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Viruses
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Animal Coronaviruses: Infection, Prevention, and Antivirals
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Animal Coronaviruses: Infection, Prevention, and Antivirals

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (20 May 2024) | Viewed by 27355

Special Issue Editor

Prof. Dr. Tomomi Takano

E-Mail Website
Guest Editor
Veterinary Infectious Disease, School of Veterinary Medicine, Kitasato University, Towada 034-8628, Japan
Interests: coronavirus; norovirus; viral gastroenteritis; antiviral drug; vaccine development; antibody-dependent enhancement; viral infection of cats and dogs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, various antiviral drugs and vaccines have been developed to combat COVID-19. Some of them have shown significant efficacy. However, given the concern about new coronavirus outbreaks in the future, more efficient antiviral drugs and vaccines are still desired.

Our understanding of coronavirus infections in animals will have good suggestions for the development of universal antiviral drugs and vaccines against all SARS-CoV-2 variants. This will also lead to strategies to combat emerging coronavirus infections in humans.

In this Special Issue, we call for a broad range of research on the pathogenesis, prevention, and antivirals of coronavirus infections in animals. We welcome research submissions on basic analyses of coronaviruses in animals (e.g., mechanisms of viral infection, infectious immunity, etc.). We also look forward to receiving contributions on studies using animal models of human coronavirus infections.

Prof. Dr. Tomomi Takano
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • animal coronavirus
  • broad-spectrum antiviral drugs
  • universal vaccine
  • oligonucleotide therapeutics
  • molecularly-targeted therapy

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Published Papers (7 papers)

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Research

13 pages, 1085 KiB  
Article
Protoporphyrin IX-Dependent Antiviral Effects of 5-Aminolevulinic Acid against Feline Coronavirus Type II
by Tomoyoshi Doki, Junna Shimada, Misa Tokunaga, Kaito To, Koichi Orino and Tomomi Takano
Viruses 2024, 16(10), 1595; https://doi.org/10.3390/v16101595 - 11 Oct 2024
Viewed by 757
Abstract
5-Aminolevulinic acid (5-ALA), a non-proteinogenic amino acid, is an intermediate in the biosynthesis of heme and exerts antiviral effects against feline coronavirus (FCoV); however, the underlying mechanisms remain unclear. In the biosynthesis of heme, 5-ALA is condensed and converted to protoporphyrin IX (PpIX), [...] Read more.
5-Aminolevulinic acid (5-ALA), a non-proteinogenic amino acid, is an intermediate in the biosynthesis of heme and exerts antiviral effects against feline coronavirus (FCoV); however, the underlying mechanisms remain unclear. In the biosynthesis of heme, 5-ALA is condensed and converted to protoporphyrin IX (PpIX), which is then transformed into heme by the insertion of ferrous iron. Previous research has suggested that the metabolites generated during heme biosynthesis contribute to the antiviral effects of 5-ALA. Therefore, the present study investigated the in vitro mechanisms responsible for the antiviral effects of 5-ALA. The results obtained revealed that 5-ALA and PpIX both effectively reduced the viral titer in the supernatant of FCoV-infected fcwf-4 cells. Moreover, PpIX exerted virucidal effects against FCoV. We also confirmed that 5-ALA increased PpIX levels in cells. While hemin induced heme oxygenase-1 gene expression, it did not reduce the viral titer in the supernatant. Sodium ferrous citrate decreased PpIX levels and suppressed the antiviral effects of 5-ALA. Collectively, these results suggest that the antiviral effects of 5-ALA against FCoV are dependent on PpIX. Full article
(This article belongs to the Special Issue Animal Coronaviruses: Infection, Prevention, and Antivirals)
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25 pages, 21769 KiB  
Article
Photodynamic Inactivation of Bovine Coronavirus with the Photosensitizer Toluidine Blue O
by Maya Margaritova Zaharieva, Pelagia Foka, Eirini Karamichali, Alexander Dimitrov Kroumov, Stanislav Philipov, Yana Ilieva, Tanya Chan Kim, Petar Podlesniy, Yordan Manasiev, Vesselin Kussovski, Urania Georgopoulou and Hristo Miladinov Najdenski
Viruses 2024, 16(1), 48; https://doi.org/10.3390/v16010048 - 27 Dec 2023
Viewed by 1609
Abstract
Coronaviruses (CoVs) belong to the group of enveloped positive-sense single-strand RNA viruses and are causative agents of respiratory, gastro-intestinal, and central nervous systems diseases in many host species, i.e., birds, mammals, and humans. Beta-CoVs revealed a great potential to cross the barrier between [...] Read more.
Coronaviruses (CoVs) belong to the group of enveloped positive-sense single-strand RNA viruses and are causative agents of respiratory, gastro-intestinal, and central nervous systems diseases in many host species, i.e., birds, mammals, and humans. Beta-CoVs revealed a great potential to cross the barrier between species by causing three epidemics/pandemics among humans in the 21st century. Considering the urgent need for powerful antiviral agents for decontamination, prevention, and treatment of BCoV infections, we turned our attention to the possibility of photodynamic inactivation with photosensitizers in combination with light irradiation. In the present study, we evaluated, for the first time, the antiviral activity of toluidine blue O (TBO) against Beta-coronavirus 1 (BCoV) in comparison to methylene blue (MB). First, we determined the in vitro cytotoxicity of MB and TBO on the Madin–Darby bovine kidney (MDBK) cell line with ISO10993-5/Annex C. Thereafter, BCoV was propagated in MDBK cells, and the virus titer was measured with digital droplet PCR, TCID50 assay and plaque assay. The antiviral activity of non-toxic concentrations of TBO was estimated using the direct inactivation approach. All effects were calculated in MAPLE 15® mathematical software by developing programs for non-linear modeling and response surface analysis. The median inhibitory concentration (IC50) of TBO after 72 h of incubation in MDBK cells was 0.85 µM. The antiviral activity of TBO after the direct inactivation of BCoV (MOI = 1) was significantly stronger than that of MB. The median effective concentration (EC50) of TBO was 0.005 µM. The cytopathic effect decreased in a concentration-dependent manner, from 0.0025 to 0.01 µM, and disappeared fully at concentrations between 0.02 and 0.3 µM of TBO. The number of virus particles also decreased, depending on the concentration applied, as proven by ddPCR analysis. In conclusion, TBO exhibits significant potential for direct inactivation of BCoV in vitro, with a very high selectivity index, and should be subjected to further investigation, aiming at its application in veterinary and/or human medical practice. Full article
(This article belongs to the Special Issue Animal Coronaviruses: Infection, Prevention, and Antivirals)
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11 pages, 936 KiB  
Article
Chitinase-1 Activity in Serum of Cats with FIP
by Angelica Stranieri, Gabriela Ávila Morales, Laura Brusasco and Saverio Paltrinieri
Viruses 2023, 15(9), 1815; https://doi.org/10.3390/v15091815 - 25 Aug 2023
Viewed by 1121
Abstract
Background: Chitotriosidase (chitinase 1 or CHIT1) is secreted by activated macrophages. Macrophages are involved in the pathogenesis of feline infectious peritonitis (FIP). No reports on CHIT1 activity in cats with FIP are available. Objective: To preliminarily investigate the possible changes in serum CHIT1 [...] Read more.
Background: Chitotriosidase (chitinase 1 or CHIT1) is secreted by activated macrophages. Macrophages are involved in the pathogenesis of feline infectious peritonitis (FIP). No reports on CHIT1 activity in cats with FIP are available. Objective: To preliminarily investigate the possible changes in serum CHIT1 activity in cats with FIP. Methods: CHIT1 activity was measured in serum samples from clinically healthy cats (n = 17), cats with FIP (n = 19) and cats with diseases potentially characterized by macrophage activation (n = 20), after a preliminary assessment of the imprecision and linearity of the method. Results: The highest CHIT1 activity was found in cats with FIP, followed by sick cats and clinically healthy cats. The magnitude of the differences between groups was higher than the intra- and inter-assay imprecision of the method (<5% and >57%, respectively). Based on receiver operating characteristic (ROC) curves, CHIT1 may differentiate sick from clinically healthy cats and, to a lesser extent, cats with FIP from cats without FIP. Conclusions: CHIT1 activity may identify sick cats and, within the appropriate clinical context, cats with FIP, although larger and more standardized studies, coupled with additional information on analytical performances of the method, are required to fully explore the diagnostic or prognostic potential of this test for FIP. Full article
(This article belongs to the Special Issue Animal Coronaviruses: Infection, Prevention, and Antivirals)
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15 pages, 5253 KiB  
Article
Efficacy of Oral Remdesivir Compared to GS-441524 for Treatment of Cats with Naturally Occurring Effusive Feline Infectious Peritonitis: A Blinded, Non-Inferiority Study
by Emma Cosaro, Jully Pires, Diego Castillo, Brian G. Murphy and Krystle L. Reagan
Viruses 2023, 15(8), 1680; https://doi.org/10.3390/v15081680 - 1 Aug 2023
Cited by 7 | Viewed by 7987
Abstract
Nucleoside analogs GS-441524 and remdesivir (GS-5734) are effective in treating cats with feline infectious peritonitis (FIP). However, no studies have compared the efficacy between antiviral medications. The objective of this study was to evaluate the efficacy of orally administered GS-442514 (12.5–15 mg/kg) compared [...] Read more.
Nucleoside analogs GS-441524 and remdesivir (GS-5734) are effective in treating cats with feline infectious peritonitis (FIP). However, no studies have compared the efficacy between antiviral medications. The objective of this study was to evaluate the efficacy of orally administered GS-442514 (12.5–15 mg/kg) compared to orally administered remdesivir (25–30 mg/kg) in a double-blinded non-inferiority trial. Eighteen cats with effusive FIP were prospectively enrolled and randomly assigned to receive either GS-442514 or remdesivir. Cats were treated daily for 12 weeks and evaluated at week 0, 12, and 16. Survival and disease remission at week 16 were compared between groups. Five of 9 (55%) cats treated GS-441524 and 7/9 (77%) cats treated with remdesivir survived, with no difference in survival rate (p = 0.2). Remdesivir fulfilled the criteria for non-inferiority with a difference in survival of 22% (90% CI; −13.5–57.5%). Three of the 18 cats died within 48 h of enrollment. Excluding these cats, 5/6 (83%) of the cats treated with GS-441524 and 7/9 (77%) of the cats treated with remdesivir survived. These findings suggest that both orally administered GS-441524 and remdesivir are safe and effective anti-viral medications for the treatment of effusive FIP. Further optimization of the first 48 h of treatment is needed. Full article
(This article belongs to the Special Issue Animal Coronaviruses: Infection, Prevention, and Antivirals)
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14 pages, 267 KiB  
Article
Stopping Feline Coronavirus Shedding Prevented Feline Infectious Peritonitis
by Diane D. Addie, Flora Bellini, Johanna Covell-Ritchie, Ben Crowe, Sheryl Curran, Mark Fosbery, Stuart Hills, Eric Johnson, Carrie Johnson, Steven Lloyd and Oswald Jarrett
Viruses 2023, 15(4), 818; https://doi.org/10.3390/v15040818 - 23 Mar 2023
Cited by 3 | Viewed by 9640
Abstract
After an incubation period of weeks to months, up to 14% of cats infected with feline coronavirus (FCoV) develop feline infectious peritonitis (FIP): a potentially lethal pyogranulomatous perivasculitis. The aim of this study was to find out if stopping FCoV faecal shedding with [...] Read more.
After an incubation period of weeks to months, up to 14% of cats infected with feline coronavirus (FCoV) develop feline infectious peritonitis (FIP): a potentially lethal pyogranulomatous perivasculitis. The aim of this study was to find out if stopping FCoV faecal shedding with antivirals prevents FIP. Guardians of cats from which FCoV had been eliminated at least 6 months earlier were contacted to find out the outcome of their cats; 27 households were identified containing 147 cats. Thirteen cats were treated for FIP, 109 cats shed FCoV and 25 did not; a 4–7-day course of oral GS-441524 antiviral stopped faecal FCoV shedding. Follow-up was from 6 months to 3.5 years; 11 of 147 cats died, but none developed FIP. A previous field study of 820 FCoV-exposed cats was used as a retrospective control group; 37 of 820 cats developed FIP. The difference was statistically highly significant (p = 0.0062). Cats from eight households recovered from chronic FCoV enteropathy. Conclusions: the early treatment of FCoV-infected cats with oral antivirals prevented FIP. Nevertheless, should FCoV be re-introduced into a household, then FIP can result. Further work is required to establish the role of FCoV in the aetiology of feline inflammatory bowel disease. Full article
(This article belongs to the Special Issue Animal Coronaviruses: Infection, Prevention, and Antivirals)
19 pages, 2532 KiB  
Article
Development of an IgY-Based Treatment to Control Bovine Coronavirus Diarrhea in Dairy Calves
by Marina Bok, Celina G. Vega, Matias Castells, Rodney Colina, Andrés Wigdorovitz and Viviana Parreño
Viruses 2023, 15(3), 708; https://doi.org/10.3390/v15030708 - 9 Mar 2023
Cited by 1 | Viewed by 2860
Abstract
Bovine Coronavirus (BCoV) is a major pathogen associated with neonatal calf diarrhea. Standard practice dictates that to prevent BCoV diarrhea, dams should be immunized in the last stage of pregnancy to increase BCoV-specific antibody (Ab) titers in serum and colostrum. For the prevention [...] Read more.
Bovine Coronavirus (BCoV) is a major pathogen associated with neonatal calf diarrhea. Standard practice dictates that to prevent BCoV diarrhea, dams should be immunized in the last stage of pregnancy to increase BCoV-specific antibody (Ab) titers in serum and colostrum. For the prevention to be effective, calves need to suck maternal colostrum within the first six to twelve hours of life before gut closure to ensure a good level of passive immunity. The high rate of maternal Ab transfer failure resulting from this process posed the need to develop alternative local passive immunity strategies to strengthen the prevention and treatment of BCoV diarrhea. Immunoglobulin Y technology represents a promising tool to address this gap. In this study, 200 laying hens were immunized with BCoV to obtain spray-dried egg powder enriched in specific IgY Abs to BCoV on a large production scale. To ensure batch-to-batch product consistency, a potency assay was statistically validated. With a sample size of 241, the BCoV-specific IgY ELISA showed a sensitivity and specificity of 97.7% and 98.2%, respectively. ELISA IgY Abs to BCoV correlated with virus-neutralizing Ab titers (Pearson correlation, R2 = 0.92, p < 0.001). Most importantly, a pilot efficacy study in newborn calves showed a significant delay and shorter duration of BCoV-associated diarrhea and shedding in IgY-treated colostrum-deprived calves. Calves were treated with milk supplemented with egg powder (final IgY Ab titer to BCoV ELISA = 512; VN = 32) for 14 days as a passive treatment before a challenge with BCoV and were compared to calves fed milk with no supplementation. This is the first study with proof of efficacy of a product based on egg powder manufactured at a scale that successfully prevents BCoV-associated neonatal calf diarrhea. Full article
(This article belongs to the Special Issue Animal Coronaviruses: Infection, Prevention, and Antivirals)
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10 pages, 2252 KiB  
Communication
Small-Molecule RAF265 as an Antiviral Therapy Acts against PEDV Infection
by Jing Wang, Wen-Jun Tian, Cui-Cui Li, Xiu-Zhong Zhang, Kai Fan, Song-Li Li and Xiao-Jia Wang
Viruses 2022, 14(10), 2261; https://doi.org/10.3390/v14102261 - 15 Oct 2022
Cited by 2 | Viewed by 2151
Abstract
Porcine epidemic diarrhea virus (PEDV), a member of the family Coronaviridae, causes acute diarrhea, vomiting, dehydration, and high mortality in newborn piglets, and has caused significant economic losses in the pig industry. There are currently no specific drugs available to treat PEDV. [...] Read more.
Porcine epidemic diarrhea virus (PEDV), a member of the family Coronaviridae, causes acute diarrhea, vomiting, dehydration, and high mortality in newborn piglets, and has caused significant economic losses in the pig industry. There are currently no specific drugs available to treat PEDV. Viruses depend exclusively on the cellular machinery to ensure an efficient replication cycle. In the present study, we found that small-molecule RAF265, an anticancer drug that has been shown to be a potent inhibitor of RAF, reduced viral loads of PEDV by 4 orders of magnitude in Vero cells, and protected piglets from virus challenge. RAF265 reduced PEDV production by mediating cytoskeleton arrangement and targeting the host cell’s translation machinery. Treatment with RAF265 inhibited viral entry of PEDV S-glycoprotein pseudotyped viral vector particle (PEDV-pp), at half maximal effective concentrations (EC50) of 79.1 nM. RAF265 also presented potent inhibitory activity against viral infection by SARS-CoV-2-pp and SARS-CoV-pp. The present work may provide a starting point for further progress toward the development of antiviral strategies effective against coronavirus PEDV. Full article
(This article belongs to the Special Issue Animal Coronaviruses: Infection, Prevention, and Antivirals)
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