A5057342833- Virology and Viral Diseases
- Respiratory viral infections research
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Vectors
- Influenza Virus Research Studies
- COVID-19 Clinical Research Studies
- vaccines and immunoinformatics approaches
- Mosquito-borne diseases and control
- HIV Research and Treatment
- Bacteriophages and microbial interactions
- interferon and immune responses
- Parvovirus B19 Infection Studies
- Virus-based gene therapy research
- Lipid Membrane Structure and Behavior
- Neonatal Respiratory Health Research
- Viral Infections and Immunology Research
- Animal Virus Infections Studies
- Monoclonal and Polyclonal Antibodies Research
- Viral Infections and Outbreaks Research
- Congenital Diaphragmatic Hernia Studies
- Viral gastroenteritis research and epidemiology
- Pneumonia and Respiratory Infections
- Trypanosoma species research and implications
- Erythrocyte Function and Pathophysiology
- Hemoglobinopathies and Related Disorders
Columbia University Irving Medical Center
2016-2025
University of Campania "Luigi Vanvitelli"
2018-2025
Columbia University
2020-2025
Cornell University
2007-2016
Virginia Commonwealth University
2006
Icahn School of Medicine at Mount Sinai
2001-2005
Istituti di Ricovero e Cura a Carattere Scientifico
2001
Istituto Giannina Gaslini
1996-2001
Despite limited genomic diversity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown a wide range of clinical manifestations in different patient populations. The mechanisms behind these host differences are still unclear. Here, we examined response gene expression across infection status, viral load, age, and sex among shotgun RNA sequencing profiles nasopharyngeal (NP) swabs from 430 individuals with PCR-confirmed SARS-CoV-2 54 negative controls. induced strong...
Halting transmission The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein binds to host cells and initiates membrane fusion cell infection. This stage in the virus life history is currently a target for drug inhibition. De Vries et al. designed highly stable lipoprotein inhibitors complementary conserved repeat C terminus of S that integrate into membranes inhibit conformational changes necessary fusion. authors tested performance lipoproteins as...
Abstract We have assessed antiviral activity and induction of protective immunity fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The block infection cell lines lung-derived organotypic cultures. Intranasal administration allows maintenance homeostatic transcriptomic immune profile lungs, prevents body-weight loss, decreases viral load shedding, protects death caused by...
We describe an antiviral small molecule, LJ001, effective against numerous enveloped viruses including Influenza A, filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses, flaviviruses, and HIV-1. In sharp contrast, the compound had no effect on infection of nonenveloped viruses. vitro in vivo assays showed overt toxicity. LJ001 specifically intercalated into viral membranes, irreversibly inactivated virions while leaving functionally intact envelope proteins, inhibited entry...
In the paramyxovirus cell entry process, receptor binding triggers conformational changes in fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions F have been shown inhibit by preventing formation of fusogenic six-helix bundle. We recently showed that addition a cholesterol group HRC peptides active against Nipah virus targets these where occurs, dramatically increasing their antiviral effect. this work, we report...
Respiratory viruses are among the first pathogens encountered by young children, and significant impact of these viral infections on developing lung is poorly understood. Circulating suited to environment human different from those grown in cultured cells. We modeled respiratory virus that occur children or infect distal using organoids represent entire infant lung. These 3D organoids, derived pluripotent stem cells, develop into branching airway alveolar structures provide a tissue...
The emergence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent 2019 disease (COVID-19), has erupted into a global pandemic that led to tens millions infections and hundreds thousands deaths worldwide. development therapeutics treat infection or as prophylactics halt viral transmission spread is urgently needed. SARS-CoV-2 relies on structural rearrangements within spike (S) glycoprotein mediate fusion host cell membranes. Here, we describe...
SARS-CoV-2 cell entry is completed after viral spike (S) protein–mediated membrane fusion between and host membranes. Stable prefusion postfusion S structures have been resolved by cryo–electron microscopy tomography, but the refolding intermediates on pathway are transient not examined. We used an antiviral lipopeptide inhibitor to arrest protein thereby capture as proteins interact with hACE2 fusion-activating proteases cell-derived target Cryo–electron tomography imaged both extended...
We describe an antiviral small molecule, LJ001, effective against numerous enveloped viruses including Influenza A, filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses, flaviviruses, and HIV-1. In sharp contrast, the compound had no effect on infection of nonenveloped viruses. vitro in vivo assays showed overt toxicity. LJ001 specifically intercalated into viral membranes, irreversibly inactivated virions while leaving functionally intact envelope proteins, inhibited entry...
The fusion of enveloped viruses with the host cell is driven by specialized proteins to initiate infection. "class I" harbor two regions, typically heptad repeat (HR) domains, which are central complex conformational changes leading fusion: first (HRN) adjacent peptide, while second (HRC) immediately precedes transmembrane domain. Peptides derived from HR regions can inhibit fusion, and one T20 (enfuvirtide), in clinical use for HIV-1. For paramyxoviruses, activities membrane proteins,...
ABSTRACT Clinical manifestations of COVID-19 caused by the novel coronavirus SARS-CoV-2 are associated with age. While children largely spared from severe respiratory disease, they can present a SARS-CoV-2-associated multisystem inflammatory syndrome (MIS-C) similar to Kawasaki’s disease. Here, we show distinct antibody (Ab) responses in MIS-C compared adults causing acute distress (ARDS), and those who recovered mild There was reduced breadth specificity anti-SARS-CoV-2-specific antibodies...
SARS-CoV-2 has caused a global pandemic of COVID-19 since its emergence in December 2019. The infection causes severe acute respiratory syndrome and may also spread to central nervous system leading neurological sequelae. We have developed characterized two new organotypic cultures from hamster brainstem lung tissues that offer unique opportunity study the early steps viral screening antivirals. These models are not dedicated investigate how virus reaches brain. However, they allow...
Paramyxoviruses—including important pathogens like parainfluenza, measles, and Nipah viruses—use a receptor binding protein [hemagglutinin-neuraminidase (HN) for parainfluenza] fusion (F), acting in complex, to enter cells. We use cryo–electron tomography visualize the complex of human parainfluenza virus 3 (HN/F) on surface authentic clinical viruses at subnanometer resolution sufficient answer mechanistic questions. An HN loop inserts pocket F, showing how remains ready but quiescent state...
SARS-CoV-2 infection for most children results in mild or minimal symptoms, though rare cases severe disease can develop, including a multisystem inflammatory syndrome (MIS-C) with myocarditis. Here, we present longitudinal profiling of immune responses during acute and following recovery who developed MIS-C, relative to experienced more typical symptoms COVID-19. T cells MIS-C exhibited transient signatures activation, inflammation, tissue residency which correlated cardiac severity, while...
Measles virus (MeV) presents a public health threat that is escalating as vaccine coverage in the general population declines and populations of immunocompromised individuals, who cannot be vaccinated, increase. There are no approved therapeutics for MeV. Neutralizing antibodies targeting viral fusion one potential therapeutic approach but have not yet been structurally characterized or advanced to clinical use. We present cryo-electron microscopy (cryo-EM) structures prefusion F alone...
ABSTRACT The hemagglutinin-neuraminidase (HN) protein of paramyxoviruses carries out three discrete activities that each affect the ability HN to promote viral fusion and entry: receptor binding, cleaving (neuraminidase), triggering protein. interrelationship between binding fusion-triggering functions has not been clear. For human parainfluenza type 3 (HPIV3), one bifunctional site on can carry both neuraminidase activities, this site's be inhibited by small analog zanamivir. We now report...
Nipah (NiV) and Hendra (HeV) viruses are emerging zoonotic paramyxoviruses that cause encephalitis in humans, with fatality rates of up to 75%. We designed a new high-throughput screening (HTS) assay for inhibitors infection based on envelope glycoprotein pseudotypes. The simulates multicycle replication thus identifies target several stages the viral life cycle, but it still can be carried out under biosafety level 2 (BSL-2) conditions. These features permit screen antivirals select agents...
Background. The first step in infection by human parainfluenza viruses (HPIVs) is binding to the surface of respiratory epithelial cells via interaction between viral receptor-binding molecules and sialic acid-containing receptors. DAS181, a recombinant sialidase protein containing catalytic domain Actinomyces viscosus sialidase, removes cell acid, we proposed that it would inhibit HPIV infection. Methods. Depletion acid receptors DAS181 was evaluated lectin-binding assays. Anti-HPIV...
ABSTRACT Three discrete activities of the paramyxovirus hemagglutinin-neuraminidase (HN) protein, receptor binding, cleaving (neuraminidase), and triggering fusion each affect promotion viral entry. For human parainfluenza virus type 3 (HPIV3), effects specific mutations that alter these functions receptor-binding protein have been well characterized using cultured monolayer cells, which identified steps are potentially relevant to pathogenesis. In present study, proposed mechanisms...
Fusion between the viral and target cell membranes is an obligatory step for infectivity of all enveloped virus, blocking this process a clinically validated therapeutic strategy. Viral fusion driven by specialized proteins which, although specific to each act through common mechanism, formation complex two heptad repeat (HR) regions. The HR regions are initially separated in intermediate termed "prehairpin", which bridges membranes, then fold onto other form 6-helical bundle (6HB), driving...
Measles virus (MV) infection causes an acute childhood disease that can include of the central nervous system and rarely progress to severe neurological for which there is no specific treatment. We generated potent antiviral peptide inhibitors MV entry spreading MV-induced cell fusion. Dimers MV-specific peptides derived from C-terminal heptad repeat region fusion protein, conjugated cholesterol, efficiently protect SLAM transgenic mice fatal infection. Fusion hold promise prophylaxis in...