Infectious disease research

Surfactant Protein D Reverses the Gene Signature of Transepithelial HIV-1 Passage and Restricts the Viral Transfer Across the Vaginal Barrier

Effective prophylactic strategy against the current epidemic of sexually transmitted HIV-1 infection requires understanding of the innate gatekeeping mechanisms at the genital mucosa. Surfactant protein D (SP-D), a member of the collectin family of proteins naturally present in the vaginal tract, is a potential HIV-1 entry inhibitor at the cellular level. Human EpiVaginal tissues compartmentalized […]

Antiviral activity of EIDD-1931 and Remdesivir against SARS-CoV-2 variants in a 3D mucociliary tissue models consisting of normal human-derived tracheal/bronchial (EpiAirway) and nasal (EpiNasal) epithelial cells

In vitro assays are an important early step to determine the potential antiviral activity of novel compounds. The antiviral efficacy of compounds is often evaluated in immortalized cell lines, which offer the advantage of cost effectiveness, ease of use, and reproducibility. However, these monolayer cell lines are not always predictive for cytotoxicity or in vivo […]

Replication and antiviral activity of MERS and SARS-CoV-2 variants in a highly specialized 3D mucociliary tissue model consisting of normal human-derived tracheal/bronchial epithelial cells

In vitro assays are an important early step to determine the potential antiviral activity of novel compounds. The antiviral efficacy of compounds is often evaluated in immortalized cell lines, which offer the advantage of cost effectiveness, ease of use, and reproducibility. However, these monolayer cell lines are not always predictive for cytotoxicity or in vivo […]

Enisamium is an inhibitor of the SARS-CoV-2 RNA polymerase and shows improvement of recovery in COVID-19 patients in an interim analysis of a clinical trial

Pandemic SARS-CoV-2 causes a mild to severe respiratory disease called Coronavirus Disease 2019 (COVID-19). Control of SARS-CoV-2 spread will depend on vaccine-induced or naturally acquired protective herd immunity. Until then, antiviral strategies are needed to manage COVID-19, but approved antiviral treatments, such as remdesivir, can only be delivered intravenously. Enisamium (laboratory code FAV00A, trade name […]

AT-527, a Double Prodrug of a Guanosine Nucleotide Analog, Is a Potent Inhibitor of SARS-CoV-2 In Vitro and a Promising Oral Antiviral for Treatment of COVID-19

The impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, is global and unprecedented. Although remdesivir has recently been approved by the FDA to treat SARS-CoV-2 infection, no oral antiviral is available for outpatient treatment. AT-527, an orally administered double prodrug of a guanosine nucleotide analog, was previously shown to be […]

Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant

SARS-CoV-2 Delta variant has rapidly replaced the Alpha variant around the world. The mechanism that drives this global replacement has not been defined. Here we report that Delta spike mutation P681R plays a key role in the Alpha-to-Delta variant replacement. In a replication competition assay, Delta SARS-CoV-2 efficiently outcompeted the Alpha variant in human lung […]

Modeling SARS-CoV-2 and Influenza Infections and Antiviral Treatments in Human Lung 2 Epithelial Tissue Equivalents

Sever acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the third coronavirus in less than 20 years to spillover from an animal reservoir and cause severe disease in humans. High impact respiratory viruses such a pathogenic beta-coronaviruses and influenza viruses, as well as other emerging respiratory viruses, pose an ongoing global health threat to humans. There is […]

Multidose evaluation of 6,710 drug repurposing library identifies potent SARS-CoV-2 infection inhibitors In Vitro and In Vivo

The SARS-CoV-2 pandemic has caused widespread illness, loss of life, and socioeconomic disruption that is unlikely to resolve until vaccines are widely adopted, and effective therapeutic treatments become established. Here, a well curated and annotated library of 6710 clinical and preclinical molecules, covering diverse chemical scaffolds and known host targets was evaluated for inhibition of […]

Potent Antiviral Activity against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids

Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of antiviral drugs involves the identification of a unique viral target, followed by the design of an agent […]

The N501Y spike substitution enhances SARS-CoV-2 transmission

Beginning in the summer of 2020, a variant of SARS-CoV-2, the cause of the COVID-19 pandemic, emerged in the United Kingdom (UK). This B.1.1.7 variant increased rapidly in prevalence among sequenced strains, attributed to an increase in infection and/or transmission efficiency. The UK variant has 19 nonsynonymous mutations across its viral genome including 8 substitutions […]

Oral Hsp90 inhibitor, SNX-5422, attenuates SARS-CoV-2 replication and dampens 2 inflammation in airway cells.

Currently available SARS-CoV-2 therapeutics are targeted towards moderately to severely ill patients and require intravenous infusions, with limited options for exposed or infected patients with no or mild symptoms. While vaccines have demonstrated protective efficacy, vaccine hesitancy and logistical distribution challenges will delay their ability to end the pandemic. Hence, there is a need for […]

A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication

Except remdesivir, no specific antivirals for SARS-CoV-2 infection are currently available. Here, we characterize two small-molecule-compounds, named GRL-1720 and 5h, containing an indoline and indole moiety, respectively, which target the SARS-CoV-2 main protease (Mpro). We use VeroE6 cell-based assays with RNA-qPCR, cytopathic assays, and immunocytochemistry and show both compounds to block the infectivity of SARS-CoV-2 […]

The SARS-CoV‑2 Cytopathic Effect Is Blocked by Lysosome Alkalizing Small Molecules

Understanding the SARS-CoV-2 virus’ pathways of infection, virus−host−protein interactions, and mechanisms of virus-induced cytopathic effects will greatly aid in the discovery and design of new therapeutics to treat COVID-19. Chloroquine and hydroxychloroquine, extensively explored as clinical agents for COVID-19, have multiple cellular effects including alkalizing lysosomes and blocking autophagy as well as exhibiting dose-limiting toxicities […]

Influenza A Virus Infection of Human Respiratory Cells Induces Primary MicroRNA Expression*

The cellular response to virus infection is initiated by recognition of the invading pathogen and subsequent changes in gene expression mediated by both transcriptional and translational mechanisms. In addition to well established means of regulating antiviral gene expression, it has been demonstrated that RNA interference (RNAi) can play an important role in antiviral responses. Virus-derived […]

Prolonged infectious SARS-CoV-2 shedding from an asymptomatic immunocompromised cancer patient.

Long-term SARS-CoV-2 shedding was observed from the upper respiratory tract of a female immunocompromised patient with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Shedding of infectious SARS-CoV-2 was observed up to 70 days, and genomic and subgenomic RNA up to 105 days past initial diagnosis. The infection was not cleared after a first treatment with convalescent […]

Inhibition of Coronavirus Entry In Vitro and Ex Vivo by a Lipid Conjugated Peptide Derived from the SARS-CoV-2 Spike Glycoprotein HRC Domain

The emergence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of the 2019 coronavirus disease (COVID-19), has erupted into a global pandemic that has led to tens of millions of infections and hundreds of thousands of deaths worldwide. The development of therapeutics to treat infection or as prophylactics to halt viral […]

Spike mutation D614G alters SARS-CoV-2 fitness and neutralization susceptibility

A spike protein mutation D614G became dominant in SARS-CoV-2 during the COVID-19 pandemic. However, the mutational impact on viral spread and vaccine efficacy remains to be defined. Here we engineer the D614G mutation in the SARS-CoV-2 USA-WA1/2020 strain and characterize its effect on viral replication, pathogenesis, and antibody neutralization. The D614G mutation significantly enhances SARS-CoV-2 […]

In vivo antiviral host transcriptional response to SARS-CoV-2 by viral load, sex, and age

Despite limited genomic diversity, severe acute respiratory syndrome coronavirus 2 (SARSCoV-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 host response gene expression across infection status, viral load, age, and sex among shotgun RNA sequencing profiles of nasopharyngeal (NP) […]

PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2

PT150 is a clinical stage molecule, taken orally, with a strong safety profile having completed Phase 1 and Phase 2 clinical trials for its original use as an antidepressant. It has an active IND for COVID-19. Antiviral activities have been found for PT150 and other members of its class in a variety of virus families; […]

A series of in vitro and human studies of a novel lip cream formulation for protecting against environmental triggers of recurrent herpes labialis

Purpose: These studies describe the testing of a novel, daily-use lip cream designed for individuals with lips prone to recurrent herpes labialis (RHL) that protects against environmental triggers. Subjects and methods: In vitro occlusive and in vitro and in vivo photoprotection analyses, a characterization of normal vs dry lips, and a randomized, evaluator-blinded, clinical trial […]

Antiviral Activity of Ribavirin, 2’,3’-Dideoxicitidine, Pirodavir, Oseltamivir and Infergen™ against RSV, Adeno-2, Rhino-14, Influenza and HCoV-EMC Infection in Differentiated Normal Bronchial Epithelial (dNHBE) Cells

The antiviral activity of ribavirin, 2’,3’-ddC, pirodavir, oseltamivir and Infergen™ was evaluated against respiratory syncytial virus (RSV), adenovirus type 2, rhinovirus type 14, influenza, and human coronavirus HCoV-EMC in a highly differentiated, three-dimensional, ex vivo model of normal human bronchial (dNHBE) cells. Antiviral activity was measured by virus yield reduction assays 3-6 days after infection in the presence of […]

THE RETROCYCLIN ANALOGUE RC-101 PREVENTS HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 INFECTION OF A MODEL HUMAN CERVICOVAGINAL TISSUE CONSTRUCT.

This study by researchers at the University of Central Florida, University of Pittsburgh and UCLA School of Medicine demonstrated that Mattek’s EpiVaginal human vaginal-ectocervical tissue equivalent can be used to test the toxicity and efficacy of potential HIV-1 topical microbicides. Retrocyclins are cyclic antimicrobial peptides that exhibit potent activity towards a broad range of primary […]

HUMAN VAGINAL—ECTOCERVIAL TISSUE MODEL TO TEST THE IRRITATION POTENTIAL OF CONTRACEPTIVE AND VAGINAL-CARE PRODUCTS.

RANTES, GRO-α, TNF-α RELEASE FROM IN VITRO EPIDERMIS MODELS FOLLOWING TREATMENT OF STAPHLOCOCCAL ENTEROTOXIN A.

Human skin equivalent cultures are currently being investigated as in vitro models to predict the cytokine expression. The object of the research presented here is to evaluate the production of panel of immunomodulatory cytokines under the Staphylococcus infection and to determine the modulation of these cytokines following exposure to Staphylococcal enterotoxin in the Mattek EpiDerm […]

INFECTION OF HUMAN CYTOMEGALOVIRUS IN CULTURED HUMAN GINGIVAL TISSUE.

This study by researchers at UC Berkeley School of Public Health demonstrated that Mattek’s EpiGingival in vitro human tissue equivalent can be used to study human cytomegalovirus (HCMV) infection, and to screen antivirals that block viral replication and transmission in the oral cavity. Background: Human cytomegalovirus (HCMV) infection in the oral cavity plays an important […]

RECONSTRUCTED HUMAN VAGINAL-ECTOCERVICAL TISSUE MODELS.

Acquired immunodeficiency syndrome (AIDS) is now the fourth most common cause of death worldwide. In the last 20 years, more than 60 million people have been infected with the virus. By the end of 2002, an estimated 42 million people globally were living with HIV and the majority of new infections occurred in young adult […]

DIFFERENTIAL REGULATION OF â-DEFENSIN EXPRESSION IN HUMAN SKIN BY MICROBIAL STIMULI.

This study by researchers at UCLA’s David Geffen School of Medicine and Lund University (Sweden) demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent can be used to study the pathways that connect infection and inflammation with the induction of antimicrobial peptides in epithelia. In response to infection, epithelia mount an innate immune response […]

VAGINAL FORMULATION – HOW INNOCUOUS ARE THEY TO THE VAGINAL EPITHELIAL IMMUNE FUNCTION?

This study by researchers in the Harvard Medical School Dept. of Obstetrics and Gynecology demonstrated that Mattek’s EpiVaginal in vitro human cervico-vaginal tissue equivalent is an excellent tissue model for performing both immunoinflammatory characterization and safety assessment of vaginal products. Problem: The disruption of the epithelial barrier and activation of inflammatory pathways may lead to […]

GENETICALLY-ENGINEERED IL-10-SECRETING KERATINOCYTES CONDITION LANGERHANS CELLS TOWARDS A TOLERAGENIC PHENOTYPE.

This study by researchers at the State University of New York at Stony Brook demonstrated that Mattek’s Human Dendritic (Langerhans) Cells can be used to determine the influence of epithelial cells and cytokines on Langerhans cell activation and phenotype in response to microbial challenge. Epidermal Langerhans cells (Mattek Corp.), “sentinels” of the epithelium, undergo increased […]

EXPRESSION OF BETA-DEFENSINS IN RESPONSE TO HIV-1 IN AN ORAL TISSUE MODEL VS MONOLAYER CULTURES.

This study by researchers at the University of Washington and the Fred Hutchinson Cancer Research Center demonstrated that Mattek’s EpiOral in vitro human buccal (inner cheek) tissue equivalent can be used to investigate the expression of human beta-defensins (hBD) in response to exposure to HIV-1 virus. HIV transmission through the oral route is inefficient. Epithelial […]

IRRITATION TESTING OF CONTRACEPTIVE AND FEMININE-CARE PRODUCTS USING EPIVAGINAL, AN IN VITRO HUMAN VAGINAL-ECTOCERVICAL TISSUE MODEL.

ORGANOTYPIC ECTOCERVICO-VAGINAL TISSUE MODEL CONTAINING DENDRITIC CELLS.

Acquired immunodeficiency syndrome (AIDS) is now the fourth most common cause of death worldwide. In the last 20 years, more than 60 million people have been infected with the virus. By the end of 2001, an estimated 40 million people globally were living with HIV, and the majority of new infections occurred in young adult […]

RECONSTRUCTED, DIFFERENTIATED AIRWAY EPITHELIAL CULTURES TO MODEL RESPIRATORY INFECTION.

Normal human tracheal-bronchial epithelial cells (NHBE) have been cultured using serum free medium to form a three dimensional tissue-like structure, EpiAirway, that closely resembles the epithelial tissue of the respiratory tract. Histological cross-sections of both the in vitro tissue and a normal human bronchiole reveal a four layer, bipartite structure. Transmission electron microscopy revealed numerous […]

A HUMAN ORAL TISSUE MODEL TO EVALUATE TOXICITY AND ANTI-HIV ACTIVITY OF THE SPERMICIDE-MICROBICIDE, NONOXYNOL-9M.

This study by researchers at the University of Washington, the Fred Hutchinson Cancer Research Center and Mattek Corp. demonstrated that a new form of Mattek’s EpiOral full thickness human buccal tissue equivalent containing Langerhans Cells appears to be useful in evaluating pre-clinical microbicide toxicity and efficacy. Background: There is a need for a reproducible in […]

CATIONIC POLYPEPTIDES ARE REQUIRED FOR ANTI-HIV-1-ACTIVITY OF HUMAN VAGINAL FLUID.

This study by researchers at the University of Central Florida Biomolecular Science Center demonstrated that Mattek’s EpiVaginal human cervico-vaginal tissue equivalent is an excellent in vitro model for investigating HIV-1 infection via the mucosal surfaces of the vagina, as well as agents that may inhibit/prevent this route of HIV-1 infection, because of the tissue’s ability […]