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Virus Evolution 2024The lesser short-tailed bat () and the long-tailed bat () are Aotearoa New Zealand's only native extant terrestrial mammals and are believed to have migrated from...
The lesser short-tailed bat () and the long-tailed bat () are Aotearoa New Zealand's only native extant terrestrial mammals and are believed to have migrated from Australia. Long-tailed bats arrived in New Zealand an estimated two million years ago and are closely related to other Australian bat species. Lesser short-tailed bats, in contrast, are the only extant species within the Mystacinidae and are estimated to have been living in isolation in New Zealand for the past 16-18 million years. Throughout this period of isolation, lesser short-tailed bats have become one of the most terrestrial bats in the world. Through a metatranscriptomic analysis of guano samples from eight locations across New Zealand, we aimed to characterise the viromes of New Zealand's bats and determine whether viruses have jumped between these species over the past two million years. High viral richness was observed among long-tailed bats with viruses spanning seven different viral families. In contrast, no bat-specific viruses were identified in lesser short-tailed bats. Both bat species harboured an abundance of likely dietary- and environment-associated viruses. We also identified alphacoronaviruses in long-tailed bat guano that had previously been identified in lesser short-tailed bats, suggesting that these viruses had jumped the species barrier after long-tailed bats migrated to New Zealand. Of note, an alphacoronavirus species discovered here possessed a complete genome of only 22,416 nucleotides with entire deletions or truncations of several non-structural proteins, thereby representing what may be the shortest genome within the identified to date. Overall, this study has revealed a diverse range of novel viruses harboured by New Zealand's only native terrestrial mammals, in turn expanding our understanding of bat viral dynamics and evolution globally.
PubMed: 38379777
DOI: 10.1093/ve/veae008 -
Nature Communications Feb 2024Cepharanthine is a secondary metabolite isolated from Stephania. It has been reported that it has anti-conronaviruses activities including severe acute respiratory...
Cepharanthine is a secondary metabolite isolated from Stephania. It has been reported that it has anti-conronaviruses activities including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we assemble three Stephania genomes (S. japonica, S. yunnanensis, and S. cepharantha), propose the cepharanthine biosynthetic pathway, and assess the antiviral potential of compounds involved in the pathway. Among the three genomes, S. japonica has a near telomere-to-telomere assembly with one remaining gap, and S. cepharantha and S. yunnanensis have chromosome-level assemblies. Following by biosynthetic gene mining and metabolomics analysis, we identify seven cepharanthine analogs that have broad-spectrum anti-coronavirus activities, including SARS-CoV-2, Guangxi pangolin-CoV (GX_P2V), swine acute diarrhoea syndrome coronavirus (SADS-CoV), and porcine epidemic diarrhea virus (PEDV). We also show that two other genera, Nelumbo and Thalictrum, can produce cepharanthine analogs, and thus have the potential for antiviral compound discovery. Results generated from this study could accelerate broad-spectrum anti-coronavirus drug discovery.
Topics: Animals; Swine; Stephania; China; SARS-CoV-2; Antiviral Agents; Alphacoronavirus; Benzylisoquinolines; Benzodioxoles
PubMed: 38378731
DOI: 10.1038/s41467-024-45690-5 -
Veterinaria Italiana Jul 2023Feline Coronavirus (FCoV) is a worldwide viral infection of felids. The disease is usually asymptomatic, but it can cause mild diarrhoea; however, few numbers of cases...
Feline Coronavirus (FCoV) is a worldwide viral infection of felids. The disease is usually asymptomatic, but it can cause mild diarrhoea; however, few numbers of cases may develop a severe systemic disease known as feline infectious peritonitis (FIP). This study aims to determine the prevalence of FCoV shedding in the faeces of stray cats in Kuwait and detect antibodies against FCoV in their serum. Histopathological analyses and RT‑PCR were used to prove cases of FIP. A total of 178 cats were examined for the presence of FCoV in their faeces using a rapid immunochromatography (IC) test. Anti‑FCoV Antibody (Anti‑FCoV Ab) was detected in their serum using ELISA. Eleven samples were tested using RT‑PCR to confirm positive cases. The prevalence of FCoV faecal antigen in stray cats was 32.6%. The overall detection rate of Anti‑FCoV Ab in stray cats was 44.9%. Nine cats tested positive using the RT‑PCR test. Six out of those nine were confirmed to be FIP positive through gross and histopathological examination. The characteristic uveitis and discoloration of the irises were seen. The present study is the first report confirming FCoV infection in stray cats in Kuwait. Postmortem and histopathological lesions in cases of FIP were recorded.
Topics: Cats; Animals; Kuwait; Coronavirus, Feline; Cross-Sectional Studies; Autopsy; Coronavirus Infections; Cat Diseases
PubMed: 38376836
DOI: 10.12834/VetIt.2646.17310.3 -
Journal of Colloid and Interface Science May 2024Surfactants are inexpensive chemicals with promising applications in virus inactivation, particularly for enveloped viruses. Yet, the detailed mechanisms by which...
HYPOTHESIS
Surfactants are inexpensive chemicals with promising applications in virus inactivation, particularly for enveloped viruses. Yet, the detailed mechanisms by which surfactants deactivate coronaviruses remain underexplored. This study delves into the virucidal mechanisms of various surfactants on Feline Coronavirus (FCoV) and their potential applications against more pathogenic coronaviruses.
EXPERIMENTS
By integrating virucidal activity assays with fluorescence spectroscopy, dynamic light scattering and laser Doppler electrophoresis, alongside liposome permeability experiments, we have analyzed the effects of non-ionic and ionic surfactants on viral activity.
FINDINGS
The non-ionic surfactant octaethylene glycol monodecyl ether (CEO) inactivates the virus by disrupting the lipid envelope, whereas ionic surfactants like Sodium Dodecyl Sulfate and Cetylpyridinium Chloride predominantly affect the spike proteins, with their impact on the viral membrane being hampered by kinetic and thermodynamic constraints. FCoV served as a safe model for studying virucidal activity, offering a faster alternative to traditional virucidal assays. The study demonstrates that physicochemical techniques can expedite the screening of virucidal compounds, contributing to the design of effective disinfectant formulations. Our results not only highlight the critical role of surfactant-virus interactions but also contribute to strategic advancements in public health measures for future pandemic containment and the ongoing challenge of antimicrobial resistance.
Topics: Animals; Cats; Surface-Active Agents; Coronavirus, Feline; Sodium Dodecyl Sulfate; Virus Inactivation
PubMed: 38364478
DOI: 10.1016/j.jcis.2024.02.088 -
Virus Evolution 2024Understanding phylogenetic relationships among species is essential for many biological studies, which call for an accurate phylogenetic tree to understand major...
Understanding phylogenetic relationships among species is essential for many biological studies, which call for an accurate phylogenetic tree to understand major evolutionary transitions. The phylogenetic analyses present a major challenge in estimation accuracy and computational efficiency, especially recently facing a wave of severe emerging infectious disease outbreaks. Here, we introduced a novel, efficient framework called Bases-dependent Rapid Phylogenetic Clustering (Bd-RPC) for new sample placement for viruses. In this study, a brand-new recoding method called Frequency Vector Recoding was implemented to approximate the phylogenetic distance, and the Phylogenetic Simulated Annealing Search algorithm was developed to match the recoded distance matrix with the phylogenetic tree. Meanwhile, the indel (insertion/deletion) was heuristically introduced to foreign sequence recognition for the first time. Here, we compared the Bd-RPC with the recent placement software (PAGAN2, EPA-ng, TreeBeST) and evaluated it in , and by using Split and Robinson-Foulds distances. The comparisons showed that Bd-RPC maintained the highest precision with great efficiency, demonstrating good performance in new sample placement on all three virus genera. Finally, a user-friendly website (http://www.bd-rpc.xyz) is available for users to classify new samples instantly and facilitate exploration of the phylogenetic research in viruses, and the Bd-RPC is available on GitHub (http://github.com/Bin-Ma/bd-rpc).
PubMed: 38361823
DOI: 10.1093/ve/veae005 -
Frontiers in Immunology 2023Understanding how HIV affects SARS-CoV-2 immunity is crucial for managing COVID-19 in sub-Saharan populations due to frequent coinfections. Our previous research showed...
Low pre-existing endemic human coronavirus (HCoV-NL63)-specific T cell frequencies are associated with impaired SARS-CoV-2-specific T cell responses in people living with HIV.
BACKGROUND
Understanding how HIV affects SARS-CoV-2 immunity is crucial for managing COVID-19 in sub-Saharan populations due to frequent coinfections. Our previous research showed that unsuppressed HIV is associated with weaker immune responses to SARS-CoV-2, but the underlying mechanisms are unclear. We investigated how pre-existing T cell immunity against an endemic human coronavirus HCoV-NL63 impacts SARS-CoV-2 T cell responses in people living with HIV (PLWH) compared to uninfected individuals, and how HIV-related T cell dysfunction influences responses to SARS-CoV-2 variants.
METHODS
We used flow cytometry to measure T cell responses following PBMC stimulation with peptide pools representing beta, delta, wild-type, and HCoV-NL63 spike proteins. Luminex bead assay was used to measure circulating plasma chemokine and cytokine levels. ELISA and MSD V-PLEX COVID-19 Serology and ACE2 Neutralization assays were used to measure humoral responses.
RESULTS
Regardless of HIV status, we found a strong positive correlation between responses to HCoV-NL63 and SARS-CoV-2. However, PLWH exhibited weaker CD4 T cell responses to both HCoV-NL63 and SARS-CoV-2 than HIV-uninfected individuals. PLWH also had higher proportions of functionally exhausted (PD-1high) CD4 T cells producing fewer proinflammatory cytokines (IFNγ and TNFα) and had elevated plasma IL-2 and IL-12(p70) levels compared to HIV-uninfected individuals. HIV status didn't significantly affect IgG antibody levels against SARS-CoV-2 antigens or ACE2 binding inhibition activity.
CONCLUSION
Our results indicate that the decrease in SARS-CoV-2 specific T cell responses in PLWH may be attributable to reduced frequencies of pre-existing cross-reactive responses. However, HIV infection minimally affected the quality and magnitude of humoral responses, and this could explain why the risk of severe COVID-19 in PLWH is highly heterogeneous.
Topics: Humans; SARS-CoV-2; Coronavirus NL63, Human; COVID-19; Angiotensin-Converting Enzyme 2; HIV Infections; Leukocytes, Mononuclear; T-Lymphocytes; Cytokines
PubMed: 38343437
DOI: 10.3389/fimmu.2023.1291048 -
Microbiology Spectrum Mar 2024After 3 years of its introduction to humans, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared as endemic. Little is known about the...
UNLABELLED
After 3 years of its introduction to humans, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared as endemic. Little is known about the severity of the disease manifestation that future infections may cause, especially when reinfections occur after humoral immunity from a previous infection or vaccination has waned. Such knowledge could inform policymakers regarding the frequency of vaccination. Reinfections by endemic human coronaviruses (HCoVs) can serve as a model system for SARS-CoV-2 endemicity. We monitored 44 immunocompetent male adults with blood sampling every 6 months (for 17 years), for the frequency of HCoV (re-)infections, using rises in N-antibodies of HCoV-NL63, HCoV-29E, HCoV-OC43, and HCoV-HKU1 as markers of infection. Disease associations during (re-)infections were examined by comparison of self-reporting records of influenza-like illness (ILI) symptoms, every 6 months, by all participants. During 8,549 follow-up months, we found 364 infections by any HCoV with a median of eight infections per person. Symptoms more frequently reported during HCoV infection were cough, sore throat, and myalgia. Two hundred fifty-one of the 364 infections were species-specific HCoV-reinfections, with a median interval of 3.58 (interquartile range 1.92-5.67) years. The length of the interval between reinfections-being either short or long-had no influence on the frequency of reporting ILI symptoms. All HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1 (re-)infections are associated with the reporting of ILIs. Importantly, in immunocompetent males, these symptoms are not influenced by the length of the interval between reinfections.
IMPORTANCE
Little is known about the disease following human coronavirus (HCoV) reinfection occurring years after the previous infection, once humoral immunity has waned. We monitored endemic HCoV reinfection in immunocompetent male adults for up to 17 years. We found no influence of reinfection interval length in the disease manifestation, suggesting that immunocompetent male adults are adequately protected against future HCoV infections.
Topics: Adult; Humans; Male; Reinfection; Influenza, Human; Respiratory Tract Infections; Coronavirus 229E, Human; Coronavirus OC43, Human; SARS-CoV-2; Coronavirus NL63, Human
PubMed: 38329364
DOI: 10.1128/spectrum.03912-23 -
Frontiers in Immunology 2024The present study was conducted to decipher the protection effects of ellagic acid (EA) on piglets infected with porcine epidemic diarrhea virus (PEDV). Thirty 7-day-old...
The present study was conducted to decipher the protection effects of ellagic acid (EA) on piglets infected with porcine epidemic diarrhea virus (PEDV). Thirty 7-day-old piglets were randomly assigned to three treatment groups: control, PEDV, and EA + PEDV groups. After a 3-day period of adaption, piglets in the EA + PEDV group were orally administered with 20 mg/kg·BW EA during days 4-11 of the trial. On day 8, piglets were orally administered with PEDV at a dose of 10 TCID (50% tissue culture infectious dose) per pig. Additionally, intestinal porcine epithelial (IPEC-1) cells infected with PEDV were used to investigate the anti-PEDV effect of EA . The results showed that EA at a dose of 10-40 μmol/L increased the viability of PEDV-infected IPEC-1 cells, and EA administration mitigated intestinal edema in piglets challenged with PEDV. Further studies indicated that EA treatment significantly increased the proportion of white blood cells in blood and concentrations of IL-6, IL-1β, and IL-10 in the serum, but decreased the TNF-α content and gene expression of , , , and in the jejunum. Moreover, EA intervention considerably elevated the activity of total superoxide dismutase (T-SOD), but decreased the HO concentration in the ileum of piglets. Importantly, EA suppressed the increased expression of antiviral-related genes and proteins (including MXI, ISG15, HSP70, and p-IRF7) induced by PEDV challenge in the jejunum. Furthermore, PEDV infection increased the protein abundance of p-JAK2 and p-STAT3, which were further enhanced by EA supplementation. In conclusion, our results revealed that EA could promote the restoration of intestinal homeostasis by regulating the interferon pathway that was interrelated with the activation of JAK2/STAT3 signaling. These findings provide theoretical basis for the use of EA as a therapy targeting PEDV infection in piglets.
Topics: Swine; Animals; Porcine epidemic diarrhea virus; Ellagic Acid; Tumor Necrosis Factor-alpha; Hydrogen Peroxide; Interleukin-6
PubMed: 38322259
DOI: 10.3389/fimmu.2024.1323866 -
Frontiers in Immunology 2024CpG oligodeoxynucleotides (CpG ODNs) boost the humoral and cellular immune responses to antigens through interaction with Toll-like receptor 9 (TLR9). These CpG ODNs...
CpG oligodeoxynucleotides (CpG ODNs) boost the humoral and cellular immune responses to antigens through interaction with Toll-like receptor 9 (TLR9). These CpG ODNs have been extensively utilized in human vaccines. In our study, we evaluated five B-type CpG ODNs that have stimulatory effects on pigs by measuring the proliferation of porcine peripheral blood mononuclear cells (PBMCs) and assessing interferon gamma (IFN-γ) secretion. Furthermore, this study examined the immunoenhancing effects of the MF59 and CpG ODNs compound adjuvant in mouse and piglet models of porcine epidemic diarrhea virus (PEDV) subunit vaccine administration. The screening revealed that the CpG ODN named CpG5 significantly stimulated the proliferation of porcine PBMCs and elevated IFN-γ secretion levels. In the mouse vaccination model, CpG5 compound adjuvant significantly bolstered the humoral and cellular immune responses to the PEDV subunit vaccines, leading to Th1 immune responses characterized by increased IFN-γ and IgG2a levels. In piglets, the neutralizing antibody titer was significantly enhanced with CpG5 compound adjuvant, alongside a considerable increase in CD8+ T lymphocytes proportion. The combination of MF59 adjuvant and CpG5 exhibits a synergistic effect, resulting in an earlier, more intense, and long-lasting immune response in subunit vaccines for PEDV. This combination holds significant promise as a robust candidate for the development of vaccine adjuvant.
Topics: Animals; Swine; Mice; Humans; Porcine epidemic diarrhea virus; Leukocytes, Mononuclear; Adjuvants, Immunologic; Immunity; Vaccines, Subunit; Adjuvants, Pharmaceutic; Oligodeoxyribonucleotides; Polysorbates; Squalene
PubMed: 38322258
DOI: 10.3389/fimmu.2024.1336239 -
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