Here, a PEDV full-length cDNA clone was constructed. Furtherly, three PEDV reporter virus plasmids containing red fluorescent protein (RFP), Nano luciferase (Nluc), or green fluorescence protein (GFP) were generated using Red recombination with the GS1783 strain. These reporter-expressing recombinant (r) PEDVs showed similar growth properties to the rPEDV, and the foreign genes were stable to culture up to P9 in Vero cells. Using the Nluc-expressing rPEDV, the replication of PEDV was easily quantified, and a platform for rapid anti-PEDV drug screening was constructed. Among the three drugs, Bergenin, Umifenovir hydrochloride (Arbidol), and triterpenoids (GLTs), we found that GLTs inhibited PEDV replication mainly after the stage of virus "Entry". Overall, this study will broaden insight into the method for manipulating the PEDV genome and provide a powerful tool for screening anti-PEDV agents.
Topics: Chlorocebus aethiops; Animals; Swine; Porcine epidemic diarrhea virus; Vero Cells; Coronavirus Infections; Escherichia coli; Recombination, Genetic; Swine Diseases; Diarrhea
PubMed: 38317792
DOI: 10.3389/fcimb.2023.1338740 -
The Journal of Biological Chemistry Apr 2024Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric pathogen of the coronavirus family and caused severe economic losses to the global swine industry....
Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric pathogen of the coronavirus family and caused severe economic losses to the global swine industry. Previous studies have established that p53 is a host restriction factor for PEDV infection, and p53 degradation occurs in PEDV-infected cells. However, the underlying molecular mechanisms through which PEDV viral proteins regulate p53 degradation remain unclear. In this study, we found that PEDV infection or expression of the nucleocapsid protein downregulates p53 through a post-translational mechanism: increasing the ubiquitination of p53 and preventing its nuclear translocation. We also show that the PEDV N protein functions by recruiting the E3 ubiquitin ligase COP1 and suppressing COP1 self-ubiquitination and protein degradation, thereby augmenting COP1-mediated degradation of p53. Additionally, COP1 knockdown compromises N-mediated p53 degradation. Functional mapping using truncation analysis showed that the N-terminal domains of N protein were responsible for interacting with COP1 and critical for COP1 stability and p53 degradation. The results presented here suggest the COP1-dependent mechanism for PEDV N protein to abolish p53 activity. This study significantly increases our understanding of PEDV in antagonizing the host antiviral factor p53 and will help initiate novel antiviral strategies against PEDV.
Topics: Ubiquitin-Protein Ligases; Tumor Suppressor Protein p53; Porcine epidemic diarrhea virus; Animals; Humans; Ubiquitination; Nucleocapsid Proteins; Proteolysis; Proteasome Endopeptidase Complex; Coronavirus Infections; Chlorocebus aethiops; HEK293 Cells; Swine; Vero Cells
PubMed: 38447796
DOI: 10.1016/j.jbc.2024.107135 -
Antiviral Research Mar 2024Feline coronavirus (FCoV) is an unsegmented, single-stranded RNA virus belonging to the Alphacoronavirus genus. It can cause fatal feline infectious peritonitis (FIP) in...
Feline coronavirus (FCoV) is an unsegmented, single-stranded RNA virus belonging to the Alphacoronavirus genus. It can cause fatal feline infectious peritonitis (FIP) in cats of any ages. Currently, there are no effective prevention and control measures to against FCoV. In this study, we developed a recombinant adenovirus vaccine, AD5-N, based on the nucleocapsid(N) protein of FCoV. The immunogenicity of AD5-N was evaluated through intramuscular immunization in 6-week-old Balb/c mice and 9-12 months old cats. Compared to the control group, AD5-N specifically induced a significant increase in IgG and SIgA levels in the vaccinated mice. Furthermore, AD5-N not only effectively promoted strong cellular immune responses in cats but also induced high levels of specific SIgA, effectively helping cats resist FCoV infection. Our findings suggest that adenovirus vector vaccines based on the N gene have the potential to become candidate vaccines for the prevention and control of FCoV infection.
Topics: Cats; Animals; Mice; Adenovirus Vaccines; Adenoviridae; Coronavirus, Feline; Adenoviridae Infections; Vaccines; Coronavirus Infections; Immunoglobulin A, Secretory; Mice, Inbred BALB C; Immunity
PubMed: 38311297
DOI: 10.1016/j.antiviral.2024.105825 -
Microbial Pathogenesis Oct 2023Transmissible gastroenteritis virus (TGEV), which belongs to the coronaviruses (CoVs), causes diarrhea and high mortality rates in piglets and poses a huge threat and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Transmissible gastroenteritis virus (TGEV), which belongs to the coronaviruses (CoVs), causes diarrhea and high mortality rates in piglets and poses a huge threat and loss to the pig industry in China.
METHOD
We estimated the prevalence of TGEV in Chinese pig animals from 1983 to 2022 by screening 36 papers on TGEV investigations in China from databases such as China Knowledge Network (CNKI), Wanfang Database, Science and Technology Journal Repository (VIP), PubMed, and ScienceDirect, excluding duplicate literature and other host studies according to the exclusion criteria we developed, and excluding literature with incomplete data to extract information from studies that could estimate the prevalence of TGEV infection in pigs in mainland China.
RESULTS
A total of 36 studies (including data from 50,403 pigs) met our evaluation criteria. The overall estimated prevalence of TGEV infection in pigs in China is 10% (3887/50403), and the prevalence of TGEV in northeast China is 38% (2582/3078700) is significantly higher than the rest of China. The prevalence of TGEV infection was related to the sampling season and region.
CONCLUSION
The results of the study show that the prevalence of TGEV is clearly seasonal and regional. Therefore, further research and monitoring of the prevalence of TGEV infection and the development of control programs based on different conditions are essential. In addition, effective and robust regulatory measures should be taken in colder regions to prevent the spread and transmission of TGEV in pigs.
Topics: Animals; China; Diarrhea; Gastroenteritis; Prevalence; Swine; Transmissible gastroenteritis virus; Gastroenteritis, Transmissible, of Swine
PubMed: 37625663
DOI: 10.1016/j.micpath.2023.106320