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1.
Iran J Allergy Asthma Immunol ; 19(5): 456-470, 2020 Oct 18.
Article in English | MEDLINE | ID: covidwho-1068112

ABSTRACT

The new coronavirus, known as "SARS-CoV-2"; is the cause of one of the most prevalent infectious viral diseases that was recently announced pandemic by the world health organization. Ongoing research in the fields of prevention, management, and therapy establishes a functional scaffold for clinics during the time of crisis. To obtain this goal, it is necessary that all pathophysiologic aspects of COVID-19 from infection to predisposing backgrounds of infection be identified, so that all the ambiguities of researchers regarding transmission mechanisms, variable clinical manifestation, and therapeutic response can be solved. Here, we firstly discuss about the homology screening between nCoV-2019 and beta-coronavirus family using phylogenetic analyses. Secondly, we analyzed the viral motifs to show that viral entry into the host cells requires a primary activation step performed by FURIN and FURIN-like-mediated enzymatic cleavage on the structural glycoprotein. The cleavage increases viral performance by 1000 folds. We then present a comprehensive view on host cells and the significance of gene variants affecting activation enzymes, supportive entry, and spread mechanisms in humans including renin-angiotensin-aldosterone system (RAAS) a pathway results in certain phenotypes or exacerbate infection-related phenotypes in different organs, hence causes variable clinical manifestations. This is followed by discussing about the importance of personalized medicine in nCoV-2019 exposure. Moreover, chemical drugs prescribed for individuals affected with COVID-19, as well as genes involved in drug transport and metabolisms are reviewed as a prelude to drug response. Finally, we suggest some therapeutic approaches developed based on new methods and technology such as anti-sense therapy and antibodies.


Subject(s)
/genetics , Furin/genetics , Spike Glycoprotein, Coronavirus/genetics , ADAM17 Protein/genetics , ADAM17 Protein/metabolism , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Betacoronavirus/genetics , /physiopathology , Enzyme Inhibitors/therapeutic use , Furin/metabolism , Genetic Predisposition to Disease , Genome, Human , Genome, Viral , Humans , Hydroxychloroquine/therapeutic use , Phylogeny , Precision Medicine , /metabolism , Renin-Angiotensin System/genetics , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization
2.
Int J Mol Sci ; 22(3)2021 Jan 28.
Article in English | MEDLINE | ID: covidwho-1055069

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel epidemic strain of Betacoronavirus that is responsible for the current viral pandemic, coronavirus disease 2019 (COVID-19), a global health crisis. Other epidemic Betacoronaviruses include the 2003 SARS-CoV-1 and the 2009 Middle East Respiratory Syndrome Coronavirus (MERS-CoV), the genomes of which, particularly that of SARS-CoV-1, are similar to that of the 2019 SARS-CoV-2. In this extensive review, we document the most recent information on Coronavirus proteins, with emphasis on the membrane proteins in the Coronaviridae family. We include information on their structures, functions, and participation in pathogenesis. While the shared proteins among the different coronaviruses may vary in structure and function, they all seem to be multifunctional, a common theme interconnecting these viruses. Many transmembrane proteins encoded within the SARS-CoV-2 genome play important roles in the infection cycle while others have functions yet to be understood. We compare the various structural and nonstructural proteins within the Coronaviridae family to elucidate potential overlaps and parallels in function, focusing primarily on the transmembrane proteins and their influences on host membrane arrangements, secretory pathways, cellular growth inhibition, cell death and immune responses during the viral replication cycle. We also offer bioinformatic analyses of potential viroporin activities of the membrane proteins and their sequence similarities to the Envelope (E) protein. In the last major part of the review, we discuss complement, stimulation of inflammation, and immune evasion/suppression that leads to CoV-derived severe disease and mortality. The overall pathogenesis and disease progression of CoVs is put into perspective by indicating several stages in the resulting infection process in which both host and antiviral therapies could be targeted to block the viral cycle. Lastly, we discuss the development of adaptive immunity against various structural proteins, indicating specific vulnerable regions in the proteins. We discuss current CoV vaccine development approaches with purified proteins, attenuated viruses and DNA vaccines.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/metabolism , Viral Matrix Proteins/metabolism , Animals , Betacoronavirus/genetics , Betacoronavirus/immunology , /metabolism , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Genome, Viral , Host-Pathogen Interactions , Humans , Immune Evasion , Protein Interaction Maps , /immunology , Viral Matrix Proteins/genetics , Viral Matrix Proteins/immunology , Virus Internalization , Virus Replication
4.
Clin Microbiol Infect ; 26(8): 1094.e1-1094.e5, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1023515

ABSTRACT

OBJECTIVES: To detect possible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA contamination of inanimate surfaces in areas at high risk of aerosol formation by patients with coronavirus disease 2019 (COVID-19). METHODS: Sampling was performed in the emergency unit and the sub-intensive care ward. SARS-CoV-2 RNA was extracted from swabbed surfaces and objects and subjected to real-time RT-PCR targeting RNA-dependent RNA polymerase and E genes. Virus isolation from positive samples was attempted in vitro on Vero E6 cells. RESULTS: Twenty-six samples were collected and only two were positive for low-level SARS-CoV-2 RNA, both collected on the external surface of continuous positive airway pressure helmets. All transport media were inoculated onto susceptible cells, but none induced a cytopathic effect on day 7 of culture. CONCLUSIONS: Even though daily contact with inanimate surfaces and patient fomites in contaminated areas may be a medium of infection, our data obtained in real-life conditions suggest that it might be less extensive than hitherto recognized.


Subject(s)
Betacoronavirus/growth & development , Fomites/virology , Viral Envelope Proteins/genetics , Animals , Betacoronavirus/genetics , Chlorocebus aethiops , Equipment Contamination , Humans , Intensive Care Units , Microbial Viability , Reverse Transcriptase Polymerase Chain Reaction , Vero Cells , Viral Proteins/genetics
5.
PLoS One ; 15(10): e0241405, 2020.
Article in English | MEDLINE | ID: covidwho-1024408

ABSTRACT

BACKGROUND: The first cases of COVID-19 caused by the SARS-CoV-2 virus were reported in China in December 2019. The disease has since spread globally. Many countries have instated measures to slow the spread of the virus. Information about the spread of the virus in a country can inform the gradual reopening of a country and help to avoid a second wave of infections. Our study focuses on Denmark, which is opening up when this study is performed (end-May 2020) after a lockdown in mid-March. METHODS: We perform a phylogenetic analysis of 742 publicly available Danish SARS-CoV-2 genome sequences and put them into context using sequences from other countries. RESULTS: Our findings are consistent with several introductions of the virus to Denmark from independent sources. We identify several chains of mutations that occurred in Denmark. In at least one case we find evidence that the virus spread from Denmark to other countries. A number of the mutations found in Denmark are non-synonymous, and in general there is a considerable variety of strains. The proportions of the most common haplotypes remain stable after lockdown. CONCLUSION: Employing phylogenetic methods on Danish genome sequences of SARS-CoV-2, we exemplify how genetic data can be used to trace the introduction of a virus to a country. This provides alternative means for verifying existing assumptions. For example, our analysis supports the hypothesis that the virus was brought to Denmark by skiers returning from Ischgl. On the other hand, we identify transmission routes which suggest that Denmark was part of a network of countries among which the virus was being transmitted. This challenges the common narrative that Denmark only got infected from abroad. Our analysis concerning the ratio of haplotypes does not indicate that the major haplotypes appearing in Denmark have a different degree of virality.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/transmission , Genome, Viral , Mutation , Pneumonia, Viral/transmission , Coronavirus Infections/epidemiology , Denmark/epidemiology , Haplotypes , Humans , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology
6.
PLoS One ; 15(10): e0241163, 2020.
Article in English | MEDLINE | ID: covidwho-1024405

ABSTRACT

The events of the recent SARS-CoV-2 epidemics have shown the importance of social factors, especially given the large number of asymptomatic cases that effectively spread the virus, which can cause a medical emergency to very susceptible individuals. Besides, the SARS-CoV-2 virus survives for several hours on different surfaces, where a new host can contract it with a delay. These passive modes of infection transmission remain an unexplored area for traditional mean-field epidemic models. Here, we design an agent-based model for simulations of infection transmission in an open system driven by the dynamics of social activity; the model takes into account the personal characteristics of individuals, as well as the survival time of the virus and its potential mutations. A growing bipartite graph embodies this biosocial process, consisting of active carriers (host) nodes that produce viral nodes during their infectious period. With its directed edges passing through viral nodes between two successive hosts, this graph contains complete information about the routes leading to each infected individual. We determine temporal fluctuations of the number of exposed and the number of infected individuals, the number of active carriers and active viruses at hourly resolution. The simulated processes underpin the latent infection transmissions, contributing significantly to the spread of the virus within a large time window. More precisely, being brought by social dynamics and exposed to the currently existing infection, an individual passes through the infectious state until eventually spontaneously recovers or otherwise is moves to a controlled hospital environment. Our results reveal complex feedback mechanisms that shape the dependence of the infection curve on the intensity of social dynamics and other sociobiological factors. In particular, the results show how the lockdown effectively reduces the spread of infection and how it increases again after the lockdown is removed. Furthermore, a reduced level of social activity but prolonged exposure of susceptible individuals have adverse effects. On the other hand, virus mutations that can gradually reduce the transmission rate by hopping to each new host along the infection path can significantly reduce the extent of the infection, but can not stop the spreading without additional social strategies. Our stochastic processes, based on graphs at the interface of biology and social dynamics, provide a new mathematical framework for simulations of various epidemic control strategies with high temporal resolution and virus traceability.


Subject(s)
Asymptomatic Infections , Betacoronavirus/genetics , Coronavirus Infections/transmission , Models, Statistical , Pneumonia, Viral/transmission , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Disease Susceptibility , Humans , Interpersonal Relations , Mutation , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/virology , Quarantine/methods , Stochastic Processes , Time Factors
7.
Clin Chem ; 66(4): 549-555, 2020 04 01.
Article in English | MEDLINE | ID: covidwho-1024088

ABSTRACT

BACKGROUND: A novel coronavirus of zoonotic origin (2019-nCoV) has recently been identified in patients with acute respiratory disease. This virus is genetically similar to SARS coronavirus and bat SARS-like coronaviruses. The outbreak was initially detected in Wuhan, a major city of China, but has subsequently been detected in other provinces of China. Travel-associated cases have also been reported in a few other countries. Outbreaks in health care workers indicate human-to-human transmission. Molecular tests for rapid detection of this virus are urgently needed for early identification of infected patients. METHODS: We developed two 1-step quantitative real-time reverse-transcription PCR assays to detect two different regions (ORF1b and N) of the viral genome. The primer and probe sets were designed to react with this novel coronavirus and its closely related viruses, such as SARS coronavirus. These assays were evaluated using a panel of positive and negative controls. In addition, respiratory specimens from two 2019-nCoV-infected patients were tested. RESULTS: Using RNA extracted from cells infected by SARS coronavirus as a positive control, these assays were shown to have a dynamic range of at least seven orders of magnitude (2x10-4-2000 TCID50/reaction). Using DNA plasmids as positive standards, the detection limits of these assays were found to be below 10 copies per reaction. All negative control samples were negative in the assays. Samples from two 2019-nCoV-infected patients were positive in the tests. CONCLUSIONS: The established assays can achieve a rapid detection of 2019n-CoV in human samples, thereby allowing early identification of patients.


Subject(s)
Betacoronavirus/genetics , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Disease Outbreaks , Humans , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , RNA, Viral/genetics , RNA, Viral/isolation & purification , Real-Time Polymerase Chain Reaction
9.
Nat Biotechnol ; 38(10): 1164-1167, 2020 10.
Article in English | MEDLINE | ID: covidwho-1023956

ABSTRACT

We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA concentrations in primary sewage sludge in the New Haven, Connecticut, USA, metropolitan area during the Coronavirus Disease 2019 (COVID-19) outbreak in Spring 2020. SARS-CoV-2 RNA was detected throughout the more than 10-week study and, when adjusted for time lags, tracked the rise and fall of cases seen in SARS-CoV-2 clinical test results and local COVID-19 hospital admissions. Relative to these indicators, SARS-CoV-2 RNA concentrations in sludge were 0-2 d ahead of SARS-CoV-2 positive test results by date of specimen collection, 0-2 d ahead of the percentage of positive tests by date of specimen collection, 1-4 d ahead of local hospital admissions and 6-8 d ahead of SARS-CoV-2 positive test results by reporting date. Our data show the utility of viral RNA monitoring in municipal wastewater for SARS-CoV-2 infection surveillance at a population-wide level. In communities facing a delay between specimen collection and the reporting of test results, immediate wastewater results can provide considerable advance notice of infection dynamics.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , RNA, Viral/analysis , Waste Water/virology , Wastewater-Based Epidemiological Monitoring , Betacoronavirus/genetics , Biotechnology , Connecticut/epidemiology , Humans , Prevalence , RNA, Viral/genetics , Sewage/virology , Time Factors
11.
Nat Biotechnol ; 38(9): 1073-1078, 2020 09.
Article in English | MEDLINE | ID: covidwho-1023948

ABSTRACT

A robust serological test to detect neutralizing antibodies to SARS-CoV-2 is urgently needed to determine not only the infection rate, herd immunity and predicted humoral protection, but also vaccine efficacy during clinical trials and after large-scale vaccination. The current gold standard is the conventional virus neutralization test requiring live pathogen and a biosafety level 3 laboratory. Here, we report a SARS-CoV-2 surrogate virus neutralization test that detects total immunodominant neutralizing antibodies targeting the viral spike (S) protein receptor-binding domain in an isotype- and species-independent manner. Our simple and rapid test is based on antibody-mediated blockage of the interaction between the angiotensin-converting enzyme 2 (ACE2) receptor protein and the receptor-binding domain. The test, which has been validated with two cohorts of patients with COVID-19 in two different countries, achieves 99.93% specificity and 95-100% sensitivity, and differentiates antibody responses to several human coronaviruses. The surrogate virus neutralization test does not require biosafety level 3 containment, making it broadly accessible to the wider community for both research and clinical applications.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/genetics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Spike Glycoprotein, Coronavirus/genetics , Antibodies/immunology , Antibodies/pharmacology , Betacoronavirus/genetics , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Humans , Neutralization Tests , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Protein Interaction Domains and Motifs/genetics , Spike Glycoprotein, Coronavirus/chemistry
12.
Diagnosis (Berl) ; 7(4): 357-363, 2020 Nov 18.
Article in English | MEDLINE | ID: covidwho-1021710

ABSTRACT

Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently recognized as a systemic disorder inducing a prothrombotic state. The molecular mechanisms underlying the hypercoagulable state seen in patients with COVID-19 is still incompletely understood, although it presumably involves the close link between inflammatory and hemostatic systems. The laboratory coagulation monitoring of severely ill COVID-19 patients is mandatory to identify those patients at increased thrombotic risk and to modulate thromboprophylaxis accordingly. In this review, we summarize the current understanding on the pathogenesis, epidemiology, clinical and laboratory features and management of coagulopathy associated with COVID-19.


Subject(s)
Betacoronavirus/genetics , Blood Coagulation Disorders/etiology , Coronavirus Infections/diagnosis , Pneumonia, Viral/complications , Anticoagulants/therapeutic use , Blood Coagulation Disorders/prevention & control , Blood Coagulation Disorders/virology , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Humans , Inflammation/complications , Inflammation/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Severity of Illness Index , Thromboembolism/drug therapy , Thromboembolism/etiology , Thromboembolism/prevention & control , Thrombosis/epidemiology , Thrombosis/prevention & control
15.
Trials ; 21(1): 939, 2020 Nov 23.
Article in English | MEDLINE | ID: covidwho-992534

ABSTRACT

BACKGROUND: Pharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still lacking. We have identified IFNß-1a as the most promising drug to be repurposed for COVID-19. The rationale relies on the evidence of IFNß anti-viral activity in vitro against SARS-CoV-2 and animal models resembling SARS-CoV-2 infection and on a recent clinical trial where IFNß was indicated as the key component of a successful therapeutic combination. METHODS: This is a randomized, controlled, open-label, monocentric, phase II trial (INTERCOP trial). One hundred twenty-six patients with positive swab detection of SARS-CoV-2, radiological signs of pneumonia, and mild-to-moderate disease will be randomized 2:1 to IFNß-1a in addition to standard of care vs standard of care alone. No other anti-viral drugs will be used as part of the regimens, both in the control and the intervention arms. IFNß-1a will be administered subcutaneously at the dose of 44 mcg (equivalent to 12 million international units) three times per week, at least 48 h apart, for a total of 2 weeks. The primary outcome is the time to negative conversion of SARS-CoV-2 nasopharyngeal swabs. Secondary outcomes include improvement or worsening in a clinical severity score measured on a 7-point ordinal scale (including transfer to intensive care unit and death), oxygen- and ventilator-free days, mortality, changes in pulmonary computed tomography severity score, hospital stay duration, reduction of viral load measured on nasopharyngeal swabs, number of serious adverse events, and changes in biochemical markers of organ dysfunction. Exploratory outcomes include blood cell counts, cytokine and inflammatory profile, peripheral mRNA expression profiles of interferon-stimulated genes, and antibodies to SARS-CoV-2 and to IFNß-1a. INTERCOP is the first study to specifically investigate the clinical benefits of IFNß-1a in COVID-19 patients. DISCUSSION: Potential implications of this trial are multifaceted: should the primary outcome be fulfilled and the treatment be safe, one may envisage that IFNß-1a be used to reduce the infectivity of patients with mild-to moderate disease. In case IFNß-1a reduced the duration of hospital stay and/or ameliorated the clinical status, it may become a cornerstone of COVID-19 treatment. TRIAL REGISTRATION: EudraCT 2020-002458-25. Registered on May 11, 2020 ClinicalTrials.gov Identifier: NCT04449380.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Interferon beta-1a/therapeutic use , Pneumonia, Viral/drug therapy , Adult , Antiviral Agents/administration & dosage , Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Data Management , Female , Humans , Injections, Subcutaneous , Interferon beta-1a/administration & dosage , Italy/epidemiology , Length of Stay/statistics & numerical data , Male , Mortality/trends , Oxygen/administration & dosage , Oxygen/therapeutic use , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Treatment Outcome , Viral Load/drug effects
17.
EBioMedicine ; 61: 103069, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-983306

ABSTRACT

BACKGROUND: Italy was the first western country to experience a large Coronavirus Disease 2019 (COVID-19) outbreak and the province of Bergamo experienced one of the deadliest COVID-19 outbreaks in the world. Following the peak of the epidemic in mid-March, the curve has slowly fallen thanks to the strict lockdown imposed by the Italian government on 9th March 2020. METHODS: We performed a cross-sectional study to assess the prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in 423 workers in Bergamo province who returned to the workplace after the end of the Italian lockdown on 5th May 2020. To this end, we performed an enzyme-linked immunosorbent assay (ELISA) to detect the humoral response against SARS-CoV-2 and a nasopharyngeal swab to assess the presence of SARS-CoV-2 RNA by real-time reverse transcription polymerase chain reaction (rRT-PCR). As a secondary aim of the study, we validated a lateral flow immunochromatography assay (LFIA) for the detection of anti-SARS-CoV-2 antibodies. FINDINGS: ELISA identified 38.5% positive subjects, of whom 51.5% were positive for both IgG and IgM, 47.3% were positive only for IgG, but only 1.2% were positive for IgM alone. Only 23 (5.4%) participants tested positive for SARS-CoV-2 by rRT-PCR, although with high cycle thresholds (between 34 and 39), indicating a very low residual viral load that was not able to infect cultured cells. All these rRT-PCR positive subjects had already experienced seroconversion. When the ELISA was used as the comparator, the estimated specificity and sensitivity of the rapid LFIA for IgG were 98% and 92%, respectively. INTERPRETATION: the prevalence of SARS-CoV-2 infection in the province of Bergamo reached 38.5%, significantly higher than has been reported for most other regions worldwide. Few nasopharyngeal swabs tested positive in fully recovered subjects, though with a very low SARS-CoV-2 viral load, with implications for infectivity and discharge policies for positive individuals in the post-pandemic period. The rapid LFIA used in this study is a valuable tool for rapid serologic surveillance of COVID-19 for population studies. FUNDING: The study was supported by Regione Lombardia, Milano Serravalle - Milano Tangenziali S.p.A., Brembo S.p.A, and by MEI System.


Subject(s)
Antibodies, Viral/blood , Betacoronavirus/genetics , Betacoronavirus/immunology , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , RNA, Viral/metabolism , Adult , Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Italy/epidemiology , Male , Middle Aged , Nasopharynx/virology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Viral Load
18.
Viruses ; 12(11)2020 10 22.
Article in English | MEDLINE | ID: covidwho-983185

ABSTRACT

The origin of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virus causing the COVID-19 pandemic has not yet been fully determined. Despite the consensus about the SARS-CoV-2 origin from bat CoV RaTG13, discrepancy to host tropism to other human Coronaviruses exist. SARS-CoV-2 also possesses some differences in its S protein receptor-binding domain, glycan-binding N-terminal domain and the surface of the sialic acid-binding domain. Despite similarities based on cryo-EM and biochemical studies, the SARS-CoV-2 shows higher stability and binding affinity to the ACE2 receptor. The SARS-CoV-2 does not appear to present a mutational "hot spot" as only the D614G mutation has been identified from clinical isolates. As laboratory manipulation is highly unlikely for the origin of SARS-CoV-2, the current possibilities comprise either natural selection in animal host before zoonotic transfer or natural selection in humans following zoonotic transfer. In the former case, despite SARS-CoV-2 and bat RaTG13 showing 96% identity some pangolin Coronaviruses exhibit very high similarity to particularly the receptor-binding domain of SARS-CoV-2. In the latter case, it can be hypothesized that the SARS-CoV-2 genome has adapted during human-to-human transmission and based on available data, the isolated SARS-CoV-2 genomes derive from a common origin. Before the origin of SARS-CoV-2 can be confirmed additional research is required.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/transmission , Coronavirus Infections/virology , Genome, Viral , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Animals , Coronavirus Infections/epidemiology , Genome, Viral/genetics , Humans , Mutation , Pandemics , Pneumonia, Viral/epidemiology , Protein Domains , Selection, Genetic , Viral Proteins/chemistry , Viral Proteins/genetics , Zoonoses/transmission , Zoonoses/virology
19.
Viruses ; 12(10)2020 10 09.
Article in English | MEDLINE | ID: covidwho-983003

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for the ongoing coronavirus disease (COVID-19) pandemic, is frequently shed in faeces during infection, and viral RNA has recently been detected in sewage in some countries. We have investigated the presence of SARS-CoV-2 RNA in wastewater samples from South-East England between 14th January and 12th May 2020. A novel nested RT-PCR approach targeting five different regions of the viral genome improved the sensitivity of RT-qPCR assays and generated nucleotide sequences at sites with known sequence polymorphisms among SARS-CoV-2 isolates. We were able to detect co-circulating virus variants, some specifically prevalent in England, and to identify changes in viral RNA sequences with time consistent with the recently reported increasing global dominance of Spike protein G614 pandemic variant. Low levels of viral RNA were detected in a sample from 11th February, 3 days before the first case was reported in the sewage plant catchment area. SARS-CoV-2 RNA concentration increased in March and April, and a sharp reduction was observed in May, showing the effects of lockdown measures. We conclude that viral RNA sequences found in sewage closely resemble those from clinical samples and that environmental surveillance can be used to monitor SARS-CoV-2 transmission, tracing virus variants and detecting virus importations.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Sewage/virology , Betacoronavirus/isolation & purification , England/epidemiology , Environmental Monitoring , Genetic Variation , Genome, Viral/genetics , Humans , Pandemics , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Sequence Analysis, DNA , Waste Water/virology
20.
Zool Res ; 41(6): 621-631, 2020 11 18.
Article in English | MEDLINE | ID: covidwho-982982

ABSTRACT

Understanding the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and clarifying antiviral immunity in hosts are critical aspects for the development of vaccines and antivirals. Mice are frequently used to generate animal models of infectious diseases due to their convenience and ability to undergo genetic manipulation. However, normal adult mice are not susceptible to SARS-CoV-2. Here, we developed a viral receptor (human angiotensin-converting enzyme 2, hACE2) pulmonary transfection mouse model to establish SARS-CoV-2 infection rapidly in the mouse lung. Based on the model, the virus successfully infected the mouse lung 2 days after transfection. Viral RNA/protein, innate immune cell infiltration, inflammatory cytokine expression, and pathological changes in the infected lungs were observed after infection. Further studies indicated that neutrophils were the first and most abundant leukocytes to infiltrate the infected lungs after viral infection. In addition, using infected CXCL5-knockout mice, chemokine CXCL5 was responsible for neutrophil recruitment. CXCL5 knockout decreased lung inflammation without diminishing viral clearance, suggesting a potential target for controlling pneumonia.


Subject(s)
Betacoronavirus/immunology , Chemokine CXCL5/immunology , Coronavirus Infections/immunology , Immunity, Innate/immunology , Neutrophils/immunology , Peptidyl-Dipeptidase A/immunology , Pneumonia, Viral/immunology , Animals , Betacoronavirus/genetics , Betacoronavirus/physiology , Cell Line , Chemokine CXCL5/genetics , Chemokine CXCL5/metabolism , Coronavirus Infections/genetics , Coronavirus Infections/virology , Cytokines/immunology , Cytokines/metabolism , Disease Models, Animal , Humans , Male , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Neutrophils/metabolism , Neutrophils/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/genetics , Pneumonia, Viral/virology
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