scholarly journals Hypericin Inhibit Alpha-Coronavirus Replication by Targeting 3CL Protease

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1825
Author(s):  
Yue Zhang ◽  
Huijie Chen ◽  
Mengmeng Zou ◽  
Rick Oerlemans ◽  
Changhao Shao ◽  
...  
Keyword(s):  
Viral Replication ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Antiviral Effect ◽  
Inhibitory Effect ◽  
Economic Losses ◽  
Transmissible Gastroenteritis Virus ◽  
Diarrhea Virus ◽  
Push Forward ◽  
Transmissible Gastroenteritis

The porcine epidemic diarrhea virus (PEDV) is an Alphacoronavirus (α-CoV) that causes high mortality in infected piglets, resulting in serious economic losses in the farming industry. Hypericin is a dianthrone compound that has been shown as an antiviral activity on several viruses. Here, we first evaluated the antiviral effect of hypericin in PEDV and found the viral replication and egression were significantly reduced with hypericin post-treatment. As hypericin has been shown in SARS-CoV-2 that it is bound to viral 3CLpro, we thus established a molecular docking between hypericin and PEDV 3CLpro using different software and found hypericin bound to 3CLpro through two pockets. These binding pockets were further verified by another docking between hypericin and PEDV 3CLpro pocket mutants, and the fluorescence resonance energy transfer (FRET) assay confirmed that hypericin inhibits the PEDV 3CLpro activity. Moreover, the alignments of α-CoV 3CLpro sequences or crystal structure revealed that the pockets mediating hypericin and PEDV 3CLpro binding were highly conserved, especially in transmissible gastroenteritis virus (TGEV). We then validated the anti-TGEV effect of hypericin through viral replication and egression. Overall, our results push forward that hypericin was for the first time shown to have an inhibitory effect on PEDV and TGEV by targeting 3CLpro, and it deserves further attention as not only a pan-anti-α-CoV compound but potentially also as a compound of other coronaviral infections.

scholarly journals Enhanced efficacy of endonuclease inhibitor baloxavir acid against orthobunyaviruses when used in combination with ribavirin

2020 ◽  
Vol 75 (11) ◽  
pp. 3189-3193
Author(s):  
Sebastiaan ter Horst ◽  
Yaiza Fernandez-Garcia ◽  
Marcella Bassetto ◽  
Stephan Günther ◽  
Andrea Brancale ◽  
...  
Keyword(s):  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Docking Simulation ◽  
Antiviral Effect ◽  
Inhibitory Effect ◽  
Surface Model ◽  
La Crosse Virus ◽  
Endonuclease Domain ◽  
Substrate Cleavage

Abstract Objectives Baloxavir acid is an endonuclease inhibitor approved for use against influenza. We evaluated whether this compound also targets the endonuclease domain of orthobunyaviruses and therefore could potentially be used against orthobunyavirus infections. Methods We performed a thermal shift assay and a fluorescence resonance energy transfer (FRET)-based nuclease monitoring assay using the La Crosse virus (LACV) endonuclease and baloxavir acid to prove their interaction and identify an inhibitory effect. Their interaction was further studied in a docking simulation using Glide SP. We show that baloxavir acid inhibits the viral replication of Bunyamwera virus (BUNV)–mCherry in vitro using high-content imaging and virus yield assay. Lastly, we investigated the use of baloxavir acid in combination with ribavirin in vitro by implementing the Zero Interaction Potency response surface model. Results We show that baloxavir acid augments LACV enzyme’s melting temperature with ΔTm 9.5 ± 0.4°C and inhibited substrate cleavage with IC50 0.39 ± 0.03 μM. Moreover, our docking simulation suggests that baloxavir acid is able to establish an efficient binding with the LACV endonuclease. In the cell-based assay, we observed that baloxavir acid and ribavirin inhibited BUNV–mCherry with an EC50 of 0.7 ± 0.2 μM and 26.6 ± 8.9 μM, respectively. When used in combination, we found a maximum synergistic effect of 8.64. Conclusions The influenza endonuclease inhibitor baloxavir acid is able to bind to and interfere with the endonuclease domain of orthobunyaviruses and yields a more potent antiviral effect than ribavirin against BUNV–mCherry. The combination of both compounds results in a more potent antiviral effect, suggesting that these molecules could potentially be combined to treat orthobunyavirus-infected patients.

scholarly journals Inhibition of Porcine Epidemic Diarrhea Virus Replication and Viral 3C-Like Protease by Quercetin

2020 ◽  
Vol 21 (21) ◽  
pp. 8095
Author(s):  
Zhonghua Li ◽  
Hua Cao ◽  
Yufang Cheng ◽  
Xiaoqian Zhang ◽  
Wei Zeng ◽  
...  
Keyword(s):  
Porcine Epidemic Diarrhea Virus ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Docking Study ◽  
Binding Pocket ◽  
Inhibitory Effect ◽  
Molecular Docking Study ◽  
Replication Process ◽  
Diarrhea Virus ◽  
Porcine Epidemic Diarrhea

For the last decade, porcine epidemic diarrhea virus (PEDV) variant strains have caused severe damage to the global pig industry. Until now, no effective antivirals have been developed for the therapeutic treatment of PEDV infection. In the present study, we found that quercetin significantly suppressed PEDV infection at noncytotoxic concentrations. A molecular docking study indicated that quercetin might bind the active site and binding pocket of PEDV 3C-like protease (3CLpro). Surface plasmon resonance (SPR) analysis revealed that quercetin exhibited a binding affinity to PEDV 3CLpro. Based on the results of the fluorescence resonance energy transfer (FRET) assay, quercetin was proven to exert an inhibitory effect on PEDV 3CLpro. Since coronavirus 3CLpro is an important drug target and participates in the viral replication process, quercetin should be developed as a novel drug in the control of PEDV infection.

A portable, 3D printed, microfluidic device for multiplexed, real time, molecular detection of the porcine epidemic diarrhea virus, transmissible gastroenteritis virus, and porcine deltacoronavirus at the point of need

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Mohamed El-Tholoth ◽  
Huiwen Bai ◽  
Michael G. Mauk ◽  
Linda Saif ◽  
Haim H. Bau
Keyword(s):  
Porcine Epidemic Diarrhea Virus ◽  
Molecular Detection ◽  
Economic Losses ◽  
Transmissible Gastroenteritis Virus ◽  
Diarrhea Virus ◽  
Neonatal Pigs ◽  
Gastroenteritis Virus ◽  
3D Printed ◽  
Porcine Epidemic Diarrhea ◽  
Transmissible Gastroenteritis

The porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine deltacoronavirus (PDCoV) are coronaviruses (CoVs) of neonatal pigs that cause great economic losses to pig farms and pork processors.

scholarly journals Data standardization implementation and applications within and among diagnostic laboratories: integrating and monitoring enteric coronaviruses

2021 ◽  
pp. 104063872110021
Author(s):  
Giovani Trevisan ◽  
Leticia C. M. Linhares ◽  
Kent J. Schwartz ◽  
Eric R. Burrough ◽  
Edison de S. Magalhães ◽  
...  
Keyword(s):  
Seasonal Pattern ◽  
Laboratory Data ◽  
Information Management System ◽  
Transmissible Gastroenteritis Virus ◽  
Test Results ◽  
Diarrhea Virus ◽  
Oral Fluids ◽  
Transmissible Gastroenteritis ◽  
Technology Processes ◽  
Laboratory Information Management

Every day, thousands of samples from diverse populations of animals are submitted to veterinary diagnostic laboratories (VDLs) for testing. Each VDL has its own laboratory information management system (LIMS), with processes and procedures to capture submission information, perform laboratory tests, define the boundaries of test results (i.e., positive or negative), and report results, in addition to internal business and accounting applications. Enormous quantities of data are accumulated and stored within VDL LIMSs. There is a need for platforms that allow VDLs to exchange and share portions of laboratory data using standardized, reliable, and sustainable information technology processes. Here we report concepts and applications for standardization and aggregation of data from swine submissions to multiple VDLs to detect and monitor porcine enteric coronaviruses by RT-PCR. Oral fluids, feces, and fecal swabs were the specimens submitted most frequently for enteric coronavirus testing. Statistical algorithms were used successfully to scan and monitor the overall and state-specific percentage of positive submissions. Major findings revealed a consistently recurrent seasonal pattern, with the highest percentage of positive submissions detected during December–February for porcine epidemic diarrhea virus, porcine deltacoronavirus, and transmissible gastroenteritis virus (TGEV). After 2014, very few submissions tested positive for TGEV. Monitoring VDL data proactively has the potential to signal and alert stakeholders early of significant changes from expected detection. We demonstrate the importance of, and applications for, data organized and aggregated by using LOINC and SNOMED CTs, as well as the use of customized messaging to allow inter-VDL exchange of information.

scholarly journals Diarrhea caused by rotavirus A, B, and C in suckling piglets from southern Brazil: molecular detection and histologic and immunohistochemical characterization

2018 ◽  
Vol 30 (3) ◽  
pp. 370-376 ◽  
Author(s):  
Paula R. Almeida ◽  
Elis Lorenzetti ◽  
Raquel S. Cruz ◽  
Tatiane T. Watanabe ◽  
Priscila Zlotowski ◽  
...  
Keyword(s):  
Virus Detection ◽  
Enteric Virus ◽  
Transmissible Gastroenteritis Virus ◽  
Southern Brazil ◽  
Rt Pcr ◽  
Viral Pathogen ◽  
Rotavirus A ◽  
Diarrhea Virus ◽  
Suckling Piglets ◽  
Transmissible Gastroenteritis

Rotavirus (RV) is an important viral pathogen causing diarrhea in piglets and other mammals worldwide. We describe 34 cases from 4 diarrheal outbreaks caused by RV in unvaccinated farrowing units in southern Brazil from 2011 to 2013. We performed autopsy, histologic examinations, bacterial culture, RV immunohistochemistry (IHC), and enteric virus detection through molecular assays for rotavirus A, B, and C, transmissible gastroenteritis virus, porcine epidemic diarrhea virus, sapovirus, norovirus, and kobuvirus. Histologically, villus atrophy (29 of 34) and epithelial vacuolation (27 of 34) occurred in all 4 outbreaks. Cell debris in the lamina propria occurred in 20 cases, mostly from outbreaks A (8 of 11), C (4 of 6), and D (7 of 11). IHC was positive for RV in 21 of 34 samples. RT-PCR was positive for RV in 20 of 30 samples; RV-C was the most frequently detected RV ( n = 17). Kobuvirus was detected in 11 samples, and, in 3 of them, there was single detection of this enteric virus.

scholarly journals The Roles of Apoptosis in Swine Response to Viral Infection and Pathogenesis of Swine Enteropathogenic Coronaviruses

2020 ◽  
Vol 7 ◽  
Author(s):  
Zhichao Xu ◽  
Yun Zhang ◽  
Yongchang Cao
Keyword(s):  
Viral Infections ◽  
System Development ◽  
Biological Evolution ◽  
Host Responses ◽  
Economic Losses ◽  
Transmissible Gastroenteritis Virus ◽  
Swine Industry ◽  
Animal Virus ◽  
Diarrhea Virus ◽  
Severe Diarrhea

Apoptosis is a tightly regulated mechanism of cell death that plays important roles in various biological processes including biological evolution, multiple system development, anticancer, and viral infections. Swine enteropathogenic coronaviruses invade and damage villous epithelial cells of the small intestine causing severe diarrhea with high mortality rate in suckling piglets. Transmissible gastroenteritis virus (TGEV), Porcine epidemic diarrhea virus (PEDV), Porcine deltacoronavirus (PDCoV), and Swine acute diarrhea syndrome coronavirus (SADS-CoV) are on the top list of commonly-seen swine coronaviruses with a feature of diarrhea, resulting in significant economic losses to the swine industry worldwide. Apoptosis has been shown to be involved in the pathogenesis process of animal virus infectious diseases. Understanding the roles of apoptosis in host responses against swine enteropathogenic coronaviruses infection contribute to disease prevention and control. Here we summarize the recent findings that focus on the apoptosis during swine coronaviruses infection, in particular, TGEV, PEDV, PDCoV, and SADS-CoV.

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