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Viral Infection

1048

SARS-CoV-2 presence in recreational seawater and evaluation of intestine permeability: experimental evidence of low impact on public health

Introduction: Coastal seawater pollution poses a public health risk due to the potential ingestion of contaminated water during recreational activities. Wastewater-based epidemiology has revealed the abundant presence of SARS-CoV-2 in seawater emitted from wastewater outlets. The objective of this research was to investigate the impact of seawater on SARS-CoV-2 infectivity to assess the safety of […]
1005

Single-cell analysis of Kaposi’s sarcoma-associated herpesvirus infection in three-dimensional air-liquid interface culture model

The oral cavity is the major site for transmission of Kaposi’s sarcoma-associated herpesvirus (KSHV), but how KSHV establishes infection and replication in the oral epithelia remains unclear. Here, we report a KSHV spontaneous lytic replication model using fully differentiated, three dimensional (3D) oral epithelial organoids at an air-liquid interface (ALI). This model revealed that KSHV […]
967

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 […]
943

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 […]
942

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 […]
938

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 […]
932

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 […]
928

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 […]
927

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 […]
924

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 […]
923

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 […]
922

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 […]
918

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 […]
913

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 […]
907

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 […]
906

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 […]
902

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 […]
899

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) […]
898

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; […]
888

Fecal Components Modulate Human Astrovirus Infectivity in Cells and Reconstituted Intestinal Tissues

Human astroviruses (HAstV) are among the most common causative agents of viral gastroenteritis, especially in children, and extraintestinal manifestations have also been described. These viruses are transmitted by the fecal-oral route, implying that stool composition and the gut microbiota may impact their ability to remain infectious. For some enteric viruses, individual bacterial envelope components and […]
806

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 […]