Antiviral lectin Q-Griffithsin suppresses fungal infection in murine models of vaginal candidiasis.

Resistance to antifungal agents in vulvovaginal candidiasis has resulted in increasing morbidity among women globally. It is therefore crucial that new antimycotic agents are developed to counter this rising challenge. Q-Griffithsin (Q-GRFT) is a red algal lectin, manufactured in .

Serological assessment of SARS-CoV-2 infection during the first wave of the pandemic in Louisville Kentucky.

Serological assays intended for diagnosis, sero-epidemiologic assessment, and measurement of protective antibody titers upon infection or vaccination are essential for managing the SARS-CoV-2 pandemic. Serological assays measuring the antibody responses against SARS-CoV-2 antigens are readily available. However, some lack appropriate characteristics to accurately measure SARS-CoV-2 antibodies titers and neutralization.

Novel Antifungal Activity of Q-Griffithsin, a Broad-Spectrum Antiviral Lectin.

There is a rising global incidence of strains with high levels of resistance to fluconazole and other antifungal drugs, hence the need for novel antifungal treatment strategies. Here, we describe the first evidence of antifungal activity of Q-Griffithsin (Q-GRFT), a recombinant oxidation-resistant variant of Griffithsin, a marine red algal lectin with broad-spectrum antiviral activity. We demonstrated that Q-GRFT binds to α-mannan in the Candida albicans cell wall.

Preformulation Characterization of Griffithsin, a Biopharmaceutical Candidate for HIV Prevention.

Griffithsin (GRFT) has shown potent anti-HIV activity, and it is being developed as a drug candidate for HIV prevention. Successful implementation requires thorough understanding of its preformulation characterization. In this work, preformulation assessments were conducted to characterize GRFT and identify its degradation pathways under selected conditions of temperature, light, pH, shear, ionic strength, and oxidation.

In vitro Study on Synergistic Interactions Between Free and Encapsulated Q-Griffithsin and Antiretrovirals Against HIV-1 Infection.

Introduction: Human immunodeficiency virus (HIV) remains a persistent global challenge, impacting 38 million people worldwide. Antiretrovirals (ARVs) including tenofovir (TFV), raltegravir (RAL), and dapivirine (DAP) have been developed to prevent and treat HIV-1 via different mechanisms of action. In parallel, a promising biological candidate, griffithsin (GRFT), has demonstrated outstanding preclinical safety and potency against HIV-1.

Stability of plasmid and viral banks supporting the cGMP manufacture of Q-Griffithsin from a TMV-based viral vector.

The "whole genome" TMV-based expression system, Geneware®, was used in the cGMP production of the plant-made pharmaceutical Q-Griffithsin and demonstrates stable expression for up to a two-year period. Virion and plasmid banks which contained viral cDNA and a Q-Griffithsin sequence were able to produce >200 g of Q-Griffithsin. Data assessing the quality and stability of the product banks were measured through functional assessments of visual symptomology and product expression.

In Preparation for Outdoor Pharming: Griffithsin Can Be Expressed in and Retains Activity After Storage as Silage.

Griffithsin is an algae-derived lectin with strong anti-viral activity against HIV and a positive safety profile. Multiple clinical studies are investigating griffithsin's utility as topical HIV microbicide. HIV microbicides are an extremely cost-sensitive market and plant-based griffithsin protein expression has the potential to meet those demands.

Rapid-Release Griffithsin Fibers for Dual Prevention of HSV-2 and HIV-1 Infections.

The biologic griffithsin (GRFT) has recently emerged as a candidate to safely prevent sexually transmitted infections (STIs), including human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus 2 (HSV-2). However, to date, there are few delivery platforms that are available to effectively deliver biologics to the female reproductive tract (FRT). The goal of this work was to evaluate rapid-release polyethylene oxide (PEO), polyvinyl alcohol (PVA), and polyvinylpyrrolidone (PVP) fibers that incorporate GRFT in (HIV-1 and HSV-2) and (HSV-2) infection models.

Viral respiratory infections: a cause of community-acquired pneumonia or a predisposing factor?

Purpose Of Review: A cause for community-acquired pneumonia (CAP) is only identified in ∼50% of cases. Nasopharyngeal PCR panels contain more viruses than previously. The problem then becomes determining the relevance of the organisms identified rather than figuring out which virus is present.

Griffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge.

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis and respiratory disease in humans. There is currently no approved therapeutic for human use against NiV infection. Griffithsin (GRFT) is high-mannose oligosaccharide binding lectin that has shown in vivo broad-spectrum activity against viruses, including severe acute respiratory syndrome coronavirus, human immunodeficiency virus 1, hepatitis C virus, and Japanese encephalitis virus.

Sustained-release Griffithsin nanoparticle-fiber composites against HIV-1 and HSV-2 infections.

Human immunodeficiency virus (HIV-1) and herpes simplex virus 2 (HSV-2) affect hundreds of millions of people worldwide. The antiviral lectin, Griffithsin (GRFT), has been shown to be both safe and efficacious against HSV-2 and HIV-1 infections in vivo. The goal of this work was to develop a multilayered nanoparticle (NP)-electrospun fiber (EF) composite to provide sustained-release of GRFT, and to examine its safety and efficacy in a murine model of lethal HSV-2 infection.

Technoeconomic Modeling of Plant-Based Griffithsin Manufacturing.

Griffithsin is a marine algal lectin that exhibits broad-spectrum antiviral activity by binding oligomannose glycans on viral envelope glycoproteins, including those found in HIV-1, HSV-2, SARS, HCV and other enveloped viruses. An efficient, scalable and cost-effective manufacturing process for Griffithsin is essential for the adoption of this drug in human antiviral prophylaxis and therapy, particularly in cost-sensitive indications such as topical microbicides for HIV-1 prevention. The production of certain classes of recombinant biologics in plants can offer scalability, cost and environmental impact advantages over traditional biomanufacturing platforms.

Bulk production of the antiviral lectin griffithsin.

Application of plant-based protein expression systems for bulk production of recombinant protein pharmaceuticals is building momentum. There are considerable regulatory challenges to consider in commercialization of plant-made pharmaceuticals (PMPs), some of which are inherent to plant-production systems and others that are common with other production systems, but are new to PMPs because of the youth of the industry. In this review, we discuss our recent and ongoing experience with bulk production of the HIV microbicide candidate, griffithsin (GRFT), utilizing plant-based transient protein expression, with specific focus on areas relevant to commercial manufacturing of bulk GRFT active pharmaceutical ingredient (API).

Improving the large scale purification of the HIV microbicide, griffithsin.

Background: Griffithsin is a broad spectrum antiviral lectin that inhibits viral entry and maturation processes through binding clusters of oligomannose glycans on viral envelope glycoproteins. An efficient, scaleable manufacturing process for griffithsin active pharmaceutical ingredient (API) is essential for particularly cost-sensitive products such as griffithsin -based topical microbicides for HIV-1 prevention in resource poor settings. Our previously published purification method used ceramic filtration followed by two chromatography steps, resulting in a protein recovery of 30%.

Prefrontal cortical recordings with biomorphic MEAs reveal complex columnar-laminar microcircuits for BCI/BMI implementation.

The mammalian prefrontal cortex known as the seat of high brain functions uses a six layer distribution of minicolumnar neurons to coordinate the integration of sensory information and the selection of relevant signals for goal driven behavior. To reveal the complex functionality of these columnar microcircuits we employed simultaneous recordings with several configurations of biomorphic microelectrode arrays (MEAs) within cortical layers in adjacent minicolumns, in four nohuman primates (NHPs) performing a delayed match-to-sample (DMS) visual discrimination task. We examined: (1) the functionality of inter-laminar, and inter-columnar interactions between pairs of cells in the same or different minicolumns by use of normalized cross-correlation histograms (CCH), (2) the modulation of glutamate concentration in layer 2/3, and (3) the potential interactions within these microcircuits.

Dynamic changes in dopamine neuron function after DNSP-11 treatment: effects in vivo and increased ERK 1/2 phosphorylation in vitro.

Glial cell-line derived neurotrophic factor (GDNF) has demonstrated robust effects on dopamine (DA) neuron function and survival. A post-translational processing model of the human GDNF proprotein theorizes the formation of smaller, amidated peptide(s) from the proregion that exhibit neurobiological function, including an 11-amino-acid peptide named dopamine neuron stimulating peptide-11 (DNSP-11). A single treatment of DNSP-11 was delivered to the substantia nigra in the rat to investigate effects on DA-neuron function.

Conformal ceramic electrodes that record glutamate release and corresponding neural activity in primate prefrontal cortex.

Conformal ceramic electrodes utilized in prior recordings of nonhuman primate prefrontal cortical layer 2/3 and layer 5 neurons were used in this study to record tonic glutamate concentration and transient release in layer 2/3 PFC. Tonic glutamate concentration increased in the Match (decision) phase of a visual delayed-match-to-sample (DMS) task, while increased transient glutamate release occurred in the Sample (encoding) phase of the task. Further, spatial vs.

Closing the loop in primate prefrontal cortex: inter-laminar processing.

Prefrontal cortical (PFC) activity in the primate brain emerging from minicolumnar microcircuits plays a critical role in cognitive processes dealing with executive control of behavior. However, the specific operations of columnar laminar processing in prefrontal cortex (PFC) are not completely understood. Here we show via implementation of unique microanatomical recording and stimulating arrays, that minicolumns in PFC are involved in the executive control of behavior in rhesus macaque nonhuman primates (NHPs) performing a delayed-match-to-sample (DMS) task.