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2.
J Gen Virol ; 102(10)2021 10.
Article in English | MEDLINE | ID: covidwho-1490495

ABSTRACT

The highly pathogenic Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a severe respiratory virus. Recent reports indicate additional central nervous system (CNS) involvement. In this study, human DPP4 transgenic mice were infected with MERS-CoV, and viral antigens were first detected in the midbrain-hindbrain 4 days post-infection, suggesting the virus may enter the brainstem via peripheral nerves. Neurons and astrocytes throughout the brain were infected, followed by damage of the blood brain barrier (BBB), as well as microglial activation and inflammatory cell infiltration, which may be caused by complement activation based on the observation of deposition of complement activation product C3 and high expression of C3a receptor (C3aR) and C5a receptor (C5aR1) in neurons and glial cells. It may be concluded that these effects were mediated by complement activation in the brain, because of their reduction resulted from the treatment with mouse C5aR1-specific mAb. Such mAb significantly reduced nucleoprotein expression, suppressed microglial activation and decreased activation of caspase-3 in neurons and p38 phosphorylation in the brain. Collectively, these results suggest that MERS-CoV infection of CNS triggers complement activation, leading to inflammation-mediated damage of brain tissue, and regulating of complement activation could be a promising intervention and adjunctive treatment for CNS injury by MERS-CoV and other coronaviruses.


Subject(s)
Brain/pathology , Complement System Proteins/immunology , Coronavirus Infections/pathology , Dipeptidyl Peptidase 4/genetics , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Animals , Blood-Brain Barrier/immunology , Blood-Brain Barrier/pathology , Brain/blood supply , Brain/immunology , Brain/virology , Complement Activation/drug effects , Complement Inactivating Agents/therapeutic use , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/virology , Disease Models, Animal , Humans , Inflammation , Mice , Mice, Transgenic , Microglia/immunology , Microglia/pathology
5.
Proc Natl Acad Sci U S A ; 118(43)2021 10 26.
Article in English | MEDLINE | ID: covidwho-1481965

ABSTRACT

Self-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) produces a replication-competent propagation-defective RNA replicon (MERS-CoV-ΔE). Evaluation of this replicon in mice expressing human dipeptidyl peptidase 4, the virus receptor, showed that the single deletion of the E gene generated an attenuated mutant. The combined deletion of the E gene with accessory open reading frames (ORFs) 3, 4a, 4b, and 5 resulted in a highly attenuated propagation-defective RNA replicon (MERS-CoV-Δ[3,4a,4b,5,E]). This RNA replicon induced sterilizing immunity in mice after challenge with a lethal dose of a virulent MERS-CoV, as no histopathological damage or infectious virus was detected in the lungs of challenged mice. The four mutants lacking the E gene were genetically stable, did not recombine with the E gene provided in trans during their passage in cell culture, and showed a propagation-defective phenotype in vivo. In addition, immunization with MERS-CoV-Δ[3,4a,4b,5,E] induced significant levels of neutralizing antibodies, indicating that MERS-CoV RNA replicons are highly safe and promising vaccine candidates.


Subject(s)
Coronavirus Infections/prevention & control , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/immunology , RNA, Viral/administration & dosage , Replicon , Viral Vaccines/administration & dosage , Animals , Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Coronavirus Infections/virology , Defective Viruses/genetics , Defective Viruses/immunology , Female , Gene Deletion , Genes, env , Humans , Mice , Mice, Inbred C57BL , Mice, Transgenic , Middle East Respiratory Syndrome Coronavirus/pathogenicity , RNA, Viral/genetics , RNA, Viral/immunology , Vaccines, Virus-Like Particle/administration & dosage , Vaccines, Virus-Like Particle/genetics , Vaccines, Virus-Like Particle/immunology , Viral Vaccines/genetics , Viral Vaccines/immunology , Virulence/genetics , Virulence/immunology
6.
J Virol ; 95(22): e0127621, 2021 10 27.
Article in English | MEDLINE | ID: covidwho-1494956

ABSTRACT

The emergence of life-threatening zoonotic diseases caused by betacoronaviruses, including the ongoing coronavirus disease 19 (COVID-19) pandemic, has highlighted the need for developing preclinical models mirroring respiratory and systemic pathophysiological manifestations seen in infected humans. Here, we showed that C57BL/6J wild-type mice intranasally inoculated with the murine betacoronavirus murine hepatitis coronavirus 3 (MHV-3) develop a robust inflammatory response leading to acute lung injuries, including alveolar edema, hemorrhage, and fibrin thrombi. Although such histopathological changes seemed to resolve as the infection advanced, they efficiently impaired respiratory function, as the infected mice displayed restricted lung distention and increased respiratory frequency and ventilation. Following respiratory manifestation, the MHV-3 infection became systemic, and a high virus burden could be detected in multiple organs along with morphological changes. The systemic manifestation of MHV-3 infection was also marked by a sharp drop in the number of circulating platelets and lymphocytes, besides the augmented concentration of the proinflammatory cytokines interleukin 1 beta (IL-1ß), IL-6, IL-12, gamma interferon (IFN-γ), and tumor necrosis factor (TNF), thereby mirroring some clinical features observed in moderate and severe cases of COVID-19. Importantly, both respiratory and systemic changes triggered by MHV-3 infection were greatly prevented by blocking TNF signaling, either via genetic or pharmacologic approaches. In line with this, TNF blockage also diminished the infection-mediated release of proinflammatory cytokines and virus replication of human epithelial lung cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Collectively, results show that MHV-3 respiratory infection leads to a large range of clinical manifestations in mice and may constitute an attractive, lower-cost, biosafety level 2 (BSL2) in vivo platform for evaluating the respiratory and multiorgan involvement of betacoronavirus infections. IMPORTANCE Mouse models have long been used as valuable in vivo platforms to investigate the pathogenesis of viral infections and effective countermeasures. The natural resistance of mice to the novel betacoronavirus SARS-CoV-2, the causative agent of COVID-19, has launched a race toward the characterization of SARS-CoV-2 infection in other animals (e.g., hamsters, cats, ferrets, bats, and monkeys), as well as adaptation of the mouse model, by modifying either the host or the virus. In the present study, we utilized a natural pathogen of mice, MHV, as a prototype to model betacoronavirus-induced acute lung injure and multiorgan involvement under biosafety level 2 conditions. We showed that C57BL/6J mice intranasally inoculated with MHV-3 develops severe disease, which includes acute lung damage and respiratory distress that precede systemic inflammation and death. Accordingly, the proposed animal model may provide a useful tool for studies regarding betacoronavirus respiratory infection and related diseases.


Subject(s)
Coronavirus Infections/pathology , Disease Models, Animal , Lung/pathology , Murine hepatitis virus/pathogenicity , Animals , Cell Line , Containment of Biohazards , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cytokines/metabolism , Humans , Inflammation , Liver/pathology , Liver/virology , Lung/virology , Mice , Murine hepatitis virus/drug effects , Murine hepatitis virus/physiology , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolism , Virus Replication/drug effects
7.
Sci Rep ; 10(1): 16598, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-1493167

ABSTRACT

We address the diffusion of information about the COVID-19 with a massive data analysis on Twitter, Instagram, YouTube, Reddit and Gab. We analyze engagement and interest in the COVID-19 topic and provide a differential assessment on the evolution of the discourse on a global scale for each platform and their users. We fit information spreading with epidemic models characterizing the basic reproduction number [Formula: see text] for each social media platform. Moreover, we identify information spreading from questionable sources, finding different volumes of misinformation in each platform. However, information from both reliable and questionable sources do not present different spreading patterns. Finally, we provide platform-dependent numerical estimates of rumors' amplification.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Social Media , Basic Reproduction Number , COVID-19 , Coronavirus Infections/virology , Data Analysis , Humans , Information Dissemination , Linear Models , Neural Networks, Computer , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Social Behavior
9.
Int J Mol Sci ; 22(21)2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1488619

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to global public health and the economy. The enzymatic product of cholesterol 25-hydroxylase (CH25H), 25-Hydroxycholesterol (25-HC), was reported to have potent anti-SARS-CoV-2 activity. Here, we found that the combination of 25-HC with EK1 peptide, a pan-coronavirus (CoV) fusion inhibitor, showed a synergistic antiviral activity. We then used the method of 25-HC modification to design and synthesize a series of 25-HC-modified peptides and found that a 25-HC-modified EK1 peptide (EK1P4HC) was highly effective against infections caused by SARS-CoV-2, its variants of concern (VOCs), and other human CoVs, such as HCoV-OC43 and HCoV-229E. EK1P4HC could protect newborn mice from lethal HCoV-OC43 infection, suggesting that conjugation of 25-HC with a peptide-based viral inhibitor was a feasible and universal strategy to improve its antiviral activity.


Subject(s)
Antiviral Agents/pharmacology , Hydroxycholesterols/chemistry , Lipopeptides/chemistry , SARS-CoV-2/drug effects , Amino Acid Sequence , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Body Weight/drug effects , COVID-19/drug therapy , COVID-19/virology , Coronavirus 229E, Human/drug effects , Coronavirus 229E, Human/pathogenicity , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Coronavirus Infections/virology , Coronavirus OC43, Human/drug effects , Coronavirus OC43, Human/pathogenicity , Disease Models, Animal , Drug Synergism , Humans , Hydroxycholesterols/pharmacology , Hydroxycholesterols/therapeutic use , Lipopeptides/pharmacology , Lipopeptides/therapeutic use , Mice , Mice, Inbred BALB C , Polyethylene Glycols/chemistry , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Survival Rate , Virus Internalization/drug effects
10.
J Virol ; 95(16): e0018721, 2021 07 26.
Article in English | MEDLINE | ID: covidwho-1486048

ABSTRACT

Subversion of the host cell cycle to facilitate viral replication is a common feature of coronavirus infections. Coronavirus nucleocapsid (N) protein can modulate the host cell cycle, but the mechanistic details remain largely unknown. Here, we investigated the effects of manipulation of porcine epidemic diarrhea virus (PEDV) N protein on the cell cycle and the influence on viral replication. Results indicated that PEDV N induced Vero E6 cell cycle arrest at S-phase, which promoted viral replication (P < 0.05). S-phase arrest was dependent on the N protein nuclear localization signal S71NWHFYYLGTGPHADLRYRT90 and the interaction between N protein and p53. In the nucleus, the binding of N protein to p53 maintained consistently high-level expression of p53, which activated the p53-DREAM pathway. The key domain of the N protein interacting with p53 was revealed to be S171RGNSQNRGNNQGRGASQNRGGNN194 (NS171-N194), in which G183RG185 are core residues. NS171-N194 and G183RG185 were essential for N-induced S-phase arrest. Moreover, small molecular drugs targeting the NS171-N194 domain of the PEDV N protein were screened through molecular docking. Hyperoside could antagonize N protein-induced S-phase arrest by interfering with interaction between N protein and p53 and inhibit viral replication (P < 0.05). The above-described experiments were also validated in porcine intestinal cells, and data were in line with results in Vero E6 cells. Therefore, these results reveal the PEDV N protein interacts with p53 to activate the p53-DREAM pathway, and subsequently induces S-phase arrest to create a favorable environment for virus replication. These findings provide new insight into the PEDV-host interaction and the design of novel antiviral strategies against PEDV. IMPORTANCE Many viruses subvert the host cell cycle to create a cellular environment that promotes viral growth. PEDV, an emerging and reemerging coronavirus, has led to substantial economic loss in the global swine industry. Our study is the first to demonstrate that PEDV N-induced cell cycle arrest during the S-phase promotes viral replication. We identified a novel mechanism of PEDV N-induced S-phase arrest, where the binding of PEDV N protein to p53 maintains consistently high levels of p53 expression in the nucleus to mediate S-phase arrest by activating the p53-DREAM pathway. Furthermore, a small molecular compound, hyperoside, targeted the PEDV N protein, interfering with the interaction between the N protein and p53 and, importantly, inhibited PEDV replication by antagonizing cell cycle arrest. This study reveals a new mechanism of PEDV-host interaction and also provides a novel antiviral strategy for PEDV. These data provide a foundation for further research into coronavirus-host interactions.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus Nucleocapsid Proteins/chemistry , Host-Pathogen Interactions/drug effects , Porcine epidemic diarrhea virus/drug effects , Quercetin/analogs & derivatives , Tumor Suppressor Protein p53/chemistry , Amino Acid Sequence , Animals , Antiviral Agents/chemistry , Binding Sites , Cell Line , Chlorocebus aethiops , Coronavirus Infections/drug therapy , Coronavirus Infections/genetics , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Coronavirus Nucleocapsid Proteins/antagonists & inhibitors , Coronavirus Nucleocapsid Proteins/genetics , Coronavirus Nucleocapsid Proteins/metabolism , Epithelial Cells/drug effects , Epithelial Cells/virology , Gene Expression Regulation , High-Throughput Screening Assays , Host-Pathogen Interactions/genetics , Molecular Docking Simulation , Nuclear Localization Signals , Porcine epidemic diarrhea virus/genetics , Porcine epidemic diarrhea virus/metabolism , Protein Binding , Protein Conformation , Protein Interaction Domains and Motifs , Quercetin/chemistry , Quercetin/pharmacology , S Phase Cell Cycle Checkpoints/drug effects , S Phase Cell Cycle Checkpoints/genetics , Signal Transduction , Swine , Swine Diseases/drug therapy , Swine Diseases/genetics , Swine Diseases/metabolism , Swine Diseases/virology , Tumor Suppressor Protein p53/antagonists & inhibitors , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Vero Cells , Virus Replication/drug effects
11.
Virus Res ; 306: 198566, 2021 12.
Article in English | MEDLINE | ID: covidwho-1475120

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, China, and rapidly spread throughout the world. This newly emerging pathogen is highly transmittable and can cause fatal disease. More than 35 million cases have been confirmed, with a fatality rate of about 2.9% to October 9, 2020. However, the original and intermediate hosts of SARS-CoV-2 remain unknown. Here, 3160 poultry samples collected from 14 provinces of China between September and December 2019 were tested for SARS-CoV-2 infection. All the samples were SARS-CoV-2 negative, but 593 avian coronaviruses were detected, including 485 avian infectious bronchitis viruses, 72 duck coronaviruses, and 36 pigeon coronaviruses, with positivity rates of 15.35%, 2.28%, and 1.14%, respectively. Our surveillance demonstrates the diversity of avian coronaviruses in China, with higher prevalence rates in some regions. Furthermore, the possibility that SARS-CoV-2 originated from a known avian-origin coronavirus can be preliminarily ruled out. More surveillance of and research into avian coronaviruses are required to better understand the diversity, distribution, cross-species transmission, and clinical significance of these viruses.


Subject(s)
Bird Diseases/virology , Coronavirus Infections/veterinary , Coronavirus/genetics , Coronavirus/isolation & purification , Genetic Variation , Animals , Bird Diseases/epidemiology , Chickens/virology , China/epidemiology , Columbidae/virology , Coronavirus/classification , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Ducks/virology , Epidemiological Monitoring , Geese/virology , Phylogeny , Poultry Diseases/epidemiology , Poultry Diseases/virology , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification
13.
Viruses ; 13(10)2021 10 14.
Article in English | MEDLINE | ID: covidwho-1469383

ABSTRACT

The human Betacoronavirus OC43 is a common cause of respiratory viral infections in adults and children. Lung infections with OC43 are associated with mortality, especially in hematopoietic stem cell transplant recipients. Neutralizing antibodies play a major role in protection against many respiratory viral infections, but to date a live viral neutralization assay for OC43 has not been described. We isolated a human monoclonal antibody (OC2) that binds to the spike protein of OC43 and neutralizes the live virus derived from the original isolate of OC43. We used this monoclonal antibody to develop and test the performance of two readily accessible in vitro assays for measuring antibody neutralization, one utilizing cytopathic effect and another utilizing an ELISA of infected cells. We used both methods to measure the neutralizing activity of the OC2 monoclonal antibody and of human plasma. These assays could prove useful for studying humoral responses to OC43 and cross-neutralization with other medically important betacoronaviruses.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Coronavirus OC43, Human/immunology , Neutralization Tests/methods , Spike Glycoprotein, Coronavirus/immunology , Cell Line , Common Cold/immunology , Common Cold/pathology , Common Cold/virology , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Enzyme-Linked Immunosorbent Assay/methods , Humans
15.
J Med Ethics ; 46(8): 505-507, 2020 08.
Article in English | MEDLINE | ID: covidwho-1467731

ABSTRACT

COVID-19 is reducing the ability to perform surgical procedures worldwide, giving rise to a multitude of ethical, practical and medical dilemmas. Adapting to crisis conditions requires a rethink of traditional best practices in surgical management, delving into an area of unknown risk profiles. Key challenging areas include cancelling elective operations, modifying procedures to adapt local services and updating the consenting process. We aim to provide an ethical rationale to support change in practice and guide future decision-making. Using the four principles approach as a structure, Medline was searched for existing ethical frameworks aimed at resolving conflicting moral duties. Where insufficient data were available, best guidance was sought from educational institutions: National Health Service England and The Royal College of Surgeons. Multiple papers presenting high-quality, reasoned, ethical theory and practice guidance were collected. Using this as a basis to assess current practice, multiple requirements were generated to ensure preservation of ethical integrity when making management decisions. Careful consideration of ethical principles must guide production of local guidance ensuring consistent patient selection thus preserving equality as well as quality of clinical services. A critical issue is balancing the benefit of surgery against the unknown risk of developing COVID-19 and its associated complications. As such, the need for surgery must be sufficiently pressing to proceed with conventional or non-conventional operative management; otherwise, delaying intervention is justified. For delayed operations, it is our duty to quantify the long-term impact on patients' outcome within the constraints of pandemic management and its long-term outlook.


Subject(s)
Coronavirus Infections/complications , Decision Making/ethics , Ethics, Medical , General Surgery/ethics , Health Equity/ethics , Pandemics/ethics , Patient Selection/ethics , Pneumonia, Viral/complications , Betacoronavirus , COVID-19 , Coronavirus Infections/virology , Cost-Benefit Analysis , England , Ethical Analysis , Ethical Theory , Humans , Informed Consent/ethics , Moral Obligations , Pneumonia, Viral/virology , Practice Guidelines as Topic , Principle-Based Ethics , Risk Assessment , SARS-CoV-2 , State Medicine , Surgeons , Surgical Procedures, Operative
16.
J Med Ethics ; 46(8): 510-513, 2020 08.
Article in English | MEDLINE | ID: covidwho-1467730

ABSTRACT

During the COVID-19 pandemic, the media have repeatedly praised healthcare workers for their 'heroic' work. Although this gratitude is undoubtedly appreciated by many, we must be cautious about overuse of the term 'hero' in such discussions. The challenges currently faced by healthcare workers are substantially greater than those encountered in their normal work, and it is understandable that the language of heroism has been evoked to praise them for their actions. Yet such language can have potentially negative consequences. Here, I examine what heroism is and why it is being applied to the healthcare workers currently, before outlining some of the problems associated with the heroism narrative currently being employed by the media. Healthcare workers have a clear and limited duty to treat during the COVID-19 pandemic, which can be grounded in a broad social contract and is strongly associated with certain reciprocal duties that society has towards healthcare workers. I argue that the heroism narrative can be damaging, as it stifles meaningful discussion about what the limits of this duty to treat are. It fails to acknowledge the importance of reciprocity, and through its implication that all healthcare workers have to be heroic, it can have negative psychological effects on workers themselves. I conclude that rather than invoking the language of heroism to praise healthcare workers, we should examine, as a society, what duties healthcare workers have to work in this pandemic, and how we can support them in fulfilling these.


Subject(s)
Coronavirus Infections , Courage , Delivery of Health Care , Health Personnel , Mass Media , Pandemics , Pneumonia, Viral , Public Opinion , Attitude to Health , Betacoronavirus , COVID-19 , Communication , Coronavirus Infections/virology , Humans , Moral Obligations , Pneumonia, Viral/virology , SARS-CoV-2 , Social Responsibility
17.
J Med Ethics ; 46(8): 495-498, 2020 08.
Article in English | MEDLINE | ID: covidwho-1467727

ABSTRACT

Key ethical challenges for healthcare workers arising from the COVID-19 pandemic are identified: isolation and social distancing, duty of care and fair access to treatment. The paper argues for a relational approach to ethics which includes solidarity, relational autonomy, duty, equity, trust and reciprocity as core values. The needs of the poor and socially disadvantaged are highlighted. Relational autonomy and solidarity are explored in relation to isolation and social distancing. Reciprocity is discussed with reference to healthcare workers' duty of care and its limits. Priority setting and access to treatment raise ethical issues of utility and equity. Difficult ethical dilemmas around triage, do not resuscitate decisions, and withholding and withdrawing treatment are discussed in the light of recently published guidelines. The paper concludes with the hope for a wider discussion of relational ethics and a glimpse of a future after the pandemic has subsided.


Subject(s)
Decision Making/ethics , Ethics, Clinical , Health Care Rationing/ethics , Health Equity/ethics , Health Personnel/ethics , Pandemics/ethics , Betacoronavirus , COVID-19 , Coronavirus Infections/virology , Disaster Planning , Humans , Moral Obligations , Pneumonia, Viral/virology , Poverty , Practice Guidelines as Topic , Professional-Patient Relations , Resuscitation Orders , SARS-CoV-2 , Social Values , Triage/ethics , Vulnerable Populations , Withholding Treatment/ethics
18.
J Med Ethics ; 46(8): 514-525, 2020 08.
Article in English | MEDLINE | ID: covidwho-1467726

ABSTRACT

BACKGROUND: Humanitarian crises and emergencies, events often marked by high mortality, have until recently excluded palliative care-a specialty focusing on supporting people with serious or terminal illness or those nearing death. In the COVID-19 pandemic, palliative care has received unprecedented levels of societal attention. Unfortunately, this has not been enough to prevent patients dying alone, relatives not being able to say goodbye and palliative care being used instead of intensive care due to resource limitations. Yet global guidance was available. In 2018, the WHO released a guide on 'Integrating palliative care and symptom relief into the response to humanitarian emergencies and crises'-the first guidance on the topic by an international body. AIMS: This paper argues that while a landmark document, the WHO guide took a narrowly clinical bioethics perspective and missed crucial moral dilemmas. We argue for adding a population-level bioethics lens, which draws forth complex moral dilemmas arising from the fact that groups having differential innate and acquired resources in the context of social and historical determinants of health. We discuss dilemmas concerning: limitations of material and human resources; patient prioritisation; euthanasia; and legacy inequalities, discrimination and power imbalances. IMPLICATIONS: In parts of the world where opportunity for preparation still exists, and as countries emerge from COVID-19, planners must consider care for the dying. Immediate steps to support better resolutions to ethical dilemmas of the provision of palliative care in humanitarian and emergency contexts will require honest debate; concerted research effort; and international, national and local ethical guidance.


Subject(s)
Bioethical Issues , Delivery of Health Care/ethics , Disaster Planning , Palliative Care/ethics , Pandemics/ethics , Terminal Care/ethics , Altruism , Betacoronavirus , Bioethics , COVID-19 , Coronavirus Infections/therapy , Coronavirus Infections/virology , Critical Care , Decision Making/ethics , Emergencies , Ethics, Clinical , Global Health , Health Care Rationing , Health Equity , Health Resources , Humans , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , Practice Guidelines as Topic , SARS-CoV-2 , Socioeconomic Factors , Stress, Psychological
19.
ACS Appl Mater Interfaces ; 13(41): 48469-48477, 2021 Oct 20.
Article in English | MEDLINE | ID: covidwho-1461961

ABSTRACT

The COVID-19 pandemic highlighted the importance of developing surfaces and coatings with antiviral activity. Here, we present, for the first time, peptide-based assemblies that can kill viruses. The minimal inhibitory concentration (MIC) of the assemblies is in the range tens of micrograms per milliliter. This value is 2 orders of magnitude smaller than the MIC of metal nanoparticles. When applied on a surface, by drop casting, the peptide spherical assemblies adhere to the surface and form an antiviral coating against both RNA- and DNA-based viruses including coronavirus. Our results show that the coating reduced the number of T4 bacteriophages (DNA-based virus) by 3 log, compared with an untreated surface and 6 log, when compared with a stock solution. Importantly, we showed that this coating completely inactivated canine coronavirus (RNA-based virus). This peptide-based coating can be useful wherever sterile surfaces are needed to reduce the risk of viral transmission.


Subject(s)
Antiviral Agents/chemistry , Peptides/chemistry , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Bacteriophages/drug effects , COVID-19/drug therapy , COVID-19/virology , Coronavirus/drug effects , Coronavirus/isolation & purification , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Dihydroxyphenylalanine/chemistry , Dog Diseases/drug therapy , Dog Diseases/virology , Dogs , Humans , Metal Nanoparticles/chemistry , Peptides/pharmacology , Peptides/therapeutic use , SARS-CoV-2/isolation & purification , Virus Inactivation/drug effects
20.
Viruses ; 13(10)2021 10 11.
Article in English | MEDLINE | ID: covidwho-1460086

ABSTRACT

Coronavirus, an important zoonotic disease, raises concerns of future pandemics. The bat is considered a source of noticeable viruses resulting in human and livestock infections, especially the coronavirus. Therefore, surveillance and genetic analysis of coronaviruses in bats are essential in order to prevent the risk of future diseases. In this study, the genome of HCQD-2020, a novel alphacoronavirus detected in a bat (Eptesicus serotinus), was assembled and described using next-generation sequencing and bioinformatics analysis. The comparison of the whole-genome sequence and the conserved amino acid sequence of replicated proteins revealed that the new strain was distantly related with other known species in the Alphacoronavirus genus. Phylogenetic construction indicated that this strain formed a separated branch with other species, suggesting a new species of Alphacoronavirus. Additionally, in silico prediction also revealed the risk of cross-species infection of this strain, especially in the order Artiodactyla. In summary, this study provided the genetic characteristics of a possible new species belonging to Alphacoronavirus.


Subject(s)
Alphacoronavirus/classification , Alphacoronavirus/genetics , Chiroptera/virology , Coronavirus Infections/veterinary , Genome, Viral/genetics , Alphacoronavirus/isolation & purification , Amino Acid Sequence/genetics , Animals , Artiodactyla/virology , Coronavirus Infections/virology , Phylogeny , Republic of Korea , Sequence Alignment , Whole Genome Sequencing
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