Efficient assay for evaluating drug efficacy and synergy against emerging SARS-CoV-2 strains.

Novel and repurposed antiviral drugs are available for the treatment of coronavirus disease 2019 (COVID-19). However, antiviral combinations may be more potent and lead to faster viral clearance, but the methods for screening antiviral combinations against respiratory viruses are not well established and labor-intensive. Here, we describe a time-efficient (72-96 h) and simple drug-sensitivity assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using standard 96-well plates.

A one-step method for generating antimicrobial nanofibre meshes coaxial electrospinning.

Respiratory diseases, including influenza, infectious pneumonia, and severe acute respiratory syndrome (SARS), are a leading cause of morbidity and mortality worldwide. The recent COVID-19 pandemic claimed over 6.9 million lives globally.

It's a Start: An Online, On-Demand LGBTQ+ Mental Health Training Session for Providers Nationwide.

Objective: The purpose of this study was to determine whether an online, on-demand, and publicly accessible mental health training session on care for lesbian, gay, bisexual, transgender, queer, and all sexual-diverse and gender-diverse (LGBTQ+) individuals could improve providers' preparedness, attitudes, and knowledge regarding care for LGBTQ+ patients.

Methods: Between January and June 2022, participating mental health providers completed the Lesbian, Gay, Bisexual, and Transgender Development of Clinical Skills Scale (LGBT-DOCSS) before and after training.

Results: Participants (N=322) represented various mental health specialties and all U.

BMI1 Transduction of Human Airway Epithelial Cells for Expansion of Proliferation and Differentiation.

Air-liquid interface (ALI)-cultured cells are widely used as in vitro models of the human respiratory airway in studies of pulmonary physiology, disease, and therapies. However, the primary basal cells required to establish the ALI cultures generally lose their ability to differentiate by the second or third passage, requiring a fresh batch, which can be limiting, particularly from donors with rare genotypes or in studies where gene modification or editing is required. We have developed a method that preserves the ability to expand primary cells and maintain their capacity to differentiate by lentiviral transduction with BMI1.

Correlation of SARS-CoV-2 Neutralization with Antibody Levels in Vaccinated Individuals.

Neutralizing antibody titers are an important measurement of the effectiveness of vaccination against SARS-CoV-2. Our laboratory has set out to further verify the functionality of these antibodies by measuring the neutralization capacity of patient samples against infectious SARS-CoV-2. Samples from patients from Western New York who had been vaccinated with the original Moderna and Pfizer vaccines (two doses) were tested for neutralization of both Delta (B.

Using Structured Decision Making to Evaluate Wetland Restoration Opportunities in the Chesapeake Bay Watershed.

Wetland restoration is an important water quality and climate resilience strategy. Wetland restoration rarely considers tradeoffs at large spatial and temporal scales, which limits capacity to aid decision makers. High resolution data can reveal hundreds to thousands of possible restoration options across a landscape, but guidance for setting restoration targets at these scales is limited.

"I do the she and her": A qualitative exploration of HIV care providers' considerations of trans women in gender-specific HIV care.

Objectives: Women of all genders, including cisgender (cis) and transgender (trans) women, experience social and structural drivers of HIV inequities and pervasive barriers to HIV care. Yet, little is known about how HIV care providers address gender diversity in health care. Through a critical feminist lens informed by intersectionality theory, medical anthropology, and critical sociology, we explored (1) how do HIV care providers describe women living with HIV's care needs and barriers; (2) what are their perspectives on optimal HIV care for women; and (3) to what extent do these conceptualizations include/exclude trans women.

Cryptococcus neoformans Coinfection Dampens the TNF-α Response in HIV-1-Infected Human THP-1 Macrophages.

is a devastating opportunistic fungal pathogen. It mostly impacts people in an immunocompromised state, such as people living with HIV/AIDS and following organ transplantation. Macrophages, in addition to being a major cellular reservoir of HIV-1, represent a unique niche in which both and HIV-1 can coinhabit in the course of natural infection.

Identification of Zika Virus Inhibitors Using Homology Modeling and Similarity-Based Screening to Target Glycoprotein E.

The World Health Organization has designated Zika virus (ZIKV) as a dangerous, mosquito-borne pathogen that can cause severe developmental defects. The primary goal of this work was identification of small molecules as potential ZIKV inhibitors that target the viral envelope glycoprotein (ZIKV E) involved in membrane fusion and viral entry. A homology model of ZIKV E containing the small molecule β-octyl glucoside (BOG) was constructed, on the basis of an analogous X-ray structure from dengue virus, and >4 million commercially available compounds were computationally screened using the program DOCK6.

Identification of Ebola Virus Inhibitors Targeting GP2 Using Principles of Molecular Mimicry.

A key step in the Ebola virus (EBOV) replication cycle involves conformational changes in viral glycoprotein 2 (GP2) which facilitate host-viral membrane fusion and subsequent release of the viral genome. Ebola GP2 plays a critical role in virus entry and has similarities in mechanism and structure to the HIV gp41 protein for which inhibitors have been successfully developed. In this work, a putative binding pocket for the C-terminal heptad repeat in the N-terminal heptad repeat trimer was targeted for identification of small molecules that arrest EBOV-host membrane fusion.

Inhibition of HIV Entry by Targeting the Envelope Transmembrane Subunit gp41.

Background: The transmembrane subunit of the HIV envelope protein, gp41 is a vulnerable target to inhibit HIV entry. There is one fusion inhibitor T20 (brand name: Fuzeon, generic name: enfuvirtide) available by prescription. However, it has several drawbacks such as a high level of development of drug resistance, a short-half life in vivo, rapid renal clearance, low oral bioavailability, and it is only used as a salvage therapy.

Radiofrequency Ablation for Liver Cancer.

Interventional ablative technologies aided by imaging techniques such as ultrasonography, computed tomography, and magnetic resonance imaging have been crucial in managing patients with primary liver cancer and liver metastases over the past 20 years. Several ablative technologies have been used to treat liver cancer; however, radiofrequency ablation (RFA) has emerged as the most common ablative therapy for hepatic lesions, both in the United States and globally. RFA is the treatment of choice for patients who cannot have surgical resection of the liver.

Small molecule inhibitors of HIVgp41 N-heptad repeat trimer formation.

Identification of mechanistically novel anti-HIV fusion inhibitors was accomplished using a computer-aided structure-based design approach with the goal of blocking the formation of the N-heptad repeat (NHR) trimer of the viral protein gp41. A virtual screening strategy that included per-residue interaction patterns (footprints) was employed to identify small molecules compatible with putative binding pockets at the internal interface of the NHR helices at the core native viral six-helix bundle. From a screen of ∼2.

Functionalization of cobalt porphyrin-phospholipid bilayers with his-tagged ligands and antigens.

Methods to attach polypeptides to lipid bilayers are often indirect and ineffective, and can represent a substantial bottleneck in the formation of functionalized lipid-based materials. Although the polyhistidine tag (his-tag) has been transformative in its simplicity and efficacy in binding to immobilized metals, the successful application of this approach has been challenging in physiological settings. Here we show that lipid bilayers containing porphyrin-phospholipid conjugates that are chelated with cobalt, but not with other metals, can effectively capture his-tagged proteins and peptides.

The membrane proximal external regions of gp41 from HIV-1 strains HXB2 and JRFL have different sensitivities to alanine mutation.

The transmembrane subunit (gp41) of the HIV envelope protein complex (Env) mediates the viral fusion step of HIV entry. The membrane proximal external region (MPER), one of the functional domains of gp41, has been the focus of a great deal of research because it is a target for neutralizing antibodies. In this study, we examined 23 amino acid residues in the MPER (660-683) in both a CXCR4 coreceptor-utilizing strain (HXB2) and a CCR5-utilizing strain (JRFL) by alanine scanning mutagenesis.

Hospital-acquired methicillin-resistant Staphylococcus aureus: status and trends.

Methicillin-resistant Staphylococcus aureus (MRSA) has been a pathogen of serious concern to both the health care and public health communities since the 1960s. This article focuses on the most serious strains of MRSA, hospital-acquired/health care-associated MRSA. Signs and symptoms of MRSA infection are described, in addition to the modes of transmission, laboratory techniques for identifying MRSA, and treatment options.

Significant differences in cell-cell fusion and viral entry between strains revealed by scanning mutagenesis of the C-heptad repeat of HIV gp41.

The transmembrane subunit, gp41, of the HIV envelope mediates the viral fusion step of entry into the host cell. The protein consists of an extracellular domain, a transmembrane domain, and a cytoplasmic tail. The extracellular domain contains a fusion peptide, an N-terminal heptad repeat, a loop region, a C-terminal heptad repeat (CHR), and a membrane-proximal external region.

Mapping the Vif-A3G interaction using peptide arrays: a basis for anti-HIV lead peptides.

Human apolipoprotein-B mRNA-editing catalytic polypeptide-like 3G (A3G) is a cytidine deaminase that restricts retroviruses, endogenous retro-elements and DNA viruses. A3G plays a key role in the anti-HIV-1 innate cellular immunity. The HIV-1 Vif protein counteracts A3G mainly by leading A3G towards the proteosomal machinery and by direct inhibition of its enzymatic activity.

Targeting HIV-1 gp41-induced fusion and pathogenesis for anti-viral therapy.

HIV gp41 is a metastable protein whose native conformation is maintained in the form of a heterodimer with gp120. The non-covalently associated gp41/gp120 complex forms a trimer on the virus surface. As gp120 engages with HIV's receptor, CD4, and coreceptor, CXCR4 or CCR5, gp41 undergoes several conformational changes resulting in fusion between the viral and cellular membranes.

Development of non-natural flavanones as antimicrobial agents.

With growing concerns over multidrug resistance microorganisms, particularly strains of bacteria and fungi, evolving to become resistant to the antimicrobial agents used against them, the identification of new molecular targets becomes paramount for novel treatment options. Recently, the use of new treatments containing multiple active ingredients has been shown to increase the effectiveness of existing molecules for some infections, often with these added compounds enabling the transport of a toxic molecule into the infecting species. Flavonoids are among the most abundant plant secondary metabolites and have been shown to have natural abilities as microbial deterrents and anti-infection agents in plants.

Inhibition of HIV entry by extracellular glucuronoxylomannan of Cryptococcus neoformans.

Cryptococcosis, caused by Cryptococcus neoformans, is the most common opportunistic fungal disease in HIV/AIDS patients. The prognosis of AIDS patients with Cryptococcus infection is very poor. One of the major characteristics in cryptococcosis patients is the presence of high concentrations of the cryptococcal capsule polysaccharide (CCP) in the serum and cerebrospinal fluid.

Permanent inhibition of viral entry by covalent entrapment of HIV gp41 on the virus surface.

HIV entry occurs by concerted conformational changes in the envelope protein complex on the surface of the virus. This complex is made up of a trimer of heterodimers of two subunits: surface subunit, gp120, and transmembrane subunit, gp41. Conformational changes in the envelope complex allow gp41 to mediate membrane fusion leading to exposure of two gp41 regions: N-heptad repeat (NHR) and C-heptad repeat (CHR).