Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 18,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS.
View Article and Find Full Text PDFUnlabelled: Heartland virus (HRTV) is an emerging tick-borne bandavirus that causes a febrile illness of varying severity in humans, with cases reported in eastern and midwestern regions of the United States. No vaccines or approved therapies are available to prevent or treat HRTV disease. Here, we describe the genetic changes, natural history of disease, and pathogenesis of a mouse-adapted HRTV (MA-HRTV) that is uniformly lethal in 7- to 8-week-old AG129 mice at low challenge doses.
View Article and Find Full Text PDFThe zoonotic Rift Valley fever virus (RVFV) can cause severe disease in humans and has pandemic potential, yet no approved vaccine or therapy exists. Here we describe a dual-mechanism human monoclonal antibody (mAb) combination against RVFV that is effective at minimal doses in a lethal mouse model of infection. We structurally analyze and characterize the binding mode of a prototypical potent Gn domain-A-binding antibody that blocks attachment and of an antibody that inhibits infection by abrogating the fusion process as previously determined.
View Article and Find Full Text PDFSeasonal influenza virus infections cause a substantial number of deaths each year. While zanamivir (ZAN) is efficacious against oseltamivir-resistant influenza strains, the efficacy of the drug is limited by its route of administration, oral inhalation. Herein, we present the development of a hydrogel-forming microneedle array (MA) in combination with ZAN reservoirs for treating seasonal influenza.
View Article and Find Full Text PDFBackground: Persons with stroke often have difficulty achieving target heart rate (HR) during graded exercise testing (GXT), which is known to limit test sensitivity for detecting clinically relevant cardiac conditions. A novel Recumbent Stepper 3-minute (RS 3Min) "all out" test may increase sensitivity of stress testing after stroke.
Objective: To determine the feasibility of adding the RS 3Min test after GXT among persons after stroke.
Importance: Statins reduce the risk of major adverse cardiovascular events, but less than one-half of individuals in America who meet guideline criteria for a statin are actively prescribed this medication.
Objective: To evaluate whether nudges to clinicians, patients, or both increase initiation of statin prescribing during primary care visits.
Design, Setting, And Participants: This cluster randomized clinical trial evaluated statin prescribing of 158 clinicians from 28 primary care practices including 4131 patients.
BMC Oral Health
February 2022
Background: Healthcare professionals, especially dentists and dental hygienists, are at increased risk for contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through air-borne particles and splatter. This study assessed the in vitro virucidal activity of 0.5% (w/v) povidone-iodine (PVP-I) oral rinse against SARS-CoV-2 to demonstrate its utility as a professional oral rinse.
View Article and Find Full Text PDFSeveral arenaviruses, including Lassa and Lujo viruses in Africa and five New World arenavirus (NWA) species in the Americas, cause life-threatening viral hemorrhagic fevers. In the absence of licensed antiviral therapies, these viruses pose a significant public health risk. The envelope glycoprotein complex (GPC) mediates arenavirus entry through a pH-dependent fusion of the viral and host endosomal membranes.
View Article and Find Full Text PDFBroadly reactive antibodies targeting the influenza A virus hemagglutinin (HA) head domain are thought to be rare and to require extensive somatic mutations or unusual structural features to achieve breadth against divergent HA subtypes. Here we describe common genetic and structural features of protective human antibodies from several individuals recognizing the trimer interface (TI) of the influenza A HA head, a recently identified site of vulnerability. We examined the sequence of TI-reactive antibodies, determined crystal structures for TI antibody-antigen complexes, and analyzed the contact residues of the antibodies on HA to discover common genetic and structural features of TI antibodies.
View Article and Find Full Text PDFRift Valley fever virus (RVFV), an emerging arboviral and zoonotic bunyavirus, causes severe disease in livestock and humans. Here, we report the isolation of a panel of monoclonal antibodies (mAbs) from the B cells of immune individuals following natural infection in Kenya or immunization with MP-12 vaccine. The B cell responses of individuals who were vaccinated or naturally infected recognized similar epitopes on both Gc and Gn proteins.
View Article and Find Full Text PDFThe 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 highly efficacious and well tolerated in hepatitis C virus (HCV)-infected subjects.
View Article and Find Full Text PDFIn the United States, pre-exposure prophylaxis (PrEP) uptake among eligible cisgender women has been slow, despite the availability of oral PrEP since 2012. Although women make up nearly 20% of those living with HIV, there are currently few PrEP uptake interventions for cisgender women at elevated risk for acquiring HIV. Here we describe the process used to design and pre-pilot test Just4Us, a theory-based behavioral intervention to promote PrEP initiation and adherence among PrEP-eligible cisgender women.
View Article and Find Full Text PDFPT150 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; thus, it was now tested against SARS-CoV-2 in human bronchial epithelial lining cells and showed effective 90% inhibitory antiviral concentration (EC90) of 5.
View Article and Find Full Text PDFImportance: Statin therapy is underused for many patients who could benefit.
Objective: To evaluate the effect of passive choice and active choice interventions in the electronic health record (EHR) to promote guideline-directed statin therapy.
Design, Setting, And Participants: Three-arm randomized clinical trial with a 6-month preintervention period and 6-month intervention.
Background The initial global outbreak of the novel coronavirus disease 2019 (COVID-2019) pandemic, which is responsible for the severe acute respiratory syndrome 2 (SARS-CoV-2), shares similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) and behaves similarly to influenza with a high intranasal viral load. The genome sequence of COVID-19 opened the opportunity for multiple in vitro and clinical trials, but we still do not have a clear path to treatment. Chlorpheniramine maleate (CPM) is a safe and effective antihistamine with potent antiviral activity against various strains of influenza A/B, thus suggesting that CPM has broad antiviral activity.
View Article and Find Full Text PDFIntroduction: Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the global pandemic of coronavirus disease 2019 (COVID-19). From the first reported cases in December 2019, the virus has spread to over 4 million people worldwide. Human-to-human transmission occurs mainly through the aerosolization of respiratory droplets.
View Article and Find Full Text PDFJAMA Otolaryngol Head Neck Surg
November 2020
Purpose: To evaluate the in vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with hydrogen peroxide (H O ) and povidone-iodine (PVP-I) oral antiseptic rinses at clinically recommended concentrations and contact times.
Materials And Methods: SARS-CoV-2, USA-WA1/2020 strain virus stock was prepared prior to testing by growing in Vero 76 cells. The culture media for prepared virus stock was minimum essential medium (MEM) with 2% fetal bovine serum (FBS) and 50 µg/mL gentamicin.