Transmissible Gastroenteritis Research Articles

Bioinformatic Analysis of Differentially Expressed Genes in Porcine Intestinal Epithelial Cells Infected with Transmissible Gastroenteritis Virus

Bioinformatic Analysis of Differentially Expressed Genes in Porcine Intestinal Epithelial Cells Infected with Transmissible Gastroenteritis Virus

A Plasma-Generating N-95 Respirator Decontamination Unit Created from a Microwave Oven

Wearing a mask population-wide is an important preventive measure in addressing COVID-19 and potential future pandemics. We showed how a household microwave oven, a coat-hanger, and a coffee cup can generate plasma that can be used to decontaminate N95 respirators in less than 1 minute. We proved that microwave-generated plasma can reduce infectivity of the Tulane virus and the transmissible gastroenteritis virus (TGEV) on N95 respirators by > 3-log<sub>10</sub>. We further studied the Tulane virus by molecular assays to understand inactivation mechanisms, and we found that the plasma damages both viral proteins and genomes. Spectroscopy of the plasma revealed OH and C-containing radicals as the most prevalent active species expected to cause virus inactivation. The respirators still maintained filtration and fit even after 10 cycles of the plasma treatment. We believe that microwave-generated plasma is an easily accessible respirator decontamination technique that everyone could use for safe respirator reuse.

Anticoronavirus Activity of Water-Soluble Pristine C60 Fullerenes: In Vitro and In Silico Screenings.

The emergence of a new member of the Coronaviridae family, which caused the 2020 pandemic, requires detailed research on the evolution of coronaviruses, their structure and properties, and interaction with cells. Modern nanobiotechnologies can address the many clinical challenges posed by the COVID-19 pandemic. In particular, they offer new therapeutic approaches using biocompatible nanostructures with "specific" antiviral activity. Therefore, the nanosized spherical-like molecule (0.72 nm in diameter) composed of 60 carbon atoms, C60 fullerene, is of interest in terms of fighting coronaviruses due to its high biological activity. In here, we aim to evaluate the effectiveness of anticoronavirus action of water-soluble pristine C60 fullerene in the model and in vitro systems. As a model, apathogenic for human coronavirus, we used transmissible gastroenteritis virus of swine (TGEV), which we adapted to the BHK-21 cell culture (kidney cells of a newborn Syrian hamster). The shape and size of the particles present in C60 fullerene aqueous colloidal solution (C60FAS) of given concentration, as well as C60FAS stability (value of zeta potential) were studied using microscopic (STM, scanning tunneling microscopy, and AFM, atomic force microscopy) and spectroscopic (DLS, dynamic light scattering) methods. The cytopathic effect of TGEV was determined with the help of a Leica DM 750 microscope and the degree of monolayer changes in cells was assessed. The microscopy of the viral suspension was performed using a high resolution transmission electron microscope (HRTEM; JEM-1230, Japan). Finally, the search for and design of optimal possible complexes between C60 fullerene and target proteins in the structure of SARS-CoV-2 coronavirus, evaluation of their stability in the simulated cellular environment were performed using molecular dynamics and docking methods. It was found that the maximum allowable cytotoxic concentration of C60 fullerene is 37.5±3.0μg/ml. The investigated C60FAS reduces the titer of coronavirus infectious activity by the value of 2.00±0.08TCID50/ml. It was shown that C60 fullerene interacts directly with SARS-CoV-2 proteins, such as RdRp (RNA-dependent RNA polymerase) and 3CLpro (3-chymotrypsin-like protease), which is critical for the life cycle of the coronavirus and, thus, inhibits its functional activity. In both cases, C60 fullerene fills the binding pocket and gets stuck there through stacking and steric interactions. Pioneer in vitro study to identify the anticoronavirus activity of water-soluble pristine C60 fullerenes indicates that they are highly promising for further preclinical studies, since a significant inhibition of the infectious activity of swine coronavirus of transmissible gastroenteritis in BHK-21 cell culture was found. According to molecular modeling results, it was shown that C60 fullerene can create the stable complexes with 3CLpro and RdRp proteins of SARS-CoV-2 coronavirus and, thus, suppress its functional activity.

Canine corona virus in Nigeria: a missed diagnosis or an under reported panzootics?

In Nigeria, dogs are kept as a companion animal, or a source of protein,[1], with an estimated dog population of about 2-5million based on the population density of 1;13 households,[2,3]. Canine Corona Virus,(CCoV) is a viral disease enzootic in dog worldwide,[4]. Two distinct genera are known, CCoV-I, CCoV-II, [5,6], they are responsible for mild, self-limiting gastrointestinal infections in dogs,[5]. CCoV-II has two subgenera CCoV-IIa and CCoV-IIb based on its genetic relatedness to transmissible gastroenteritis virus of Swine,(TGEV),[5]. However, in May 2005, the outbreak of a fetal, systemic disease in 3 miniature pinschers and a cocker spaniel, characterized by lethargy, vomiting, pyrexia, hematuria and neurological symptom initially taught to be caused by Parvovirus was identified as a pantropic coronavirus variant (CCoV-IIa),[5]. Curiously, CCoV is rarely reported or listed as a differential diagnosis, during clinical diagnosis and management of Canine diseases in Nigeria. Similarly, a retrospective review of the animal disease line list from the Federal department of Veterinary services in Nigeria between, 2000- 2010, showed that no case of CCoVs was reported across the 36 States of Nigeria and the Federal capital territory (FCT), neither was it listed as a reportable animal disease on the Animal disease information system server 2(ARIS 2), the official platform for reporting animal diseases in Nigeria during the period in view. Consequently, we conducted a cross-sectional survey involving 69 Veterinarian in small animal practices in Nigeria, a structured pre-tested questionnaire was purposively administered to clinicians to determine the availability of laboratory services as an integral component of Veterinary diagnostics, the basis on which management of suspected cases of CCoV, Canine Parvo viral enteritis, and Canine Adenovirus was made by a veterinarian. On the availability of laboratory services, 20(28.6%) of respondents has no laboratory facilities,(LF) as part of their clinical practice. Thirty-nine (57%) relied solely on a clinical symptom alone to make a diagnosis of Canine diseases, 3(11.4%) of Veterinary hospital,(VH) with LF conducts the virological test. Fifteen (22.9%) of clinician-reported managing suspected cases of CCoV, however, 8(54.6%) of them posited that management was based on clinical symptoms alone. We reported that only 14(20.6%) of dogs presenting symptoms similar to canine Parvo viral enteritis, Adenoviruses were screened for Canine coronavirus.

Naturally Occurring Animal Coronaviruses as Models for Studying Highly Pathogenic Human Coronaviral Disease.

Coronaviruses (CoVs) comprise a large group of positive stranded RNA viruses that infect a diverse host range including birds and mammals. Infection with CoVs typically presents as mild to severe respiratory or enteric disease, but CoVs have the potential to cause significant morbidity or mortality in highly susceptible age groups. CoVs have exhibited a penchant for jumping species barriers throughout history with devastating effects. The emergence of highly pathogenic or infectious CoVs in humans over the past 20 years, including severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and most recently severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underscores the significant threat that CoV spillovers pose to humans. Similar to the emergence of SARS-CoV-2, CoVs have been devastating to commercial animal production over the past century, including infectious bronchitis virus in poultry and bovine CoV, as well as the emergence and reemergence of multiple CoVs in swine including transmissible gastroenteritis virus, porcine epidemic diarrhea virus, and porcine deltacoronavirus. These naturally occurring animal CoV infections provide important examples for understanding CoV disease as many animal CoVs have complex pathogenesis similar to SARS-CoV-2 and can shed light on the ongoing SARS-CoV-2 outbreak. We provide an overview and update regarding selected existing animal CoVs and their primary host species, diseases caused by CoVs, how CoVs jump species, whether these CoVs pose an outbreak risk or risk to humans, and how we can mitigate these risks.

Inhibition of SARS-CoV-2 by Highly Potent Broad-Spectrum Anti-Coronaviral Tylophorine-Based Derivatives.

Tylophorine-based compounds and natural cardiotonic steroids (cardenolides and bufadienolides) are two classes of transmissible gastroenteritis coronavirus inhibitors, targeting viral RNA and host cell factors, respectively. We tested both types of compounds against two types of coronaviruses, to compare and contrast their antiviral properties, and with view to their further therapeutic development. Examples of both types of compounds potently inhibited the replication of both feline infectious peritonitis virus and human coronavirus OC43 with EC50 values of up to 8 and 16 nM, respectively. Strikingly, the tylophorine-based compounds tested inhibited viral yields of HCoV-OC43 to a much greater extent (7–8 log magnitudes of p.f.u./ml) than the cardiotonic steroids (about 2–3 log magnitudes of p.f.u./ml), as determined by end point assays. Based on these results, three tylophorine-based compounds were further examined for their anti-viral activities on two other human coronaviruses, HCoV-229E and SARS-CoV-2. These three tylophorine-based compounds inhibited HCoV-229E with EC50 values of up to 6.5 nM, inhibited viral yields of HCoV-229E by 6–7 log magnitudes of p.f.u./ml, and were also found to inhibit SARS-CoV-2 with EC50 values of up to 2.5–14 nM. In conclusion, tylophorine-based compounds are potent, broad-spectrum inhibitors of coronaviruses including SARS-CoV-2, and could be used for the treatment of COVID-19.

A LITERATURE REVIEW OF NOVEL COVID-19 AND RELATED CORONAVIRUSES OUTBREAKS IN THE 1960S UNTIL 21ST CENTURY

Coronavirus (CoVs) is a large group of viruses known to affect birds and mammals including humans. This review aims to present the types of human coronavirus and animal coronavirus studied and displaying the relationships of these coronaviruses to weather, meteorology and climatology. Human coronaviruses (HCoV) in review are namely 229E, NL63, OC43 and HKU1 and other HCoV which are Severe Acute Respiratory Syndrome (SARS-CoV), Middle East Respiratory Syndrome (MERS-CoV) and COVID-19 (SARS-CoV-2). These HcoV originated as animal infections which then develop and ultimately transmitted to humans. CoV can also be found in animals which are Canine Respiratory Coronavirus (CRCoV), Murine Coronavirus Rat Hepatitis Virus (MHV), Transmissible Gastroenteritis Virus (TGEV), Bovine Coronavirus (BCoV), Feline Coronavirus (FCoV), Canine Coronavirus (CCoV) and Turkey Coronavirus (TCV). CoV has been found to last longer in the atmosphere at lower temperatures and lower relative humidity. Thus, some coronavirus outbreaks can mostly be attributed to cold and dry climates for more effective CoV transmission. Identified CoV are mostly active when the temperature is between 9 °C and 24 °C. Findings in this review can serve as knowledge and guidance for individuals, related organizations and governments to be prepared for the CoV threats that is currently occurring and that is likely to re-emerge in the coming years. It is also intended to provide useful baseline information for policymakers and the public. KEYWORDS: climatology, coronavirus (CoVs), human coronaviruses (HCoV), meteorology, weather

LEADERSHIP EMERGENCY PREPAREDNESS IN RELATLION TO COVID-19: A CASE STUDY IN WEST POKOT COUNTY

Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds. In humans, these viruses cause respiratory tract infections that can range from mild to lethal. Mild illnesses include some cases of the common cold (which is also caused by other viruses, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS, and COVID-19. Symptoms in other species vary: in chickens, they cause an upper respiratory tract disease, while in cows and pigs they cause diarrhea. There are as yet no vaccines or antiviral drugs to prevent or treat human coronavirus infections. Coronaviruses constitute the subfamily Orthocoronavirinae, in the family Coronaviridae, order Nidovirales, and realm Riboviria. They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses ranges from approximately 26 to 32 kilobases, one of the largest among viruses. They have characteristic club-shaped spikes that project from their surface, which in electron micrographs create an image reminiscent of the solar corona, from which their name derives The name coronavirus is derived from Latin corona, meaning crown or wreath, itself a borrowing from Greek κορώνη korṓnē, garland, wreath. The name was coined by June Almeida and David Tyrrell who first observed and studied human coronaviruses. The word was first used in print in 1968 by an informal group of virologists in the journal Nature to designate the new family of viruses. The name refers to the characteristic appearance of virions (the infective form of the virus) by electron microscopy, which have a fringe of large, bulbous surface projections creating an image reminiscent of the solar corona or halo. This morphology is created by the viral spike peplomers, which are proteins on the surface of the virus. Coronaviruses were first discovered in the 1930s when an acute respiratory infection of domesticated chickens was shown to be caused by infectious bronchitis virus (IBV). Arthur Schalk and M.C. Hawn described in 1931 a new respiratory infection of chickens in North Dakota. The infection of new-born chicks was characterized by gasping and listlessness. The chicks mortality rate was 40–90%. Fred Beaudette and Charles Hudson(1998) six years later successfully isolated and cultivated the infectious bronchitis virus which caused the disease In the 1940s, two more animal coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), were isolated.[17] It was not realized at the time that these three different viruses were related. Human coronaviruses were discovered in the 1960s. They were isolated using two different methods in the United Kingdom and the United States. E.C. Kendall, Malcolm Byone, and David Tyrrell working at the Common Cold Unit of the British Medical Research Council in 1960 isolated from a boy a novel common cold virus B814 The virus was not able to be cultivated using standard techniques which had successfully cultivated rhinoviruses, adenoviruses and other known common cold viruses. In 1965, Tyrrell and Byone successfully cultivated the novel virus by serially passing it through organ culture of human embryonic trachea. The new cultivating method was introduced to the lab by Bertil Hoorn. The isolated virus when intranasally inoculated into volunteers caused a cold and was inactivated by ether which indicated it had a lipid envelope. Around the same time, Dorothy Hamre and John Procknow at the University of Chicago isolated a novel cold virus 229E from medical students, which they grew in kidney tissue culture. The novel virus 229E, like the virus strain B814, when inoculated into volunteers caused a cold and was inactivated by ether.

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

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.

Inhibitory effects of recombinant porcine interferon-α on porcine transmissible gastroenteritis virus infections in TGEV-seronegative piglets

Our previous research obtained purified recombinant porcine interferon-α (rPoIFN-α) containing thioredoxin (Trx) fusion tag in E. coli Rosetta (DE3). Here, we evaluate the efficacy of this rPoIFN-α to prevent piglets from the infection of the transmissible gastroenteritis virus (TGEV) attack. In this experiment, twenty-five TGEV-seronegative piglets were randomly divided into five groups. Group 1 was positive control and only challenged with TGEV; Pigs in groups 2–4 were pretreated with 2 × 10(7)IU/pig, 2 × 10(6)IU/pig, and 2 × 10(5)IU/pig rPoIFN-α before TGEV challenge. The fifth group is a negative control group. The animals of this group are pretreated only with Trx protein-containing PBS solution without TGEV challenge. After 48 h of rPoIFN-α pretreatment, the pigs in groups 1–4 were challenged by TGEV, and the pigs in group 5 were administered with PBS. The surveillance results show that Pigs pre-treated with 2 × 10 (7) IU/pig rPoIFN-α are fully aligned with the violent TGEV attack. Pigs pretreated with 2 × 10 (6) IU/pig rPoIFN-α are partially aligned with the violent TGEV attack. Though piglets pretreated with 2 × 10(6) IU/pig or 2 × 10(5)IU/pig rPoIFN-α cannot be adapted to the challenge of TGEV. However, the use of this dose of rPoIFN-α could put off the clinical signs of pigs than the positive control group of the above. These results indicate that rPoIFN-α can protect pigs from the infection of potential TGEV or delay the appearance of clinical symptoms, and its effect is dose-dependent.

Tomatidine inhibits porcine epidemic diarrhea virus replication by targeting 3CL protease

Porcine epidemic diarrhea virus (PEDV) causes lethal diarrhea in suckling piglets, leading to severe economic losses worldwide. There is an urgent need to find new therapeutic methods to prevent and control PEDV. Not only is there a shortage of commercial anti-PEDV drugs, but available commercial vaccines fail to protect against highly virulent PEDV variants. We screened an FDA-approved library of 911 natural products and found that tomatidine, a steroidal alkaloid extracted from the skin and leaves of tomatoes, demonstrates significant inhibition of PEDV replication in Vero and IPEC-J2 cells in vitro. Molecular docking and molecular dynamics analysis predicted interactions between tomatidine and the active pocket of PEDV 3CL protease, which were confirmed by fluorescence spectroscopy and isothermal titration calorimetry (ITC). The inhibiting effect of tomatidine on 3CL protease was determined using cleavage visualization and FRET assay. Tomatidine-mediated blocking of 3CL protease activity in PEDV-infected cells was examined by western blot detection of the viral polyprotein in PEDV-infected cells. It indicates that tomatidine inhibits PEDV replication mainly by targeting 3CL protease. In addition, tomatidine also has antiviral activity against transmissible gastroenteritis virus (TGEV), porcine reproductive and respiratory syndrome virus (PRRSV), encephalo myocarditis virus (EMCV) and seneca virus A (SVA) in vitro. These results may be helpful in developing a new prophylactic and therapeutic strategy against PEDV and other swine disease infections.

Evolution of Transmissible Gastroenteritis Virus (TGEV): A Codon Usage Perspective.

Transmissible gastroenteritis virus (TGEV) is a coronavirus associated with diarrhea and high mortality in piglets. To gain insight into the evolution and adaptation of TGEV, a comprehensive analysis of phylogeny and codon usage bias was performed. The phylogenetic analyses of maximum likelihood and Bayesian inference displayed two distinct genotypes: genotypes I and II, and genotype I was classified into subtypes Ia and Ib. The compositional properties revealed that the coding sequence contained a higher number of A/U nucleotides than G/C nucleotides, and that the synonymous codon third position was A/U-enriched. The principal component analysis based on the values of relative synonymous codon usage (RSCU) showed the genotype-specific codon usage patterns. The effective number of codons (ENC) indicated moderate codon usage bias in the TGEV genome. Dinucleotide analysis showed that CpA and UpG were over-represented and CpG was under-represented in the coding sequence of the TGEV genome. The analyses of Parity Rule 2 plot, ENC-plot, and neutrality plot displayed that natural selection was the dominant evolutionary driving force in shaping codon usage preference in genotypes Ia and II. In addition, natural selection played a major role, while mutation pressure had a minor role in driving the codon usage bias in genotype Ib. The codon adaptation index (CAI), relative codon deoptimization index (RCDI), and similarity index (SiD) analyses suggested that genotype I might be more adaptive to pigs than genotype II. Current findings contribute to understanding the evolution and adaptation of TGEV.

Assessments of different inactivating reagents in formulating transmissible gastroenteritis virus vaccine

BackgroundTransmissible gastroenteritis virus (TGEV) causes enteric infection in piglets, characterized by vomiting, severe diarrhea and dehydration, and the mortality in suckling piglets is often high up to 100%. Vaccination is an effective measure to control the disease caused by TGEV.MethodsIn this study, cell-cultured TGEV HN-2012 strain was inactivated by formaldehyde (FA), β-propiolactone (BPL) or binaryethylenimine (BEI), respectively. Then the inactivated TGEV vaccine was prepared with freund's adjuvant, and the immunization effects were evaluated in mice. The TGEV-specific IgG level was detected by ELISA. The positive rates of CD4+, CD8+, CD4+IFN-γ+, CD4+IL-4+ T lymphocytes were detected by flow cytometry assay. Lymphocyte proliferation assay and gross pathology and histopathology examination were also performed to assess the three different inactivating reagents in formulating TGEV vaccine.ResultsThe results showed that the TGEV-specific IgG level in FA group (n = 17) was earlier and stronger, while the BEI group produced much longer-term IgG level. The lymphocyte proliferation test demonstrated that the BEI group had a stronger ability to induce spleen lymphocyte proliferation. The positive rates of CD4+ and CD8+ T lymphocyte subsets of peripheral blood lymphocyte in BEI group was higher than that in FA group and BPL groups by flow cytometry assay. The positive rate of CD4+IFN-γ+ T lymphocyte subset was the highest in the BPL group, and the positive rate of CD4+IL-4+ T lymphocyte subset was the highest in the FA group. There were no obvious pathological changes in the vaccinated mice and the control group after the macroscopic and histopathological examination.ConclusionsThese results indicated that all the three experimental groups could induce cellular and humoral immunity, and the FA group had the best humoral immunity effect, while the BEI group showed its excellent cellular immunity effect.

A Focus On Coronaviruses Infections In Animals: Review Article

Coronaviruses are large, enveloped and single-stranded, non-segmented with positive sense RNA virus belong to Nidovirus, family Coronavirirdae and included two subfamilies Orthocoronavirinae and Letovirinae. There are four genera variable in antigenestic characteristic and cross-reactivity (Alpha-coronavirus, Beta-coronavirus, Gamma-coronavirus and Delta-coronavirus) affect mammals and birds while Bafinivirus affect fish and cause different diseases in the vertebrate animals and human, so this review listed most important diseases in some animals which cause economic problems as in the avian cause infectious bronchitis(IB), in the bovine cause diseases in both bowl and respiratory system, Enteric form Disease in the equine, two forms of diseases have been occurred in the feline ( feline enteric coronavirus and feline infectious peritonitis), in canine cause enteric and respiratory syndrome while in the porcine the diseases occur as are Transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine delta coronavirus (PDCoV).Also, coronaviruses affect aquatic animals and cause general clinical signs in fish. Some of these pathogens transmitted from camel and bates and causes diseases for human as SARS, MERS and SARS-2.From these review the conclusion is the hygiene practices and biosecurity are more important to prevent the emerging diseases in both human and animals cause by a coronavirus.

Rhodanine derivative LJ001 inhibits TGEV and PDCoV replication in vitro

Transmissible gastroenteritis virus (TGEV) and porcine deltacoronavirus (PDCoV) are members of the family coronaviridae and mainly cause acute diarrhea/vomiting, dehydration and mortality in piglets, which lead to huge economic losses to the swine industry. Rhodanine derivative LJ001 has been verified to be effective against some enveloped virus infections in vitro. In this study, we evaluated the antiviral activity of LJ001 towards TGEV and PDCoV replication on swine testicular(ST) cells. Our results showed the 50 % cellular cytotoxicity (CC50) value of LJ001 was 146.4 μM on ST cell. The virus titers of TGEV and PDCoV were obviously decreased in the presence of LJ001 with the concentrations of 3.125 and 12.5 μM, and LJ001 potently inhibited TGEV and PDCoV infection at the replication stages of viral life cycle. Further study indicated that LJ001 inhibited TGEV and PDCoV replication by inhibition of viral RNA and protein synthesis, and reducing virus yields at 12 and 24 h post-inoculation. These data indicated that LJ001 had antiviral activities on TGEV and PDCoV replications in vitro, which may serve as a new candidate for treatment of coronaviruses infections.

A Proposed Weapon in the Anti-COVID-19 Arsenal: Percutaneous Zinc Absorption

Coronaviruses are large, enveloped, single-stranded, positive-sense RNA viruses with a genome of approximately 30 kilobases in length. The genus Coronavirus belongs to the family Coronaviridae in the order Nidovirales. They are classified into three groups. Group 1 contains various mammalian viruses including porcine epidemic diarrhea virus, porcine transmissible gastroenteritis virus, and human coronaviruses 229E and NL63. Group 2 includes canine respiratory coronavirus among other mammalian viruses and human coronavirus OC43. Human severe acute respiratory syndrome coronavirus (SARS-CoV) is considered a distant relative of this group. Group 3 contains solely avian coronaviruses. Human coronaviruses (HCoVs) cause respiratory infections, mainly, but gastroenteritis and neurological disorders may also occur. So far, at least six human coronaviruses have been described including SARS-CoV2, which was just identified in 2020, and two of these coronaviruses (OC43 and 229E) are responsible for 10-30% of all common colds. HCoV-HKU1 is mostly associated with bronchiolitis and pneumonia.

CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance

Porcine reproductive and respiratory syndrome virus (PRRSV) and transmissible gastroenteritis virus (TGEV) are two highly infectious and lethal viruses causing major economic losses to pig production. Here, we report generation of double-gene-knockout (DKO) pigs harboring edited knockout alleles for known receptor proteins CD163 and pAPN and show that DKO pigs are completely resistant to genotype 2 PRRSV and TGEV. We found no differences in meat-production or reproductive-performance traits between wild-type and DKO pigs, but detected increased iron in DKO muscle. Additional infection challenge experiments showed that DKO pigs exhibited decreased susceptibility to porcine deltacoronavirus (PDCoV), thus offering unprecedented in vivo evidence of pAPN as one of PDCoV receptors. Beyond showing that multiple gene edits can be combined in a livestock animal to achieve simultaneous resistance to two major viruses, our study introduces a valuable model for investigating infection mechanisms of porcine pathogenic viruses that exploit pAPN or CD163 for entry.

Nanoparticle-Based Strategies to Combat COVID-19.

Coronavirus disease 2019 (COVID-19) is the worst pandemic disease of the current millennium. This disease is caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first exhibited human-to-human transmission in December 2019 and has infected millions of people within months across 213 different countries. Its ability to be transmitted by asymptomatic carriers has put a massive strain on the currently available testing resources. Currently, there are no clinically proven therapeutic methods that clearly inhibit the effects of this virus, and COVID-19 vaccines are still in the development phase. Strategies need to be explored to expand testing capacities, to develop effective therapeutics, and to develop safe vaccines that provide lasting immunity. Nanoparticles (NPs) have been widely used in many medical applications, such as biosensing, drug delivery, imaging, and antimicrobial treatment. SARS-CoV-2 is an enveloped virus with particle-like characteristics and a diameter of 60–140 nm. Synthetic NPs can closely mimic the virus and interact strongly with its proteins due to their morphological similarities. Hence, NP-based strategies for tackling this virus have immense potential. NPs have been previously found to be effective tools against many viruses, especially against those from the Coronaviridae family. This Review outlines the role of NPs in diagnostics, therapeutics, and vaccination for the other two epidemic coronaviruses, the 2003 severe acute respiratory syndrome (SARS) virus and the 2012 Middle East respiratory syndrome (MERS) virus. We also highlight nanomaterial-based approaches to address other coronaviruses, such as human coronaviruses (HCoVs); feline coronavirus (FCoV); avian coronavirus infectious bronchitis virus (IBV); coronavirus models, such as porcine epidemic diarrhea virus (PEDV), porcine reproductive and respiratory syndrome virus (PRRSV), and transmissible gastroenteritis virus (TGEV); and other viruses that share similarities with SARS-CoV-2. This Review combines the salient principles from previous antiviral studies with recent research conducted on SARS-CoV-2 to outline NP-based strategies that can be used to combat COVID-19 and similar pandemics in the future.

Antiviral and virucidal effects of curcumin on transmissible gastroenteritis virus in vitro.

Emerging coronaviruses represent serious threats to human and animal health worldwide, and no approved therapeutics are currently available. Here, we used Transmissible gastroenteritis virus (TGEV) as the alpha-coronavirus model, and investigated the antiviral properties of curcumin against TGEV. Our results demonstrated that curcumin strongly inhibited TGEV proliferation and viral protein expression in a dose-dependent manner. We also observed that curcumin exhibited direct virucidal abilities in a dose-, temperature- and time-dependent manner. Furthermore, time-of-addition assays showed that curcumin mainly acted in the early phase of TGEV replication. Notably, in an adsorption assay, curcumin at 40 µM resulted in a reduction in viral titres of 3.55 log TCID50 ml-1, indicating that curcumin possesses excellent inhibitory effects on the adsorption of TGEV. Collectively, we demonstrate for the first time that curcumin has virucidal activity and virtual inhibition against TGEV, suggesting that curcumin might be a candidate drug for effective control of TGEV infection.

Dry Heat as a Decontamination Method for N95 Respirator Reuse.

A pandemic such as COVID-19 can cause a sudden depletion of the worldwide supply of respirators, forcing healthcare providers to reuse them. In this study, we systematically evaluated dry heat treatment as a viable option for the safe decontamination of N95 respirators (1860, 3M) before their reuse. We found that the dry heat generated by an electric cooker (100 °C, 5% relative humidity, 50 min) effectively inactivated Tulane virus (TV, >5.2-log10 reduction), rotavirus (RV, >6.6-log10 reduction), adenovirus (AdV, >4.0-log10 reduction), and transmissible gastroenteritis virus (TGEV, >4.7-log10 reduction). The respirator integrity (determined on the basis of the particle filtration efficiency and quantitative fit testing) was not compromised after 20 cycles of a 50 min dry heat treatment. On the basis of these results, dry heat decontamination generated by an electric cooker (e.g., rice cookers, instant pots, and ovens) could be an effective and accessible decontamination method for the safe reuse of N95 respirators. We recommend users measure the temperature during decontamination to ensure the respirator temperature can be maintained at 100 °C for 50 min.