Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 92
Filter
1.
Front Cell Infect Microbiol ; 12: 845368, 2022.
Article in English | MEDLINE | ID: covidwho-1793038

ABSTRACT

Coronaviruses are the etiologic agents of several diseases. Coronaviruses of critical medical importance are characterized by highly inflammatory pathophysiology, involving severe pulmonary impairment and infection of multiple cell types within the body. Here, we discuss the interplay between coronaviruses and autophagy regarding virus life cycle, cell resistance, and inflammation, highlighting distinct mechanisms by which autophagy restrains inflammatory responses, especially those involved in coronavirus pathogenesis. We also address different autophagy modulators available and the rationale for drug repurposing as an attractive adjunctive therapy. We focused on pharmaceuticals being tested in clinical trials with distinct mechanisms but with autophagy as a common target. These autophagy modulators act in cell resistance to virus infection and immunomodulation, providing a double-strike to prevent or treat severe disease development and death from coronaviruses diseases.


Subject(s)
Coronavirus Infections , Coronavirus , Autophagy/physiology , Coronavirus/physiology , Coronavirus Infections/pathology , Humans , Inflammation , Viral Load , Virus Replication/physiology
2.
Int J Mol Sci ; 23(6)2022 Mar 18.
Article in English | MEDLINE | ID: covidwho-1760652

ABSTRACT

The presence of co-infections or superinfections with bacterial pathogens in COVID-19 patients is associated with poor outcomes, including increased morbidity and mortality. We hypothesized that SARS-CoV-2 and its components interact with the biofilms generated by commensal bacteria, which may contribute to co-infections. This study employed crystal violet staining and particle-tracking microrheology to characterize the formation of biofilms by Streptococcus pneumoniae and Staphylococcus aureus that commonly cause secondary bacterial pneumonia. Microrheology analyses suggested that these biofilms were inhomogeneous soft solids, consistent with their dynamic characteristics. Biofilm formation by both bacteria was significantly inhibited by co-incubation with recombinant SARS-CoV-2 spike S1 subunit and both S1 + S2 subunits, but not with S2 extracellular domain nor nucleocapsid protein. Addition of spike S1 and S2 antibodies to spike protein could partially restore bacterial biofilm production. Furthermore, biofilm formation in vitro was also compromised by live murine hepatitis virus, a related beta-coronavirus. Supporting data from LC-MS-based proteomics of spike-biofilm interactions revealed differential expression of proteins involved in quorum sensing and biofilm maturation, such as the AI-2E family transporter and LuxS, a key enzyme for AI-2 biosynthesis. Our findings suggest that these opportunistic pathogens may egress from biofilms to resume a more virulent planktonic lifestyle during coronavirus infections. The dispersion of pathogens from biofilms may culminate in potentially severe secondary infections with poor prognosis. Further detailed investigations are warranted to establish bacterial biofilms as risk factors for secondary pneumonia in COVID-19 patients.


Subject(s)
Antibiosis , Biofilms , Coronavirus/physiology , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism , Staphylococcus aureus/physiology , Streptococcus pneumoniae/physiology , Animals , Coinfection , Gene Expression Regulation, Bacterial , Humans , Mice , Microbial Interactions , Serogroup , Staphylococcus aureus/classification , Streptococcus pneumoniae/classification
3.
Nat Commun ; 13(1): 80, 2022 01 10.
Article in English | MEDLINE | ID: covidwho-1616982

ABSTRACT

Cross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Here we assess 52 COVID-19 household contacts to capture immune responses at the earliest timepoints after SARS-CoV-2 exposure. Using a dual cytokine FLISpot assay on peripheral blood mononuclear cells, we enumerate the frequency of T cells specific for spike, nucleocapsid, membrane, envelope and ORF1 SARS-CoV-2 epitopes that cross-react with human endemic coronaviruses. We observe higher frequencies of cross-reactive (p = 0.0139), and nucleocapsid-specific (p = 0.0355) IL-2-secreting memory T cells in contacts who remained PCR-negative despite exposure (n = 26), when compared with those who convert to PCR-positive (n = 26); no significant difference in the frequency of responses to spike is observed, hinting at a limited protective function of spike-cross-reactive T cells. Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Contact Tracing/methods , Cross Reactions/immunology , SARS-CoV-2/immunology , Adult , COVID-19/epidemiology , COVID-19/virology , Coronavirus/immunology , Coronavirus/physiology , Epitopes, T-Lymphocyte/immunology , Female , Humans , Male , /virology , Middle Aged , Pandemics/prevention & control , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Viral Proteins/genetics , Viral Proteins/immunology , Viral Proteins/metabolism , Young Adult
4.
Viruses ; 14(1)2021 12 30.
Article in English | MEDLINE | ID: covidwho-1580401

ABSTRACT

Medicinal chemistry optimization of a previously described stilbene inhibitor of HIV-1, 5350150 (2-(2-(5-nitro-2-thienyl)vinyl)quinoline), led to the identification of the thiazole-5-carboxamide derivative (GPS491), which retained potent anti-HIV-1 activity with reduced toxicity. In this report, we demonstrate that the block of HIV-1 replication by GPS491 is accompanied by a drastic inhibition of viral gene expression (IC50 ~ 0.25 µM), and alterations in the production of unspliced, singly spliced, and multiply spliced HIV-1 RNAs. GPS491 also inhibited the replication of adenovirus and multiple coronaviruses. Low µM doses of GPS491 reduced adenovirus infectious yield ~1000 fold, altered virus early gene expression/viral E1A RNA processing, blocked viral DNA amplification, and inhibited late (hexon) gene expression. Loss of replication of multiple coronaviruses (229E, OC43, SARS-CoV2) upon GPS491 addition was associated with the inhibition of viral structural protein expression and the formation of virus particles. Consistent with the observed changes in viral RNA processing, GPS491 treatment induced selective alterations in the accumulation/phosphorylation/function of splicing regulatory SR proteins. Our study establishes that a compound that impacts the activity of cellular factors involved in RNA processing can prevent the replication of several viruses with minimal effect on cell viability.


Subject(s)
Adenoviridae/drug effects , Antiviral Agents/pharmacology , Coronavirus/drug effects , HIV-1/drug effects , RNA Processing, Post-Transcriptional/drug effects , Thiazoles/pharmacology , Virus Replication/drug effects , Adenoviridae/physiology , Antiviral Agents/chemistry , Cell Line , Coronavirus/classification , Coronavirus/physiology , Gene Expression/drug effects , HIV-1/physiology , Humans , RNA Splicing Factors/metabolism , RNA, Viral/metabolism , Thiazoles/chemistry
5.
Int J Mol Sci ; 22(22)2021 Nov 09.
Article in English | MEDLINE | ID: covidwho-1512384

ABSTRACT

Coronaviruses cause diseases in humans and livestock. The SARS-CoV-2 is infecting millions of human beings, with high morbidity and mortality worldwide. The main protease (Mpro) of coronavirus plays a pivotal role in viral replication and transcription, which, in theory, is an attractive drug target for antiviral drug development. It has been extensively discussed whether Xanthohumol is able to help COVID-19 patients. Here, we report that Xanthohumol, a small molecule in clinical trials from hops (Humulus lupulus), was a potent pan-inhibitor for various coronaviruses by targeting Mpro, for example, betacoronavirus SARS-CoV-2 (IC50 value of 1.53 µM), and alphacoronavirus PEDV (IC50 value of 7.51 µM). Xanthohumol inhibited Mpro activities in the enzymatical assays, while pretreatment with Xanthohumol restricted the SARS-CoV-2 and PEDV replication in Vero-E6 cells. Therefore, Xanthohumol is a potent pan-inhibitor of coronaviruses and an excellent lead compound for further drug development.


Subject(s)
3C Viral Proteases/antagonists & inhibitors , Flavonoids/chemistry , Propiophenones/chemistry , Protease Inhibitors/chemistry , SARS-CoV-2/enzymology , 3C Viral Proteases/chemistry , 3C Viral Proteases/metabolism , Alphacoronavirus/enzymology , Alphacoronavirus/physiology , Amino Acid Sequence , Animals , Binding Sites , Biological Products/chemistry , Biological Products/metabolism , Biological Products/pharmacology , Biological Products/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Catalytic Domain , Chlorocebus aethiops , Coronavirus/enzymology , Coronavirus/physiology , Flavonoids/metabolism , Flavonoids/pharmacology , Flavonoids/therapeutic use , Humans , Molecular Docking Simulation , Propiophenones/metabolism , Propiophenones/pharmacology , Propiophenones/therapeutic use , Protease Inhibitors/metabolism , Protease Inhibitors/pharmacology , Protease Inhibitors/therapeutic use , SARS-CoV-2/isolation & purification , Sequence Alignment , Vero Cells , Virus Replication/drug effects
6.
Viruses ; 13(11)2021 10 29.
Article in English | MEDLINE | ID: covidwho-1488763

ABSTRACT

In the last two decades, several coronavirus (CoV) interspecies jumping events have occurred between bats and other animals/humans, leading to major epidemics/pandemics and high fatalities. The SARS epidemic in 2002/2003 had a ~10% fatality. The discovery of SARS-related CoVs in horseshoe bats and civets and genomic studies have confirmed bat-to-civet-to-human transmission. The MERS epidemic that emerged in 2012 had a ~35% mortality, with dromedaries as the reservoir. Although CoVs with the same genome organization (e.g., Tylonycteris BatCoV HKU4 and Pipistrellus BatCoV HKU5) were also detected in bats, there is still a phylogenetic gap between these bat CoVs and MERS-CoV. In 2016, 10 years after the discovery of Rhinolophus BatCoV HKU2 in Chinese horseshoe bats, fatal swine disease outbreaks caused by this virus were reported in southern China. In late 2019, an outbreak of pneumonia emerged in Wuhan, China, and rapidly spread globally, leading to >4,000,000 fatalities so far. Although the genome of SARS-CoV-2 is highly similar to that of SARS-CoV, patient zero and the original source of the pandemic are still unknown. To protect humans from future public health threats, measures should be taken to monitor and reduce the chance of interspecies jumping events, either occurring naturally or through recombineering experiments.


Subject(s)
COVID-19/virology , Chiroptera/virology , Coronavirus Infections/virology , Coronavirus/physiology , Host Adaptation , Severe Acute Respiratory Syndrome/virology , Alphacoronavirus/genetics , Alphacoronavirus/physiology , Animals , COVID-19/transmission , Coronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/veterinary , Host Specificity , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/physiology , SARS Virus/genetics , SARS Virus/physiology , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/transmission , Severe Acute Respiratory Syndrome/veterinary
7.
Viruses ; 13(11)2021 10 26.
Article in English | MEDLINE | ID: covidwho-1488755

ABSTRACT

Understanding the dynamic relationship between viral pathogens and cellular host factors is critical to furthering our knowledge of viral replication, disease mechanisms and development of anti-viral therapeutics. CRISPR genome editing technology has enhanced this understanding, by allowing identification of pro-viral and anti-viral cellular host factors for a wide range of viruses, most recently the cause of the COVID-19 pandemic, SARS-CoV-2. This review will discuss how CRISPR knockout and CRISPR activation genome-wide screening methods are a robust tool to investigate the viral life cycle and how other class 2 CRISPR systems are being repurposed for diagnostics.


Subject(s)
CRISPR-Cas Systems , Communicable Diseases, Emerging/virology , Coronavirus Infections/virology , Coronavirus/genetics , Gene Editing , Zika Virus Infection/virology , Zika Virus/genetics , COVID-19/diagnosis , COVID-19/virology , Clustered Regularly Interspaced Short Palindromic Repeats , Communicable Diseases, Emerging/diagnosis , Coronavirus/physiology , Coronavirus Infections/diagnosis , Host-Pathogen Interactions , Humans , SARS-CoV-2/genetics , Zika Virus/physiology , Zika Virus Infection/diagnosis
8.
Front Immunol ; 12: 652252, 2021.
Article in English | MEDLINE | ID: covidwho-1463468

ABSTRACT

The rapid outbreak of COVID-19 caused by the novel coronavirus SARS-CoV-2 in Wuhan, China, has become a worldwide pandemic affecting almost 204 million people and causing more than 4.3 million deaths as of August 11 2021. This pandemic has placed a substantial burden on the global healthcare system and the global economy. Availability of novel prophylactic and therapeutic approaches are crucially needed to prevent development of severe disease leading to major complications both acutely and chronically. The success in fighting this virus results from three main achievements: (a) Direct killing of the SARS-CoV-2 virus; (b) Development of a specific vaccine, and (c) Enhancement of the host's immune system. A fundamental necessity to win the battle against the virus involves a better understanding of the host's innate and adaptive immune response to the virus. Although the role of the adaptive immune response is directly involved in the generation of a vaccine, the role of innate immunity on RNA viruses in general, and coronaviruses in particular, is mostly unknown. In this review, we will consider the structure of RNA viruses, mainly coronaviruses, and their capacity to affect the lungs and the cardiovascular system. We will also consider the effects of the pattern recognition protein (PRP) trident composed by (a) Surfactant proteins A and D, mannose-binding lectin (MBL) and complement component 1q (C1q), (b) C-reactive protein, and (c) Innate and adaptive IgM antibodies, upon clearance of viral particles and apoptotic cells in lungs and atherosclerotic lesions. We emphasize on the role of pattern recognition protein immune therapies as a combination treatment to prevent development of severe respiratory syndrome and to reduce pulmonary and cardiovascular complications in patients with SARS-CoV-2 and summarize the need of a combined therapeutic approach that takes into account all aspects of immunity against SARS-CoV-2 virus and COVID-19 disease to allow mankind to beat this pandemic killer.


Subject(s)
COVID-19/immunology , Cardiovascular System/virology , Coronavirus Infections/immunology , Coronavirus/physiology , Immunotherapy/methods , Lung/virology , Receptors, Pattern Recognition/metabolism , SARS-CoV-2/physiology , Severe Acute Respiratory Syndrome/immunology , Animals , Cardiovascular System/pathology , Humans , Immunity, Innate , Lung/pathology
10.
J Med Virol ; 93(10): 5825-5832, 2021 10.
Article in English | MEDLINE | ID: covidwho-1432413

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has focused attention on the need to develop effective therapeutics against the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and also against other pathogenic coronaviruses. In this study, we report on a kind of bisbenzylisoquinoline alkaloid, neferine, as a pan-coronavirus entry inhibitor. Neferine effectively protected HEK293/hACE2 and HuH7 cell lines from infection by different coronaviruses pseudovirus particles (SARS-CoV-2, SARS-CoV-2 [D614G, N501Y/D614G, 501Y.V1, 501Y.V2, 501Y.V3 variants], SARS-CoV, MERS-CoV) in vitro, with median effect concentration (EC50 ) of 0.13-0.41 µM. Neferine blocked host calcium channels, thus inhibiting Ca2+ -dependent membrane fusion and suppressing virus entry. This study provides experimental data to support the fact that neferine may be a promising lead for pan-coronaviruses therapeutic drug development.


Subject(s)
Antiviral Agents/pharmacology , Benzylisoquinolines/pharmacology , Calcium/metabolism , SARS-CoV-2/drug effects , Virus Internalization/drug effects , COVID-19/virology , Cell Line , Coronavirus/drug effects , Coronavirus/physiology , HEK293 Cells , Humans , Isoquinolines/pharmacology , Phenols/pharmacology , SARS-CoV-2/physiology
11.
Arch Immunol Ther Exp (Warsz) ; 69(1): 25, 2021 Sep 16.
Article in English | MEDLINE | ID: covidwho-1411512

ABSTRACT

The term host defense peptides arose at the beginning to refer to those peptides that are part of the host's immunity. Because of their broad antimicrobial capacity and immunomodulatory activity, nowadays, they emerge as a hope to combat resistant multi-drug microorganisms and emerging viruses, such as the case of coronaviruses. Since the beginning of this century, coronaviruses have been part of different outbreaks and a pandemic, and they will be surely part of the next pandemics, this review analyses whether these peptides and their derivatives are ready to be part of the treatment of the next coronavirus pandemic.


Subject(s)
Antimicrobial Cationic Peptides/therapeutic use , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Pandemics , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/immunology , Anti-Inflammatory Agents/therapeutic use , Antimicrobial Cationic Peptides/chemical synthesis , Antimicrobial Cationic Peptides/immunology , Antiviral Agents/chemical synthesis , Antiviral Agents/immunology , Clinical Trials as Topic , Coronavirus/drug effects , Coronavirus/physiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Humans , Immunomodulation , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/immunology , Respiratory Tract Infections/virology
12.
Cell Mol Life Sci ; 78(21-22): 6735-6744, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1377320

ABSTRACT

Kallikrein-related peptidases (KLKs) or kallikreins have been linked to diverse (patho) physiological processes, such as the epidermal desquamation and inflammation, seminal clot liquefaction, neurodegeneration, and cancer. Recent mounting evidence suggests that KLKs also represent important regulators of viral infections. It is well-established that certain enveloped viruses, including influenza and coronaviruses, require proteolytic processing of their hemagglutinin or spike proteins, respectively, to infect host cells. Similarly, the capsid protein of the non-enveloped papillomavirus L1 should be proteolytically cleaved for viral uncoating. Consequently, extracellular or membrane-bound proteases of the host cells are instrumental for viral infections and represent potential targets for drug development. Here, we summarize how extracellular proteolysis mediated by the kallikreins is implicated in the process of influenza (and potentially coronavirus and papillomavirus) entry into host cells. Besides direct proteolytic activation of viruses, KLK5 and 12 promote viral entry indirectly through proteolytic cascade events, like the activation of thrombolytic enzymes that also can process hemagglutinin, while additional functions of KLKs in infection cannot be excluded. In the light of recent evidence, KLKs represent potential host targets for the development of new antivirals. Humanized animal models to validate their key functions in viral infections will be valuable.


Subject(s)
COVID-19/enzymology , COVID-19/virology , Host Microbial Interactions/physiology , Kallikreins/metabolism , SARS-CoV-2 , Virus Diseases/enzymology , Animals , Asthma/etiology , Coronavirus/genetics , Coronavirus/pathogenicity , Coronavirus/physiology , Host Microbial Interactions/genetics , Humans , Orthomyxoviridae/genetics , Orthomyxoviridae/pathogenicity , Orthomyxoviridae/physiology , Papillomavirus Infections/enzymology , Papillomavirus Infections/virology , Picornaviridae Infections/complications , Picornaviridae Infections/enzymology , Picornaviridae Infections/virology , Protein Processing, Post-Translational , Proteolysis , Rhinovirus/pathogenicity , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Varicella Zoster Virus Infection/enzymology , Varicella Zoster Virus Infection/virology , Viral Proteins/genetics , Viral Proteins/metabolism , Virus Diseases/virology , Virus Internalization
13.
Nat Commun ; 12(1): 5148, 2021 08 26.
Article in English | MEDLINE | ID: covidwho-1376197

ABSTRACT

Coronavirus infection in humans is usually associated to respiratory tract illnesses, ranging in severity from mild to life-threatening respiratory failure. The aryl hydrocarbon receptor (AHR) was recently identified as a host factor for Zika and dengue viruses; AHR antagonists boost antiviral immunity, decrease viral titers and ameliorate Zika-induced pathology in vivo. Here we report that AHR is activated by infection with different coronaviruses, potentially impacting antiviral immunity and lung epithelial cells. Indeed, the analysis of single-cell RNA-seq from lung tissue detected increased expression of AHR and AHR transcriptional targets, suggesting AHR signaling activation in SARS-CoV-2-infected epithelial cells from COVID-19 patients. Moreover, we detected an association between AHR expression and viral load in SARS-CoV-2 infected patients. Finally, we found that the pharmacological inhibition of AHR suppressed the replication in vitro of one of the causative agents of the common cold, HCoV-229E, and the causative agent of the COVID-19 pandemic, SARS-CoV-2. Taken together, these findings suggest that AHR activation is a common strategy used by coronaviruses to evade antiviral immunity and promote viral replication, which may also contribute to lung pathology. Future studies should further evaluate the potential of AHR as a target for host-directed antiviral therapy.


Subject(s)
Coronavirus Infections/metabolism , Coronavirus/physiology , Receptors, Aryl Hydrocarbon/metabolism , Signal Transduction , COVID-19/genetics , COVID-19/metabolism , COVID-19/virology , Coronavirus Infections/genetics , Coronavirus Infections/virology , Epithelial Cells/metabolism , Epithelial Cells/virology , Female , Humans , Male , Receptors, Aryl Hydrocarbon/genetics , SARS-CoV-2/physiology
14.
J Gen Virol ; 102(8)2021 08.
Article in English | MEDLINE | ID: covidwho-1368372

ABSTRACT

Infectious bronchitis virus (IBV) is an economically important coronavirus, causing damaging losses to the poultry industry worldwide as the causative agent of infectious bronchitis. The coronavirus spike (S) glycoprotein is a large type I membrane protein protruding from the surface of the virion, which facilitates attachment and entry into host cells. The IBV S protein is cleaved into two subunits, S1 and S2, the latter of which has been identified as a determinant of cellular tropism. Recent studies expressing coronavirus S proteins in mammalian and insect cells have identified a high level of glycosylation on the protein's surface. Here we used IBV propagated in embryonated hens' eggs to explore the glycan profile of viruses derived from infection in cells of the natural host, chickens. We identified multiple glycan types on the surface of the protein and found a strain-specific dependence on complex glycans for recognition of the S2 subunit by a monoclonal antibody in vitro, with no effect on viral replication following the chemical inhibition of complex glycosylation. Virus neutralization by monoclonal or polyclonal antibodies was not affected. Following analysis of predicted glycosylation sites for the S protein of four IBV strains, we confirmed glycosylation at 18 sites by mass spectrometry for the pathogenic laboratory strain M41-CK. Further characterization revealed heterogeneity among the glycans present at six of these sites, indicating a difference in the glycan profile of individual S proteins on the IBV virion. These results demonstrate a non-specific role for complex glycans in IBV replication, with an indication of an involvement in antibody recognition but not neutralisation.


Subject(s)
Coronavirus/physiology , Polysaccharides/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Alkaloids/chemistry , Alkaloids/pharmacology , Amino Acid Sequence , Animals , Binding Sites , Cells, Cultured , Chromatography, Liquid , Computational Biology/methods , Coronavirus/drug effects , Coronavirus Infections/veterinary , Gene Expression Regulation, Viral , Glycosylation/drug effects , Infectious bronchitis virus/physiology , Models, Molecular , Molecular Conformation , Molecular Weight , Neutralization Tests , Oligosaccharides/chemistry , Oligosaccharides/metabolism , Polysaccharides/chemistry , Poultry Diseases/virology , Protein Transport , Spectrometry, Mass, Electrospray Ionization , Spike Glycoprotein, Coronavirus/genetics , Structure-Activity Relationship , Virus Replication/drug effects
15.
Adv Genet ; 106: 75-100, 2020.
Article in English | MEDLINE | ID: covidwho-1363831

ABSTRACT

The origins and global spread of two recent, yet quite different, pandemic diseases is discussed and reviewed in depth: Candida auris, a eukaryotic fungal disease, and COVID-19 (SARS-CoV-2), a positive strand RNA viral respiratory disease. Both these diseases display highly distinctive patterns of sudden emergence and global spread, which are not easy to understand by conventional epidemiological analysis based on simple infection-driven human- to-human spread of an infectious disease (assumed to jump suddenly and thus genetically, from an animal reservoir). Both these enigmatic diseases make sense however under a Panspermia in-fall model and the evidence consistent with such a model is critically reviewed.


Subject(s)
Biological Evolution , Candidiasis/etiology , Communicable Diseases, Emerging/etiology , Coronavirus Infections/etiology , Origin of Life , Pneumonia, Viral/etiology , Animals , Betacoronavirus/isolation & purification , Betacoronavirus/physiology , COVID-19 , Candida/isolation & purification , Candida/physiology , Candidiasis/epidemiology , Communicable Diseases, Emerging/epidemiology , Coronavirus/isolation & purification , Coronavirus/physiology , Coronavirus Infections/epidemiology , Earth, Planet , Exobiology , Extraterrestrial Environment , Host-Pathogen Interactions/physiology , Humans , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2
16.
Viruses ; 13(8)2021 07 31.
Article in English | MEDLINE | ID: covidwho-1332907

ABSTRACT

Endemic human coronaviruses (HCoV) are capable of causing a range of diseases from the common cold to pneumonia. We evaluated the epidemiology and seasonality of endemic HCoVs in children hospitalized with clinical pneumonia and among community controls living in countries with a high HIV burden, namely South Africa and Zambia, between August 2011 to October 2013. Nasopharyngeal/oropharyngeal swabs were collected from all cases and controls and tested for endemic HCoV species and 12 other respiratory viruses using a multiplex real-time PCR assay. We found that the likelihood of detecting endemic HCoV species was higher among asymptomatic controls than cases (11% vs. 7.2%; 95% CI: 1.2-2.0). This was however only observed among children > 6 months and was mainly driven by the Betacoronavirus endemic species (HCoV-OC43 and -HKU1). Endemic HCoV species were detected through the year; however, in Zambia, the endemic Betacoronavirus species tended to peak during the winter months (May-August). There was no association between HIV status and endemic HCoV detection.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Coronavirus/physiology , Case-Control Studies , Child , Child, Preschool , Coronavirus/classification , Coronavirus/genetics , Coronavirus/isolation & purification , Coronavirus Infections/therapy , Hospitalization , Humans , Infant , Male , Nasopharynx/virology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Seasons , South Africa/epidemiology , Zambia/epidemiology
17.
Viruses ; 13(8)2021 07 30.
Article in English | MEDLINE | ID: covidwho-1335233

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus in humans, has expanded globally over the past year. COVID-19 remains an important subject of intensive research owing to its huge impact on economic and public health globally. Based on historical archives, the first coronavirus-related disease recorded was possibly animal-related, a case of feline infectious peritonitis described as early as 1912. Despite over a century of documented coronaviruses in animals, the global animal industry still suffers from outbreaks. Knowledge and experience handling animal coronaviruses provide a valuable tool to complement our understanding of the ongoing COVID-19 pandemic. In this review, we present an overview of coronaviruses, clinical signs, COVID-19 in animals, genome organization and recombination, immunopathogenesis, transmission, viral shedding, diagnosis, treatment, and prevention. By drawing parallels between COVID-19 in animals and humans, we provide perspectives on the pathophysiological mechanisms by which coronaviruses cause diseases in both animals and humans, providing a critical basis for the development of effective vaccines and therapeutics against these deadly viruses.


Subject(s)
Animal Diseases/virology , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Coronavirus/physiology , Animal Diseases/epidemiology , Animals , COVID-19/epidemiology , COVID-19/virology , Coronavirus/genetics , Coronavirus Infections/epidemiology , Humans , Public Health , SARS-CoV-2/genetics , SARS-CoV-2/physiology
18.
Biochimie ; 179: 229-236, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1326922

ABSTRACT

The ongoing pandemic of COVID-19 (Coronavirus Disease-2019), a respiratory disease caused by the novel coronavirus strain, SARS-CoV-2, has affected more than 42 million people already, with more than one million deaths worldwide (as of October 25, 2020). We are in urgent need of therapeutic interventions that target the host-virus interface, which requires a molecular understanding of the SARS-CoV-2 life-cycle. Like other positive-sense RNA viruses, coronaviruses remodel intracellular membranes to form specialized viral replication compartments, including double-membrane vesicles (DMVs), where viral RNA genome replication takes place. Here we review the current knowledge of the structure, lipid composition, function, and biogenesis of coronavirus-induced DMVs, highlighting the druggable viral and cellular factors that are involved in the formation and function of DMVs.


Subject(s)
Cell Membrane/metabolism , Coronavirus/physiology , Host Microbial Interactions , Virus Replication , Cell Membrane/virology , Humans , Molecular Targeted Therapy
19.
Cells ; 10(7)2021 07 19.
Article in English | MEDLINE | ID: covidwho-1323131

ABSTRACT

A novel coronavirus discovered in 2019 is a new strain of the Coronaviridae family (CoVs) that had not been previously identified in humans. It is known as SARS-CoV-2 for Severe Acute Respiratory Syndrome Coronavirus-2, whilst COVID-19 is the name of the disease associated with the virus. SARS-CoV-2 emerged over one year ago and still haunts the human community throughout the world, causing both healthcare and socioeconomic problems. SARS-CoV-2 is spreading with many uncertainties about treatment and prevention: the data available are limited and there are few randomized controlled trial data on the efficacy of antiviral or immunomodulatory agents. SARS-CoV-2 and its mutants are considered as unique within the Coronaviridae family insofar as they spread rapidly and can have severe effects on health. Although the scientific world has been succeeding in developing vaccines and medicines to combat COVID-19, the appearance and the spread of new, more aggressive mutants are posing extra problems for treatment. Nevertheless, our understanding of pandemics is increasing significantly due to this outbreak and is leading to the development of many different pharmacological, immunological and other treatments. This Review focuses on a subset of COVID-19 research, primarily the cytoskeleton-related physiological and pathological processes in which coronaviruses such as SARS-CoV-2 are intimately involved. The discovery of the exact mechanisms of the subversion of host cells by SARS-CoV-2 is critical to the validation of specific drug targets and effective treatments.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/pathology , Coronaviridae Infections/pathology , Cytoskeleton/pathology , Animals , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Coronaviridae Infections/drug therapy , Coronavirus/drug effects , Coronavirus/physiology , Cytoskeleton/drug effects , Host-Pathogen Interactions/drug effects , Humans , SARS-CoV-2/drug effects , SARS-CoV-2/physiology
20.
Expert Opin Ther Targets ; 25(6): 479-489, 2021 06.
Article in English | MEDLINE | ID: covidwho-1306504

ABSTRACT

Introduction: Enteroviruses are common viruses causing a huge number of acute and chronic infections and producing towering economic costs. Similarly, coronaviruses cause seasonal mild infections, epidemics, and even pandemics and can lead to severe respiratory symptoms. It is important to develop broadly acting antiviral molecules to efficiently tackle the infections caused by thes.Areas covered: This review illuminates the differences and similarities between enteroviruses and coronaviruses and examines the most appealing therapeutic targets to combat both virus groups. Publications of both virus groups and deposited structures discovered through PubMed to March 2021 for viral proteases have been evaluated.Expert opinion: The main protease of coronaviruses and enteroviruses share similarities in their structure and function. These proteases process their viral polyproteins and thus drugs that bind to the active site have potential to target both virus groups. It is important to develop drugs that target more evolutionarily conserved processes and proteins. Moreover, it is a wise strategy to concentrate on processes that are similar between several virus families.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus/physiology , Enterovirus/physiology , Animals , Coronavirus/drug effects , Coronavirus/enzymology , Cysteine Endopeptidases/metabolism , Enterovirus/drug effects , Enterovirus/enzymology , Humans , Substrate Specificity
SELECTION OF CITATIONS
SEARCH DETAIL