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1.
Int J Mol Sci ; 22(18)2021 Sep 17.
Article in English | MEDLINE | ID: covidwho-1430892

ABSTRACT

Previous studies reported on the broad-spectrum antiviral function of heparin. Here we investigated the antiviral function of magnesium-modified heparin and found that modified heparin displayed a significantly enhanced antiviral function against human adenovirus (HAdV) in immortalized and primary cells. Nuclear magnetic resonance analyses revealed a conformational change of heparin when complexed with magnesium. To broadly explore this discovery, we tested the antiviral function of modified heparin against herpes simplex virus type 1 (HSV-1) and found that the replication of HSV-1 was even further decreased compared to aciclovir. Moreover, we investigated the antiviral effect against the new severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and measured a 55-fold decreased viral load in the supernatant of infected cells associated with a 38-fold decrease in virus growth. The advantage of our modified heparin is an increased antiviral effect compared to regular heparin.


Subject(s)
Antiviral Agents/pharmacology , Heparin/pharmacology , Magnesium Chloride/pharmacology , Acyclovir/pharmacology , Adenoviruses, Human/drug effects , Adenoviruses, Human/physiology , Animals , Antiviral Agents/chemistry , CHO Cells , Cell Line, Tumor , Chlorocebus aethiops , Cricetulus , Drug Evaluation, Preclinical , Fibroblasts , Heparin/chemistry , Herpesvirus 1, Human/drug effects , Herpesvirus 1, Human/physiology , Humans , Magnesium Chloride/chemistry , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Molecular Structure , Primary Cell Culture , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Structure-Activity Relationship , Vero Cells , Viral Load/drug effects , Virus Replication/drug effects
2.
Biomed Res Int ; 2021: 9998420, 2021.
Article in English | MEDLINE | ID: covidwho-1398744

ABSTRACT

The global burden of viral infection, especially the current pandemics of SARS-CoV-2, HIV/AIDS, and hepatitis, is a very risky one. Additionally, HCV expresses the necessity for antiviral therapeutic elements. Venoms are known to contain an array of bioactive peptides that are commonly used in the treatment of various medical issues. Several peptides isolated from scorpion venom have recently been proven to possess an antiviral activity against several viral families. The aim of this review is to provide an up-to-date overview of scorpion antiviral peptides and to discuss their modes of action and potential biomedical application against different viruses.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Peptides/pharmacology , Scorpion Venoms/chemistry , Virus Diseases/drug therapy , Animals , Coronavirus/drug effects , HIV-1/drug effects , Hepatitis Viruses/drug effects , Herpesvirus 1, Human/drug effects , Humans , Measles virus/drug effects , Peptides/chemistry , Peptides/isolation & purification , Virus Diseases/virology
3.
Biochem Biophys Res Commun ; 575: 36-41, 2021 10 20.
Article in English | MEDLINE | ID: covidwho-1370449

ABSTRACT

Air spaces and material surfaces in a pathogen-contaminated environment can often be a source of infection to humans, and disinfection has become a common intervention focused on reducing the contamination levels. In this study, we examined the efficacy of SAIW, a unique electrolyzed water with chlorine-free, high pH, high concentration of dissolved hydrogen, and low oxygen reduction potential, for the inactivation of several viruses and bacteria. Infectivity assays revealed that initial viral titers of enveloped and non-enveloped viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, herpes simplex virus type 1, human coronavirus, feline calicivirus, and canine parvovirus, were reduced by 2.9- to 5.5-log10 within 30 s of SAIW exposure. Similarly, the culturability of three Gram-negative bacteria (Escherichia coli, Salmonella, and Legionella) dropped down by 1.9- to 4.9-log10 within 30 s of SAIW treatment. Mechanistically, treatment with SAIW was found to significantly decrease the binding and subsequent entry efficiencies of SARS-CoV-2 on Vero cells. Finally, we showed that this chlorine-free electrolytic ion water had no acute inhalation toxicity in mice, demonstrating that SAIW holds promise for a safer antiviral and antibacterial disinfectant.


Subject(s)
Anti-Infective Agents/pharmacology , Disinfectants/pharmacology , Disinfection/methods , SARS-CoV-2/drug effects , Virus Inactivation/drug effects , Water/pharmacology , Animals , Calicivirus, Feline/drug effects , Calicivirus, Feline/growth & development , Chlorocebus aethiops , Colony Count, Microbial , Electrolysis , Escherichia coli/drug effects , Escherichia coli/growth & development , Herpesvirus 1, Human/drug effects , Herpesvirus 1, Human/growth & development , Humans , Hydrogen-Ion Concentration , Influenza A virus/drug effects , Influenza A virus/growth & development , Legionella/drug effects , Legionella/growth & development , Mice , Parvovirus, Canine/drug effects , Parvovirus, Canine/growth & development , SARS-CoV-2/growth & development , Salmonella/drug effects , Salmonella/growth & development , Skin/drug effects , Vero Cells , Viral Load
4.
Virology ; 559: 165-172, 2021 07.
Article in English | MEDLINE | ID: covidwho-1198236

ABSTRACT

SARS coronavirus 1 (SARS-CoV-1) causes a respiratory infection that can lead to acute respiratory distress characterized by inflammation and high levels of cytokines in the lung tissue. In this study we constructed a herpes simplex virus 1 replication-defective mutant vector expressing SARS-CoV-1 spike protein as a potential vaccine vector and to probe the effects of spike protein on host cells. The spike protein expressed from this vector is functional in that it localizes to the surface of infected cells and induces fusion of ACE2-expressing cells. In immunized mice, the recombinant vector induced antibodies that bind to spike protein in an ELISA assay and that show neutralizing activity. The spike protein expressed from this vector can induce the expression of cytokines in an ACE2-independent, MyD88-dependent process. These results argue that the SARS-CoV-1 spike protein intrinsically activates signaling pathways that induce cytokines and contribute directly to the inflammatory process of SARS.


Subject(s)
Antibodies, Neutralizing/immunology , Herpesvirus 1, Human/genetics , Immunity, Innate , SARS Virus/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibodies, Viral/immunology , Cell Fusion , Cell Line , Cytokines/immunology , Genetic Vectors , Humans , Mice , SARS Virus/genetics , Signal Transduction , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Vaccines, Virus-Like Particle/immunology , Viral Vaccines/immunology
5.
Front Immunol ; 12: 676828, 2021.
Article in English | MEDLINE | ID: covidwho-1320577

ABSTRACT

In coronavirus disease 2019 (COVID-19), ulcerative lesions have been episodically reported in various segments of the gastrointestinal (GI) tract, including the oral cavity, oropharynx, esophagus, stomach and bowel. In this report, we describe an autopsy case of a COVID-19 patient who showed two undiagnosed ulcers at the level of the anterior and posterior walls of the hypopharynx. Molecular testing of viruses involved in pharyngeal ulcers demonstrated the presence of severe acute respiratory syndrome - coronavirus type 2 (SARS-CoV-2) RNA, together with herpes simplex virus 1 DNA. Histopathologic analysis demonstrated full-thickness lympho-monocytic infiltration (mainly composed of CD68-positive cells), with hemorrhagic foci and necrosis of both the mucosal layer and deep skeletal muscle fibers. Fibrin and platelet microthrombi were also found. Cytological signs of HSV-1 induced damage were not found. Cells expressing SARS-CoV-2 spike subunit 1 were immunohistochemically identified in the inflammatory infiltrations. Immunohistochemistry for HSV1 showed general negativity for inflammatory infiltration, although in the presence of some positive cells. Thus, histopathological, immunohistochemical and molecular findings supported a direct role by SARS-CoV-2 in producing local ulcerative damage, although a possible contributory role by HSV-1 reactivation cannot be excluded. From a clinical perspective, this autopsy report of two undiagnosed lesions put the question if ulcers along the GI tract could be more common (but frequently neglected) in COVID-19 patients.


Subject(s)
COVID-19/complications , Hypopharynx/pathology , SARS-CoV-2/isolation & purification , Ulcer/pathology , Aged , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Autopsy , Blood Platelets/metabolism , Blood Platelets/pathology , COVID-19/mortality , COVID-19/pathology , COVID-19/physiopathology , Gastrointestinal Tract/pathology , Herpesvirus 1, Human/genetics , Herpesvirus 1, Human/isolation & purification , Humans , Hypopharynx/virology , Immunohistochemistry , Inflammation/immunology , Inflammation/metabolism , Inflammation/virology , Lymphocytes/metabolism , Monocytes/metabolism , Mucous Membrane/pathology , Muscle, Skeletal/pathology , Necrosis/pathology , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/metabolism , Thrombosis/pathology , Ulcer/virology
6.
PLoS One ; 16(7): e0254129, 2021.
Article in English | MEDLINE | ID: covidwho-1291694

ABSTRACT

SARS-CoV-2 infection can lead to severe acute respiratory distress syndrome with the need of invasive ventilation. Pulmonary herpes simplex-1 (HSV-1) reactivation in invasively ventilated patients is a known phenomenon. To date very little is known about the frequency and the predisposing factors of HSV-1 reactivation in COVID-19. Therefore, we evaluated our cohort of invasively ventilated COVID-19 patients with severe pneumonia for HSV-1 in respiratory specimens and combined these results with functional immunomonitoring of the peripheral blood. Tracheal secretions and bronchial lavages were screened by PCR for HSV-1 positivity. Comprehensive immunophenotyping and quantitative gene expression analysis of Interferon-stimulated genes (IFI44L, MX1, RSAD2, ISIG15 and IFIT1) and IL-1 beta were performed in whole blood. Time course of infection beginning at symptom onset was grouped into three phases ("early" phase 1: day 1-10, "middle" phase 2: day 11-30 and "late" phase 3: day 31-40). Pulmonary HSV-1 reactivation was exclusively observed in the later phases 2 and 3 in 15 of 18 analyzed patients. By FACS analysis a significant increase in activated CD8 T cells (CD38+HLADR+) in phase 2 was found when compared with phase 1 (p<0.05). Expression of Interferon-stimulated genes (IFI44L, RSAD2 ISIG15, MX1, IFIT1) was significantly lower after HSV-1 detection than before. Taken together, reactivation of HSV-1 in the later phase of SARS-CoV-2- infection occurs in parallel with a drop of antiviral innate responsiveness as shown by decreased expression of Interferon-stimulated genes and a concurrent increase of highly activated CD38+HLADR+ CD8 T cells.


Subject(s)
COVID-19/therapy , Herpes Simplex/etiology , Herpesvirus 1, Human/physiology , Respiration, Artificial , Virus Activation , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/immunology , Female , Herpes Simplex/immunology , Herpesvirus 1, Human/immunology , Herpesvirus 1, Human/isolation & purification , Humans , Immunity, Innate , Male , Middle Aged , Respiration, Artificial/adverse effects , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
7.
Viruses ; 13(7)2021 06 29.
Article in English | MEDLINE | ID: covidwho-1289028

ABSTRACT

Vitis vinifera represents an important and renowned source of compounds with significant biological activity. Wines and winery bioproducts, such as grape pomace, skins, and seeds, are rich in bioactive compounds against a wide range of human pathogens, including bacteria, fungi, and viruses. However, little is known about the biological properties of vine leaves. The aim of this study was the evaluation of phenolic composition and antiviral activity of Vitis vinifera leaf extract against two human viruses: the Herpes simplex virus type 1 (HSV-1) and the pandemic and currently widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). About 40 phenolic compounds were identified in the extract by HPLC-MS/MS analysis: most of them were quercetin derivatives, others included derivatives of luteolin, kaempferol, apigenin, isorhamnetin, myricetin, chrysoeriol, biochanin, isookanin, and scutellarein. Leaf extract was able to inhibit both HSV-1 and SARS-CoV-2 replication in the early stages of infection by directly blocking the proteins enriched on the viral surface, at a very low concentration of 10 µg/mL. These results are very promising and highlight how natural extracts could be used in the design of antiviral drugs and the development of future vaccines.


Subject(s)
Antiviral Agents/pharmacology , Herpesvirus 1, Human/drug effects , Plant Extracts/pharmacology , Plant Leaves/chemistry , SARS-CoV-2/drug effects , Vitis/chemistry , A549 Cells , Animals , Biological Products/analysis , Biological Products/pharmacology , Cell Line , Chlorocebus aethiops , Chromatography, High Pressure Liquid , Humans , MCF-7 Cells , Phenols/pharmacology , Plant Extracts/analysis , Tandem Mass Spectrometry , Vero Cells
8.
Int J Mol Sci ; 22(12)2021 Jun 17.
Article in English | MEDLINE | ID: covidwho-1282513

ABSTRACT

Novel antiviral nanotherapeutics, which may inactivate the virus and block it from entering host cells, represent an important challenge to face viral global health emergencies around the world. Using a combination of bioorthogonal copper-catalyzed 1,3-dipolar alkyne/azide cycloaddition (CuAAC) and photoinitiated thiol-ene coupling, monofunctional and bifunctional peptidodendrimer conjugates were obtained. The conjugates are biocompatible and demonstrate no toxicity to cells at biologically relevant concentrations. Furthermore, the orthogonal addition of multiple copies of two different antiviral peptides on the surface of a single dendrimer allowed the resulting bioconjugates to inhibit Herpes simplex virus type 1 at both the early and the late stages of the infection process. The presented work builds on further improving this attractive design to obtain a new class of therapeutics.


Subject(s)
Antiviral Agents/pharmacology , Dendrimers/pharmacology , Glycoproteins , Herpesvirus 1, Human , Peptides/pharmacology , Viral Proteins , Amino Acid Sequence , Animals , Antiviral Agents/chemistry , CHO Cells , Cell Line , Cell Survival/drug effects , Chemical Phenomena , Chemistry Techniques, Synthetic , Chromatography, High Pressure Liquid , Cricetulus , Dendrimers/chemistry , Glycoproteins/chemistry , Herpesvirus 1, Human/metabolism , Microbial Sensitivity Tests , Molecular Structure , Peptides/chemistry , Spectrum Analysis , Viral Proteins/chemistry
9.
Cells ; 10(5)2021 05 04.
Article in English | MEDLINE | ID: covidwho-1223958

ABSTRACT

Sphingolipids are important structural membrane components and, together with cholesterol, are often organized in lipid rafts, where they act as signaling molecules in many cellular functions. They play crucial roles in regulating pathobiological processes, such as cancer, inflammation, and infectious diseases. The bioactive metabolites ceramide, sphingosine-1-phosphate, and sphingosine have been shown to be involved in the pathogenesis of several microbes. In contrast to ceramide, which often promotes bacterial and viral infections (for instance, by mediating adhesion and internalization), sphingosine, which is released from ceramide by the activity of ceramidases, kills many bacterial, viral, and fungal pathogens. In particular, sphingosine is an important natural component of the defense against bacterial pathogens in the respiratory tract. Pathologically reduced sphingosine levels in cystic fibrosis airway epithelial cells are normalized by inhalation of sphingosine, and coating plastic implants with sphingosine prevents bacterial infections. Pretreatment of cells with exogenous sphingosine also prevents the viral spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from interacting with host cell receptors and inhibits the propagation of herpes simplex virus type 1 (HSV-1) in macrophages. Recent examinations reveal that the bactericidal effect of sphingosine might be due to bacterial membrane permeabilization and the subsequent death of the bacteria.


Subject(s)
Bacterial Infections/immunology , Mycoses/immunology , Signal Transduction/immunology , Sphingosine/metabolism , Virus Diseases/immunology , Animals , Bacterial Infections/drug therapy , Bacterial Infections/metabolism , Bacterial Infections/microbiology , Cell Wall/drug effects , Ceramides/metabolism , Disease Models, Animal , Herpesvirus 1, Human/immunology , Humans , Lysophospholipids/metabolism , Membrane Microdomains/immunology , Membrane Microdomains/metabolism , Mycoses/drug therapy , Mycoses/metabolism , Mycoses/microbiology , SARS-CoV-2/immunology , Sphingolipids/metabolism , Sphingosine/analogs & derivatives , Sphingosine/pharmacology , Sphingosine/therapeutic use , Virus Diseases/drug therapy , Virus Diseases/metabolism , Virus Diseases/virology
10.
Medicina (Kaunas) ; 57(5)2021 Apr 24.
Article in English | MEDLINE | ID: covidwho-1201634

ABSTRACT

Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious blindness worldwide. Most of the initial infection cases manifest as acute epithelial keratitis. Reactivation of herpesviruses is common in critically ill patients, including patients with severe Coronavirus disease (COVID-19). However, the data on COVID-19-related ocular infections is sparse, despite recent observations that more than 30% of COVID-19-infected patients had ocular manifestations. We report five cases of HSV-1 keratitis in COVID-19 patients. In total, five COVID-19 patients underwent ophthalmic examination, showing similar symptoms, including photophobia, tearing, decreased vision, eye redness, and pain. After initial assessment, tests of visual acuity and corneal sensitivity, a fluorescein staining test, and complete anterior and posterior segment examinations were performed. A diagnosis of HSV-1 keratitis was confirmed in all cases. Therapy was initiated using a local and systemic antiviral approach together with local antibiotic and mydriatic therapy. The complete reduction of keratitis symptoms and a clear cornea was achieved in all patients within 2 weeks. SARS-CoV-2 infection may be a risk factor for developing HSV-1 keratitis, or it may act as a potential activator of this ocular disease.


Subject(s)
COVID-19 , Herpesvirus 1, Human , Keratitis, Herpetic , Antiviral Agents/therapeutic use , Humans , Keratitis, Herpetic/diagnosis , Keratitis, Herpetic/drug therapy , SARS-CoV-2
11.
BMJ Case Rep ; 14(3)2021 Mar 10.
Article in English | MEDLINE | ID: covidwho-1133189

ABSTRACT

Neonatal herpes simplex virus (HSV) infection is rare, with an estimated incidence of 3.58 per 100 000 live births in the UK and should be suspected in any newborn with fever and bacterial culture-negative sepsis. We describe a case of a previously well full-term male neonate who presented with persistent fever and elevated ferritin level that was carried out during the era of the COVID-19 pandemic as part of SARS-CoV-2 panel investigations. Despite the initial negative HSV serology, HSV-1 PCR from a scalp lesion returned positive. He made a full recovery after acyclovir therapy. This case highlights the importance of maintaining a high clinical index of suspicion of HSV infection in any febrile neonate even with absence of maternal history and negative serology, particularly if associated with hyperferritinaemia. We also address the challenge of interpreting inflammatory biomarkers' results for SARS-CoV-2 infection in neonates.


Subject(s)
COVID-19/epidemiology , Ferritins/blood , Fever/etiology , Herpes Simplex/diagnosis , Pregnancy Complications, Infectious/diagnosis , Acyclovir/therapeutic use , Antiviral Agents/therapeutic use , Female , Herpes Simplex/complications , Herpes Simplex/drug therapy , Herpesvirus 1, Human/isolation & purification , Humans , Infant, Newborn , Male , Pandemics , Polymerase Chain Reaction , Pregnancy , Pregnancy Complications, Infectious/drug therapy , SARS-CoV-2 , Treatment Outcome
12.
PLoS One ; 16(2): e0247396, 2021.
Article in English | MEDLINE | ID: covidwho-1090539

ABSTRACT

Among various delivery systems for vaccine and drug delivery, cell-penetrating peptides (CPPs) have been known as a potent delivery system because of their capability to penetrate cell membranes and deliver some types of cargoes into cells. Several CPPs were found in the proteome of viruses such as Tat originated from human immunodeficiency virus-1 (HIV-1), and VP22 derived from herpes simplex virus-1 (HSV-1). In the current study, a wide-range of CPPs was identified in the proteome of SARS-CoV-2, a new member of coronaviruses family, using in silico analyses. These CPPs may play a main role for high penetration of virus into cells and infection of host. At first, we submitted the proteome of SARS-CoV-2 to CellPPD web server that resulted in a huge number of CPPs with ten residues in length. Afterward, we submitted the predicted CPPs to C2Pred web server for evaluation of the probability of each peptide. Then, the uptake efficiency of each peptide was investigated using CPPred-RF and MLCPP web servers. Next, the physicochemical properties of the predicted CPPs including net charge, theoretical isoelectric point (pI), amphipathicity, molecular weight, and water solubility were calculated using protparam and pepcalc tools. In addition, the probability of membrane binding potential and cellular localization of each CPP were estimated by Boman index using APD3 web server, D factor, and TMHMM web server. On the other hand, the immunogenicity, toxicity, allergenicity, hemolytic potency, and half-life of CPPs were predicted using various web servers. Finally, the tertiary structure and the helical wheel projection of some CPPs were predicted by PEP-FOLD3 and Heliquest web servers, respectively. These CPPs were divided into: a) CPP containing tumor homing motif (RGD) and/or tumor penetrating motif (RXXR); b) CPP with the highest Boman index; c) CPP with high half-life (~100 hour) in mammalian cells, and d) CPP with +5.00 net charge. Based on the results, we found a large number of novel CPPs with various features. Some of these CPPs possess tumor-specific motifs which can be evaluated in cancer therapy. Furthermore, the novel and potent CPPs derived from SARS-CoV-2 may be used alone or conjugated to some sequences such as nuclear localization sequence (NLS) for vaccine and drug delivery.


Subject(s)
COVID-19 Vaccines/chemistry , Cell-Penetrating Peptides/chemistry , Computational Biology , Computer Simulation , Drug Delivery Systems , Proteome , SARS-CoV-2/chemistry , Animals , COVID-19 , COVID-19 Vaccines/genetics , COVID-19 Vaccines/metabolism , Cell-Penetrating Peptides/genetics , Cell-Penetrating Peptides/metabolism , HIV-1/chemistry , HIV-1/genetics , Herpesvirus 1, Human/chemistry , Herpesvirus 1, Human/genetics , Humans , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Viral Structural Proteins/chemistry , Viral Structural Proteins/genetics , tat Gene Products, Human Immunodeficiency Virus/chemistry , tat Gene Products, Human Immunodeficiency Virus/genetics
13.
Viruses ; 13(2)2021 02 20.
Article in English | MEDLINE | ID: covidwho-1090285

ABSTRACT

In the face of new emerging respiratory viruses, such as SARS-CoV2, vaccines and drug therapies are not immediately available to curb the spread of infection. Non-pharmaceutical interventions, such as mask-wearing and social distance, can slow the transmission. However, both mask and social distance have not prevented the spread of respiratory viruses SARS-CoV2 within the US. There is an urgent need to develop an intervention that could reduce the spread of respiratory viruses. The key to preventing transmission is to eliminate the emission of SARS-CoV2 from an infected person and stop the virus from propagating in the human population. Rhamnolipids are environmentally friendly surfactants that are less toxic than the synthetic surfactants. In this study, rhamnolipid products, 222B, were investigated as disinfectants against enveloped viruses, such as bovine coronavirus and herpes simplex virus 1 (HSV-1). The 222B at 0.009% and 0.0045% completely inactivated 6 and 4 log PFU/mL of HSV-1 in 5-10 min, respectively. 222B at or below 0.005% is also biologically safe. Moreover, 50 µL of 222B at 0.005% on ~1 cm2 mask fabrics or plastic surface can inactivate ~103 PFU HSV-1 in 3-5 min. These results suggest that 222B coated on masks or plastic surface can reduce the emission of SARS-CoV2 from an infected person and stop the spread of SARS-CoV2.


Subject(s)
COVID-19 , Coronavirus, Bovine/drug effects , Disinfectants/pharmacology , Glycolipids/pharmacology , Herpesvirus 1, Human/drug effects , Surface-Active Agents/pharmacology , COVID-19/prevention & control , COVID-19/transmission , Humans
14.
Med Hypotheses ; 146: 110447, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1023713

ABSTRACT

The pathogen burden, defined by the frequency of antibodies to several viruses and a parasite, is greater in Hispanic whites and black populations than it is in non-Hispanic whites, in the USA. The poor and those without higher education also have higher pathogen burdens. The most frequent pathogen that was measured, was the Herpes simplex virus type 1 (HSV-1). This virus can inactivate most of the elements in the immune system, that are designed to protect against the incursions of viruses, bacteria and other pathogens. HSV-1 can also damage the blood brain barrier (BBB), which prevents the entry of pathogens into the central nervous system. Without the help of HSV-1, the COVID-19 virus may not be able to cause serious illness or death in humans. A prophylactic treatment to contain HSV-1, could be vital in the fight against COVID-19.


Subject(s)
COVID-19/epidemiology , Herpes Simplex/epidemiology , Herpesvirus 1, Human/pathogenicity , Models, Biological , African Americans , Blood-Brain Barrier , COVID-19/prevention & control , COVID-19/virology , Herpes Simplex/prevention & control , Herpes Simplex/virology , Host Microbial Interactions , Humans , Pandemics , SARS-CoV-2/pathogenicity , United States/epidemiology
16.
Cell Rep ; 33(5): 108345, 2020 11 03.
Article in English | MEDLINE | ID: covidwho-898566

ABSTRACT

Bat cells and tissue have elevated basal expression levels of antiviral genes commonly associated with interferon alpha (IFNα) signaling. Here, we show Interferon Regulatory Factor 1 (IRF1), 3, and 7 levels are elevated in most bat tissues and that, basally, IRFs contribute to the expression of type I IFN ligands and high expression of interferon regulated genes (IRGs). CRISPR knockout (KO) of IRF 1/3/7 in cells reveals distinct subsets of genes affected by each IRF in an IFN-ligand signaling-dependent and largely independent manner. As the master regulators of innate immunity, the IRFs control the kinetics and maintenance of the IRG response and play essential roles in response to influenza A virus (IAV), herpes simplex virus 1 (HSV-1), Melaka virus/Pteropine orthoreovirus 3 Melaka (PRV3M), and Middle East respiratory syndrome-related coronavirus (MERS-CoV) infection. With its differential expression in bats compared to that in humans, this highlights a critical role for basal IRF expression in viral responses and potentially immune cell development in bats with relevance for IRF function in human biology.


Subject(s)
Chiroptera/immunology , Gene Expression Regulation/immunology , Interferon Regulatory Factor-1/immunology , Interferon Regulatory Factor-7/immunology , Virus Diseases/immunology , Animals , Herpesvirus 1, Human/immunology , Influenza A virus/immunology , Middle East Respiratory Syndrome Coronavirus/immunology , Orthoreovirus/immunology
17.
Cell Rep ; 33(5): 108339, 2020 11 03.
Article in English | MEDLINE | ID: covidwho-898565

ABSTRACT

Here, we report our studies of immune-mediated regulation of Zika virus (ZIKV), herpes simplex virus 1 (HSV-1), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the human cornea. We find that ZIKV can be transmitted via corneal transplantation in mice. However, in human corneal explants, we report that ZIKV does not replicate efficiently and that SARS-CoV-2 does not replicate at all. Additionally, we demonstrate that type III interferon (IFN-λ) and its receptor (IFNλR1) are expressed in the corneal epithelium. Treatment of human corneal explants with IFN-λ, and treatment of mice with IFN-λ eye drops, upregulates antiviral interferon-stimulated genes. In human corneal explants, blockade of IFNλR1 enhances replication of ZIKV and HSV-1 but not SARS-CoV-2. In addition to an antiviral role for IFNλR1 in the cornea, our results suggest that the human cornea does not support SARS-CoV-2 infection despite expression of ACE2, a SARS-CoV-2 receptor, in the human corneal epithelium.


Subject(s)
Betacoronavirus/physiology , Cornea/virology , Coronavirus Infections/transmission , Herpesvirus 1, Human/physiology , Interferons/immunology , Pneumonia, Viral/transmission , Zika Virus/physiology , Animals , Betacoronavirus/immunology , COVID-19 , Cornea/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Herpes Simplex/immunology , Herpes Simplex/transmission , Herpes Simplex/virology , Humans , Mice , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Virus Replication/physiology , Zika Virus Infection/immunology , Zika Virus Infection/transmission , Zika Virus Infection/virology
18.
Anal Chem ; 92(16): 11297-11304, 2020 08 18.
Article in English | MEDLINE | ID: covidwho-733551

ABSTRACT

Viruses are infections species that infect a large spectrum of living systems. Although displaying a wide variety of shapes and sizes, they are all composed of nucleic acid encapsulated into a protein capsid. After virions enter the host cell, they replicate to produce multiple copies of themselves. They then lyse the host, releasing virions to infect new cells. The high proliferation rate of viruses is the underlying cause of their fast transmission among living species. Although many viruses are harmless, some of them are responsible for severe diseases such as AIDS, viral hepatitis, and flu. Traditionally, electron microscopy is used to identify and characterize viruses. This approach is time- and labor-consuming, which is problematic upon pandemic proliferation of previously unknown viruses, such as H1N1 and COVID-19. Herein, we demonstrate a novel diagnosis approach for label-free identification and structural characterization of individual viruses that is based on a combination of nanoscale Raman and infrared spectroscopy. Using atomic force microscopy-infrared (AFM-IR) spectroscopy, we were able to probe structural organization of the virions of Herpes Simplex Type 1 viruses and bacteriophage MS2. We also showed that tip-enhanced Raman spectroscopy (TERS) could be used to reveal protein secondary structure and amino acid composition of the virus surface. Our results show that AFM-IR and TERS provide different but complementary information about the structure of complex biological specimens. This structural information can be used for fast and reliable identification of viruses. This nanoscale bimodal imaging approach can be also used to investigate the origin of viral polymorphism and study mechanisms of virion assembly.


Subject(s)
Microscopy, Atomic Force/methods , Nanostructures/chemistry , Spectrum Analysis, Raman/methods , Virion/chemistry , Animals , Betacoronavirus/isolation & purification , Betacoronavirus/physiology , COVID-19 , Capsid/chemistry , Chlorocebus aethiops , Coronavirus Infections/pathology , Coronavirus Infections/virology , Cryoelectron Microscopy , Discriminant Analysis , Herpesvirus 1, Human/physiology , Humans , Influenza A Virus, H1N1 Subtype/physiology , Least-Squares Analysis , Levivirus/metabolism , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Protein Structure, Tertiary , SARS-CoV-2 , Vero Cells
19.
Clin Infect Dis ; 73(1): e252-e255, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-729104

ABSTRACT

We report two fatal cases of acute liver failure secondary to herpes simplex virus 1 infection in COVID-19 patients, following tocilizumab and corticosteroid therapy. Screening for and prompt recognition of herpes simplex virus 1 reactivation in these patients, undergoing immunomodulatory treatment, may have potentially relevant clinical consequences.


Subject(s)
COVID-19 , Herpes Simplex , Herpesvirus 1, Human , Liver Failure, Acute , Humans , Immunomodulation , SARS-CoV-2
20.
Neurol Sci ; 41(6): 1361-1364, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-267579

ABSTRACT

CASE REPORT: We describe the case of a 73-year-old woman who was diagnosed with herpes simplex virus-1 encephalitis during the COVID-19 pandemic. The diagnosis was somehow delayed because relatives were initially cautious in bringing the patient to the hospital and, here, the work-up focus was on coronavirusrelated aspects as the patient was initially reputed to be infected with COVID-19. CONCLUSIONS: During the current viral outbreak, physicians should not neglect the possibility of other diseases that represent neurological emergencies and require immediate recognition and treatment.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnostic imaging , Delayed Diagnosis , Encephalitis, Herpes Simplex/diagnostic imaging , Herpesvirus 1, Human , Pneumonia, Viral/diagnostic imaging , Aged , COVID-19 , Coronavirus Infections/therapy , Diagnosis, Differential , Encephalitis, Herpes Simplex/therapy , Female , Humans , Pandemics , Pneumonia, Viral/therapy , SARS-CoV-2
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