Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 410
Filter
Add filters

Year range
1.
Emerg Microbes Infect ; 9(1): 1567-1579, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-707709

ABSTRACT

Diverse SARS-like coronaviruses (SL-CoVs) have been identified from bats and other animal species. Like SARS-CoV, some bat SL-CoVs, such as WIV1, also use angiotensin converting enzyme 2 (ACE2) from human and bat as entry receptor. However, whether these viruses can also use the ACE2 of other animal species as their receptor remains to be determined. We report herein that WIV1 has a broader tropism to ACE2 orthologs than SARS-CoV isolate Tor2. Among the 9 ACE2 orthologs examined, human ACE2 exhibited the highest efficiency to mediate the infection of WIV1 pseudotyped virus. Our findings thus imply that WIV1 has the potential to infect a wide range of wild animals and may directly jump to humans. We also showed that cell entry of WIV1 could be restricted by interferon-induced transmembrane proteins (IFITMs). However, WIV1 could exploit the airway protease TMPRSS2 to partially evade the IFITM3 restriction. Interestingly, we also found that amphotericin B could enhance the infectious entry of SARS-CoVs and SL-CoVs by evading IFITM3-mediated restriction. Collectively, our findings further underscore the risk of exposure to animal SL-CoVs and highlight the vulnerability of patients who take amphotericin B to infection by SL-CoVs, including the most recently emerging (SARS-CoV-2).


Subject(s)
Betacoronavirus/physiology , Chiroptera/virology , Membrane Proteins/metabolism , Peptidyl-Dipeptidase A/metabolism , RNA-Binding Proteins/metabolism , Receptors, Virus/metabolism , Serine Endopeptidases/metabolism , Virus Internalization , Animals , Betacoronavirus/classification , HEK293 Cells , Humans , Rats , SARS Virus/physiology , Viverridae
2.
Am J Physiol Heart Circ Physiol ; 318(5): H1084-H1090, 2020 05 01.
Article in English | MEDLINE | ID: covidwho-707207

ABSTRACT

The novel SARS coronavirus SARS-CoV-2 pandemic may be particularly deleterious to patients with underlying cardiovascular disease (CVD). The mechanism for SARS-CoV-2 infection is the requisite binding of the virus to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. Recognition that ACE2 is the coreceptor for the coronavirus has prompted new therapeutic approaches to block the enzyme or reduce its expression to prevent the cellular entry and SARS-CoV-2 infection in tissues that express ACE2 including lung, heart, kidney, brain, and gut. ACE2, however, is a key enzymatic component of the renin-angiotensin-aldosterone system (RAAS); ACE2 degrades ANG II, a peptide with multiple actions that promote CVD, and generates Ang-(1-7), which antagonizes the effects of ANG II. Moreover, experimental evidence suggests that RAAS blockade by ACE inhibitors, ANG II type 1 receptor antagonists, and mineralocorticoid antagonists, as well as statins, enhance ACE2 which, in part, contributes to the benefit of these regimens. In lieu of the fact that many older patients with hypertension or other CVDs are routinely treated with RAAS blockers and statins, new clinical concerns have developed regarding whether these patients are at greater risk for SARS-CoV-2 infection, whether RAAS and statin therapy should be discontinued, and the potential consequences of RAAS blockade to COVID-19-related pathologies such as acute and chronic respiratory disease. The current perspective critically examines the evidence for ACE2 regulation by RAAS blockade and statins, the cardiovascular benefits of ACE2, and whether ACE2 blockade is a viable approach to attenuate COVID-19.


Subject(s)
Betacoronavirus/physiology , Cardiovascular Diseases/enzymology , Cardiovascular Diseases/virology , Coronavirus Infections/enzymology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/enzymology , Animals , Betacoronavirus/metabolism , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Humans , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Rats , Rats, Inbred Lew , Virus Internalization
3.
Curr Probl Cardiol ; 45(8): 100618, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-694853

ABSTRACT

Since the outbreak and rapid spread of COVID-19 starting late December 2019, it has been apparent that disease prognosis has largely been influenced by multiorgan involvement. Comorbidities such as cardiovascular diseases have been the most common risk factors for severity and mortality. The hyperinflammatory response of the body, coupled with the plausible direct effects of severe acute respiratory syndrome on body-wide organs via angiotensin-converting enzyme 2, has been associated with complications of the disease. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock, and multiorgan failure have precipitated death. Acknowledging the comorbidities and potential organ injuries throughout the course of COVID-19 is therefore crucial in the clinical management of patients. This paper aims to add onto the ever-emerging landscape of medical knowledge on COVID-19, encapsulating its multiorgan impact.


Subject(s)
Cardiovascular Diseases/epidemiology , Coronavirus Infections , Multiple Organ Failure , Pandemics , Pneumonia, Viral , Betacoronavirus/physiology , Comorbidity , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Humans , Multiple Organ Failure/etiology , Multiple Organ Failure/immunology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Risk Factors
5.
J Virol ; 94(15)2020 07 16.
Article in English | MEDLINE | ID: covidwho-690841

ABSTRACT

Currently, there are four seasonal coronaviruses associated with relatively mild respiratory tract disease in humans. However, there is also a plethora of animal coronaviruses which have the potential to cross the species border. This regularly results in the emergence of new viruses in humans. In 2002, severe acute respiratory syndrome coronavirus (SARS-CoV) emerged and rapidly disappeared in May 2003. In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a possible threat to humans, but its pandemic potential so far is minimal, as human-to-human transmission is ineffective. The end of 2019 brought us information about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emergence, and the virus rapidly spread in 2020, causing an unprecedented pandemic. At present, studies on the virus are carried out using a surrogate system based on the immortalized simian Vero E6 cell line. This model is convenient for diagnostics, but it has serious limitations and does not allow for understanding of the biology and evolution of the virus. Here, we show that fully differentiated human airway epithelium cultures constitute an excellent model to study infection with the novel human coronavirus SARS-CoV-2. We observed efficient replication of the virus in the tissue, with maximal replication at 2 days postinfection. The virus replicated in ciliated cells and was released apically.IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged by the end of 2019 and rapidly spread in 2020. At present, it is of utmost importance to understand the biology of the virus, rapidly assess the treatment potential of existing drugs, and develop new active compounds. While some animal models for such studies are under development, most of the research is carried out in Vero E6 cells. Here, we propose fully differentiated human airway epithelium cultures as a model for studies on SARS-CoV-2.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/virology , Pneumonia, Viral/virology , Respiratory Mucosa/virology , Severe Acute Respiratory Syndrome/virology , Virus Replication , Animals , Cell Line , Cells, Cultured , Chlorocebus aethiops , Humans , Pandemics , Vero Cells
6.
Elife ; 92020 07 30.
Article in English | MEDLINE | ID: covidwho-690669

ABSTRACT

The COVID-19 pandemic caused by the SARS-CoV-2 has recently emerged as a serious jolt to human life and economy. Initial knowledge established pulmonary complications as the chief symptom, however, the neurological aspect of the disease is also becoming increasingly evident. Emerging reports of encephalopathies and similar ailments with the detection of the virus in the CSF has elicited an urgent need for investigating the possibility of neuroinvasiveness of the virus, which cannot be ruled out given the expression of low levels of ACE2 receptors in the brain. Sensory impairments of the olfactory and gustatory systems have also been reported in a large proportion of the cases, indicating the involvement of the peripheral nervous system. Hence, the possibility of neurological damage caused by the virus demands immediate attention and investigation of the mechanisms involved, so as to customize the treatment of patients presenting with neurological complications.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Nervous System Diseases/etiology , Pneumonia, Viral/complications , Ageusia/etiology , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , Brain/metabolism , Brain/virology , Cerebrovascular Disorders/etiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Encephalitis, Viral/etiology , Host Microbial Interactions , Humans , Models, Neurological , Nervous System Diseases/physiopathology , Nervous System Diseases/virology , Olfaction Disorders/etiology , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Receptors, Virus/metabolism
8.
Virol J ; 17(1): 117, 2020 07 29.
Article in English | MEDLINE | ID: covidwho-684739

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has spread rapidly across the world and become an international public health emergency. Both SARS-CoV-2 and SARS-CoV belong to subfamily Coronavirinae in the family Coronaviridae of the order Nidovirales and they are classified as the SARS-like species while belong to different cluster. Besides, viral structure, epidemiology characteristics and pathological characteristics are also different. We present a comprehensive survey of the latest coronavirus-SARS-CoV-2-from investigating its origin and evolution alongside SARS-CoV. Meanwhile, pathogenesis, cardiovascular disease in COVID-19 patients, myocardial injury and venous thromboembolism induced by SARS-CoV-2 as well as the treatment methods are summarized in this review.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Antiviral Agents/therapeutic use , Asymptomatic Infections , Betacoronavirus/chemistry , Betacoronavirus/classification , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , Comorbidity , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/therapy , Disease Susceptibility , Evolution, Molecular , Genome, Viral , Humans , Immunization, Passive , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/therapy , Receptors, Virus/metabolism , SARS Virus/chemistry , SARS Virus/classification , SARS Virus/pathogenicity , SARS Virus/physiology , Viral Proteins/chemistry
9.
Front Immunol ; 11: 1409, 2020.
Article in English | MEDLINE | ID: covidwho-680017

ABSTRACT

As the world is severely affected by COVID-19 pandemic, the use of chloroquine and hydroxychloroquine in prevention or for the treatment of patients is allowed in multiple countries but remained at the center of much controversy in recent days. This review describes the properties of chloroquine and hydroxychloroquine, and highlights not only their anti-viral effects but also their important immune-modulatory properties and their well-known use in autoimmune diseases, including systemic lupus and arthritis. Chloroquine appears to inhibit in vitro SARS virus' replication and to interfere with SARS-CoV2 receptor (ACE2). Chloroquine and hydroxychloroquine impede lysosomal activity and autophagy, leading to a decrease of antigen processing and presentation. They are also known to interfere with endosomal Toll-like receptors signaling and cytosolic sensors of nucleic acids, which result in a decreased cellular activation and thereby a lower type I interferons and inflammatory cytokine secretion. Given the antiviral and anti-inflammatory properties of chloroquine and hydroxychloroquine, there is a rational to use them against SARS-CoV2 infection. However, the anti-interferon properties of these molecules might be detrimental, and impaired host immune responses against the virus. This duality could explain the discrepancy with the recently published studies on CQ/HCQ treatment efficacy in COVID-19 patients. Moreover, although these treatments could be an interesting potential strategy to limit progression toward uncontrolled inflammation, they do not appear per se sufficiently potent to control the whole inflammatory process in COVID-19, and more targeted and/or potent therapies should be required at least in add-on.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/physiology , Hydroxychloroquine/therapeutic use , Pandemics , Virus Replication/drug effects , Antigen Presentation , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Humans , Lysosomes/immunology , Lysosomes/virology , Peptidyl-Dipeptidase A/immunology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Toll-Like Receptors/immunology , Virus Replication/immunology
10.
Int J Mol Med ; 46(2): 467-488, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-678269

ABSTRACT

The major impact produced by the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) focused many researchers attention to find treatments that can suppress transmission or ameliorate the disease. Despite the very fast and large flow of scientific data on possible treatment solutions, none have yet demonstrated unequivocal clinical utility against coronavirus disease 2019 (COVID­19). This work represents an exhaustive and critical review of all available data on potential treatments for COVID­19, highlighting their mechanistic characteristics and the strategy development rationale. Drug repurposing, also known as drug repositioning, and target based methods are the most used strategies to advance therapeutic solutions into clinical practice. Current in silico, in vitro and in vivo evidence regarding proposed treatments are summarized providing strong support for future research efforts.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Drug Repositioning , Pneumonia, Viral/drug therapy , Virus Internalization/drug effects , Angiotensin II Type 1 Receptor Blockers/classification , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , Bromhexine/pharmacology , Bromhexine/therapeutic use , Chlorpromazine/pharmacology , Chlorpromazine/therapeutic use , Clinical Trials as Topic/methods , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Diminazene/pharmacology , Diminazene/therapeutic use , Drug Repositioning/methods , Drug Repositioning/standards , Drug Repositioning/trends , Gabexate/analogs & derivatives , Gabexate/pharmacology , Gabexate/therapeutic use , Humans , Pandemics , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Peptidyl-Dipeptidase A/therapeutic use , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Receptor, Angiotensin, Type 1/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/therapeutic use , Signal Transduction/drug effects
11.
Infect Dis Poverty ; 9(1): 104, 2020 Jul 23.
Article in English | MEDLINE | ID: covidwho-672011

ABSTRACT

From December 25, 2019 to January 31, 2020, 33 cases of the coronavirus disease 2019 (COVID-19) were identified in the Department of Respiratory and Critical Care Medicine of Zhongnan Hospital of Wuhan University, China, yet none of the affiliated HCWs was infected. Here we analyzed the infection control measures used in three different departments in the Zhongnan Hospital of Wuhan University and correlated the measures with the corresponding infection data of HCWs affiliated with these departments. We found that three infection control measures, namely the isolation of the presumed positive patients, the use of facemasks and intensified hand hygiene play important roles in preventing nosocomial transmission of COVID-19.


Subject(s)
Coronavirus Infections/prevention & control , Cross Infection/prevention & control , Hand Hygiene/statistics & numerical data , Health Personnel/statistics & numerical data , Masks/statistics & numerical data , Pandemics/prevention & control , Patient Isolation/statistics & numerical data , Pneumonia, Viral/prevention & control , Adult , Aged , Betacoronavirus/physiology , China , Coronavirus Infections/transmission , Cross Infection/transmission , Female , Hospitals, University , Humans , Male , Middle Aged , Pneumonia, Viral/transmission , Young Adult
12.
Rev Int Androl ; 18(3): 117-123, 2020.
Article in Spanish | MEDLINE | ID: covidwho-664119

ABSTRACT

OBJECTIVE: The main objective of this revision is to summarize the current existing evidence of the potential adverse effects of SARS-CoV-2 on the male reproductive system and provide the recommendations of the Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA) concerning the implications of COVID-19 infection in the management of male infertilty patients and testicular endocrine dysfunction. METHODS: A comprehensive systematic literature search of the databases of PubMed, Web of Science, Embase, Medline, Cochrane and MedRxiv, was carried out. RESULTS: The presence of orchitis as a potential complication of the infection by SARS-CoV-2 has not yet been confirmed. One study reported that 19% of males with COVID-19 infection had scrotal symptoms suggestive of viral orchitis which could not be confirmed. It is possible that the virus, rather than infecting the testes directly, may induce a secondary autoimmune response leading to autoimmune orchitis. COVID-19 has been associated with coagulation disorders and thus the orchitis could be the result of segmental vasculitis. Existing data concerning the presence of the virus in semen are contradictory. Only one study reported the presence of RNA in 15.8% of patients with COVID-19. However, the presence of nucleic acid or antigen in semen is not synonyms of viral replication capacity and infectivity. It has been reported an increase in serum levels of LH in males with COVID-19 and a significant reduction in the T/LH and FSH/LH ratios, consistent with subclinical hypogonadism. CONCLUSIONS: The findings of recent reports related to the potential effects of COVID-19 infection on the male reproductive system are based on poorly designed, small sample size studies that provide inconclusive, contradictory results. Since there still exists a theoretical possibility of testicular damage and male infertilty as a result of the infection by COVID-19, males of reproductive age should be evaluated for gonadal function and semen analysis. With regard to the sexual transmission of the virus, there is not sufficient evidence to recommend asymptomatic couples to abstein from having sex in order to protect themselves from being infected by the virus. Additional studies are needed to understand the long-term effects of SARS-CoV-2 on male reproductive function, including male fertility potential and endocrine testicular function.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Pandemics , Pneumonia, Viral/complications , Reproductive Health , Sexual Health , Adult , Betacoronavirus/isolation & purification , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , Follicle Stimulating Hormone/blood , Humans , Hypogonadism/blood , Hypogonadism/etiology , Immunoglobulin G/analysis , Leukocytes , Luteinizing Hormone/blood , Male , Orchitis/etiology , Orchitis/virology , Prostate/virology , RNA, Viral/analysis , Reverse Transcriptase Polymerase Chain Reaction , Semen/virology , Semen Preservation , Spain , Testis/immunology , Testis/pathology , Testis/virology , Testosterone/blood , Vasculitis/etiology , Young Adult
13.
J Virol ; 94(15)2020 07 16.
Article in English | MEDLINE | ID: covidwho-661225

ABSTRACT

The emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in a pandemic. Here, we used X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of SARS-CoV-2. Comparing the interaction sites of ACE2 proteins known to serve or not serve as receptors allows the definition of residues important for binding. From the 20 amino acids in ACE2 that contact S, up to 7 can be replaced and ACE2 can still function as the SARS-CoV-2 receptor. These variable amino acids are clustered at certain positions, mostly at the periphery of the binding site, while changes of the invariable residues prevent S binding or infection of the respective animal. Some ACE2 proteins even tolerate the loss or acquisition of N-glycosylation sites located near the S interface. Of note, pigs and dogs, which are not infected or are not effectively infected and have only a few changes in the binding site, exhibit relatively low levels of ACE2 in the respiratory tract. Comparison of the RBD of S of SARS-CoV-2 with that from bat coronavirus strain RaTG13 (Bat-CoV-RaTG13) and pangolin coronavirus (Pangolin-CoV) strain hCoV-19/pangolin/Guangdong/1/2019 revealed that the latter contains only one substitution, whereas Bat-CoV-RaTG13 exhibits five. However, ACE2 of pangolin exhibits seven changes relative to human ACE2, and a similar number of substitutions is present in ACE2 of bats, raccoon dogs, and civets, suggesting that SARS-CoV-2 may not be especially adapted to ACE2 of any of its putative intermediate hosts. These analyses provide new insight into the receptor usage and animal source/origin of SARS-CoV-2.IMPORTANCE SARS-CoV-2 is threatening people worldwide, and there are no drugs or vaccines available to mitigate its spread. The origin of the virus is still unclear, and whether pets and livestock can be infected and transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis provides a framework for the prediction of potential hosts of SARS-CoV-2. We found that ACE2 from species known to support SARS-CoV-2 infection tolerate many amino acid changes, indicating that the species barrier might be low. Exceptions are dogs and especially pigs, which revealed relatively low ACE2 expression levels in the respiratory tract. Monitoring of animals is necessary to prevent the generation of a new coronavirus reservoir. Finally, our analysis also showed that SARS-CoV-2 may not be specifically adapted to any of its putative intermediate hosts.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/virology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/virology , Spike Glycoprotein, Coronavirus/metabolism , Virus Attachment , Animals , Animals, Domestic , Betacoronavirus/metabolism , Chiroptera/virology , Coronavirus Infections/metabolism , Dogs , Glycosylation , Host-Pathogen Interactions , Humans , Models, Animal , Pandemics , Pets , Pneumonia, Viral/metabolism , Protein Binding , Protein Conformation , Protein Interaction Domains and Motifs , Raccoons/virology , Sequence Alignment , Sequence Analysis, Protein , Swine , Viverridae/virology
14.
mBio ; 11(4)2020 07 21.
Article in English | MEDLINE | ID: covidwho-660818

ABSTRACT

To date, limited genetic changes in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome have been described. Here, we report a 382-nucleotide (nt) deletion in SARS-CoV-2 that truncates open reading frame 7b (ORF7b) and ORF8, removing the ORF8 transcription regulatory sequence (TRS) and eliminating ORF8 transcription. The earliest 382-nt deletion variant was detected in Singapore on 29 January 2020, with the deletion viruses circulating in the country and accounting for 23.6% (45/191) of SARS-CoV-2 samples screened in this study. SARS-CoV-2 with the same deletion has since been detected in Taiwan, and other ORF7b/8 deletions of various lengths, ranging from 62 nt to 345 nt, have been observed in other geographic locations, including Australia, Bangladesh, and Spain. Mutations or deletions in ORF8 of SARS-CoV have been associated with reduced replicative fitness and virus attenuation. In contrast, the SARS-CoV-2 382-nt deletion viruses showed significantly higher replicative fitness in vitro than the wild type, while no difference was observed in patient viral load, indicating that the deletion variant viruses retained their replicative fitness. A robust antibody response to ORF8 has been observed in SARS-CoV-2 infection, suggesting that the emergence of ORF8 deletions may be due to immune-driven selection and that further deletion variants may emerge during the sustained transmission of SARS-CoV-2 in humans.IMPORTANCE During the SARS epidemic in 2003/2004, a number of deletions were observed in ORF8 of SARS-CoV, and eventually deletion variants became predominant, leading to the hypothesis that ORF8 was an evolutionary hot spot for adaptation of SARS-CoV to humans. However, due to the successful control of the SARS epidemic, the importance of these deletions for the epidemiological fitness of SARS-CoV in humans could not be established. The emergence of multiple SARS-CoV-2 strains with ORF8 deletions, combined with evidence of a robust immune response to ORF8, suggests that the lack of ORF8 may assist with host immune evasion. In addition to providing a key insight into the evolutionary behavior of SARS-CoV-2 as the virus adapts to its new human hosts, the emergence of ORF8 deletion variants may also impact vaccination strategies.


Subject(s)
Betacoronavirus/genetics , Genome, Viral , Open Reading Frames , Base Sequence , Betacoronavirus/immunology , Betacoronavirus/physiology , Humans , Sequence Deletion , Virus Replication
16.
J Transl Med ; 18(1): 274, 2020 07 06.
Article in English | MEDLINE | ID: covidwho-657615

ABSTRACT

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have performed related clinical research. However, systematic reviews of the registered clinical trials are still lacking. Therefore, we conducted a systematic review of clinical trials for COVID-19 to summarize their characteristics. METHODS: This study is based on the PRISMA recommendations in the Cochrane handbook. The Chinese Clinical Registration Center and the ClinicalTrials.gov databases were searched to identify registered clinical trials related to COVID-19. The retrieval inception date was February 9, 2020. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias. RESULTS: A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) for COVID-19 were identified. The majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials have been completed; 34 trials were early clinical exploratory trials or in the pre-experiment stage, 13 trials were phase III, and four trials were phase IV. The intervention methods included traditional Chinese medicine in 26 trials, Western medicine in 30 trials, and integrated traditional Chinese medicine and Western medicine in 19 trials. The subjects were primarily non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60-200), and the median length of the trial periods was 179 d (IQR: 94-366 d). The main outcomes were clinical observation and examinations. Overall, the methodological quality of both the interventional trials and observational studies was low. CONCLUSIONS: Intensive clinical trials on the treatment of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be performed in China. However, based on the uncertain methodological quality, small sample size, and long trial duration, we will not be able to obtain reliable, high-quality clinical evidence regarding the treatment of COVID-19 in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for clinical trials of COVID-19 in the future.


Subject(s)
Betacoronavirus/physiology , Clinical Trials as Topic , Coronavirus Infections/virology , Pneumonia, Viral/virology , Humans , Observational Studies as Topic , Pandemics , Publication Bias , Risk , Treatment Outcome
17.
Antimicrob Resist Infect Control ; 9(1): 100, 2020 07 06.
Article in English | MEDLINE | ID: covidwho-657352

ABSTRACT

OBJECTIVES: To determine the risk of SARS-CoV-2 transmission by aerosols, to provide evidence on the rational use of masks, and to discuss additional measures important for the protection of healthcare workers from COVID-19. METHODS: Literature review and expert opinion. SHORT CONCLUSION: SARS-CoV-2, the pathogen causing COVID-19, is considered to be transmitted via droplets rather than aerosols, but droplets with strong directional airflow support may spread further than 2 m. High rates of COVID-19 infections in healthcare-workers (HCWs) have been reported from several countries. Respirators such as filtering face piece (FFP) 2 masks were designed to protect HCWs, while surgical masks were originally intended to protect patients (e.g., during surgery). Nevertheless, high quality standard surgical masks (type II/IIR according to European Norm EN 14683) appear to be as effective as FFP2 masks in preventing droplet-associated viral infections of HCWs as reported from influenza or SARS. So far, no head-to-head trials with these masks have been published for COVID-19. Neither mask type completely prevents transmission, which may be due to inappropriate handling and alternative transmission pathways. Therefore, compliance with a bundle of infection control measures including thorough hand hygiene is key. During high-risk procedures, both droplets and aerosols may be produced, reason why respirators are indicated for these interventions.


Subject(s)
Aerosols/analysis , Betacoronavirus/physiology , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Air Microbiology , Coronavirus Infections/virology , Health Personnel , Humans , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Pneumonia, Viral/virology , Protective Devices
19.
Infect Dis Poverty ; 9(1): 99, 2020 Jul 20.
Article in English | MEDLINE | ID: covidwho-655343

ABSTRACT

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has caused a public catastrophe and global concern. The main symptoms of COVID-19 are fever, cough, myalgia, fatigue and lower respiratory tract infection signs. Almost all populations are susceptible to the virus, and the basic reproduction number (R0) is 2.8-3.9. The fight against COVID-19 should have two aspects: one is the treatment of infected patients, and the other is the mobilization of the society to avoid the spread of the virus. The treatment of patients includes supportive treatment, antiviral treatment, and oxygen therapy. For patients with severe acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) and circulatory support are recommended. Plasma therapy and traditional Chinese medicine have also achieved good outcomes. This review is intended to summarize the research on this new coronavirus, to analyze the similarities and differences between COVID-19 and previous outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and to provide guidance regarding new methods of prevention, diagnosis and clinical treatment based on autodock simulations. METHODS: This review compares the multifaceted characteristics of the three coronaviruses including COVID-19, SARS and MERS. Our researchers take the COVID-19, SARS, and MERS as key words and search literatures in the Pubmed database. We compare them horizontally and vertically which respectively means concluding the individual characteristics of each coronavirus and comparing the similarities and differences between the three coronaviruses. RESULTS: We searched for studies on each outbreak and their solutions and found that the main biological differences among SARS-CoV-2, SARS-CoV and MERS-CoV are in ORF1a and the sequence of gene spike coding protein-S. We also found that the types and severity of clinical symptoms vary, which means that the diagnosis and nursing measures also require differentiation. In addition to the common route of transmission including airborne transmission, these three viruses have their own unique routes of transmission such as fecal-oral route of transmission COVID-19. CONCLUSIONS: In evolutionary history, these three coronaviruses have some similar biological features as well as some different mutational characteristics. Their receptors and routes of transmission are not all the same, which makes them different in clinical features and treatments. We discovered through the autodock simulations that Met124 plays a key role in the efficiency of drugs targeting ACE2, such as remdesivir, chloroquine, ciclesonide and niclosamide, and may be a potential target in COVID-19.


Subject(s)
Antiviral Agents/chemistry , Coronavirus Infections , Pandemics , Peptidyl-Dipeptidase A/chemistry , Pneumonia, Viral , Receptors, Virus/chemistry , Severe Acute Respiratory Syndrome , Animals , Antiviral Agents/metabolism , Betacoronavirus/genetics , Betacoronavirus/physiology , Betacoronavirus/ultrastructure , Clinical Laboratory Techniques , Clinical Trials as Topic , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Disease Reservoirs , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/physiology , Middle East Respiratory Syndrome Coronavirus/ultrastructure , Molecular Docking Simulation , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Pneumonia, Viral/transmission , Receptors, Virus/metabolism , SARS Virus/genetics , SARS Virus/physiology , SARS Virus/ultrastructure , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/transmission
20.
Nat Commun ; 11(1): 3618, 2020 07 17.
Article in English | MEDLINE | ID: covidwho-651635

ABSTRACT

Global emergencies caused by the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle-East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2 significantly endanger human health. The spike (S) glycoprotein is the key antigen and its conserved S2 subunit contributes to viral entry by mediating host-viral membrane fusion. However, structural information of the post-fusion S2 from these highly pathogenic human-infecting coronaviruses is still lacking. We used single-particle cryo-electron microscopy to show that the post-fusion SARS-CoV S2 forms a further rotated HR1-HR2 six-helix bundle and a tightly bound linker region upstream of the HR2 motif. The structures of pre- and post-fusion SARS-CoV S glycoprotein dramatically differ, resembling that of the Mouse hepatitis virus (MHV) and other class I viral fusion proteins. This structure suggests potential targets for the development of vaccines and therapies against a wide range of SARS-like coronaviruses.


Subject(s)
Betacoronavirus/chemistry , Betacoronavirus/physiology , Spike Glycoprotein, Coronavirus/chemistry , Amino Acid Motifs , Coronavirus/chemistry , Coronavirus/classification , Coronavirus Infections/virology , Cryoelectron Microscopy , Humans , Membrane Fusion , Models, Molecular , Pandemics , Pneumonia, Viral/virology , Protein Conformation , Protein Multimerization , Virus Internalization
SELECTION OF CITATIONS
SEARCH DETAIL