Low Selectivity Indices of Ivermectin and Macrocyclic Lactones on SARS-CoV-2 Replication In Vitro

Ivermectin was first approved for human use as an endectocide in the 1980s. It remains one of the most important global health medicines in history and has recently been shown to exert in vitro activity against SARS-CoV-2. However, the macrocyclic lactone family of compounds has not previously been evaluated for activity against SARS-CoV-2. The present study aims at comparing their anti-viral activity in relevant human pulmonary cell lines in vitro. Here, in vitro antiviral activity of the avermectins (ivermectin and selamectin) and milbemycins (moxidectin and milbemycin oxime) were assessed against a clinical isolate from a CHU Montpellier patient infected with SARS-CoV-2 in 2020. Ivermectin, like the other macrocyclic lactones moxidectin, milbemycin oxime and selamectin, reduced SARS-CoV-2 replication in vitro (EC50 of 2–5 μM). Immunofluorescence assays with ivermectin and moxidectin showed a reduction in the number of infected and polynuclear cells, suggesting a drug action on viral cell fusion. However, cellular toxicity of the avermectins and milbemycins during infection showed a very low selectivity index of <10. Thus, none of these agents appears suitable for human use for its anti-SARS-CoV-2 activity per se, due to low selectivity index.

Rapid Protection from COVID-19 in Nonhuman Primates Vaccinated Intramuscularly but Not Intranasally with a Single Dose of a Vesicular Stomatitis Virus-Based Vaccine

The vesicular stomatitis virus (VSV) vaccine platform rose to fame in 2019, when a VSV-based Ebola virus (EBOV) vaccine was approved by the European Medicines Agency and the U.S. Food and Drug Administration for human use against the deadly disease.

Tobacco and Cannabis Debris Survey Protocol

Tobacco and cannabis product use can result in debris (a.k.a. litter) on the landscape, with implications to soil and water quality and thus potential impacts to ecosystems. More information is needed regarding how much debris exists on the landscape, such that the magnitude of potential associated environment problems can be quantified. Such information can raise awareness in the public about environmental hazards from tobacco and cannabis product use. The goal of this protocol is to quantify, via a timed survey approach, the tobacco and cannabis debris load (i.e. cigarette butts, cannabis or e-cigarette waste) at study sites. Multiple sites in a geographical location may be of interest for comparative analysis, for example sites used regularly by humans (e.g. trails, parking lots, around buildings, garbage cans) versus other sites that are suspected to have low human use. In any case, the same survey data sheet would be used (included with this protocol). Each survey will take 15 minutes per site to conduct. In the process of surveying, debris is collected and retained for later sorting, counting, and photographic documentation. The time to sort and count the collected debris will depend on the quantity and diversity of debris collected.

Plant-Based Vaccines: Antigen Design, Diversity, and Strategies for High Level Production

Vaccines for human use have conventionally been developed by the production of (1) microbial pathogens in eggs or mammalian cells that are then inactivated, or (2) by the production of pathogen proteins in mammalian and insect cells that are purified for vaccine formulation, as well as, more recently, (3) by using RNA or DNA fragments from pathogens. Another approach for recombinant antigen production in the last three decades has been the use of plants as biofactories. Only have few plant-produced vaccines been evaluated in clinical trials to fight against diseases, of which COVID-19 vaccines are the most recent to be FDA approved. In silico tools have accelerated vaccine design, which, combined with transitory antigen expression in plants, has led to the testing of promising prototypes in pre-clinical and clinical trials. Therefore, this review deals with a description of immunoinformatic tools and plant genetic engineering technologies used for antigen design (virus-like particles (VLP), subunit vaccines, VLP chimeras) and the main strategies for high antigen production levels. These key topics for plant-made vaccine development are discussed and perspectives are provided.

High concentrations of pharmaceuticals emerging as a threat to Himalayan water sustainability

The sixth UN Sustainable Development Goal, Clean Water and Sanitation, directly underpins other goals of Health, Life in Water and Sustainable Cities. We highlight that poor sanitation, exemplified through some of the highest concentrations of pharmaceuticals ever detected in rivers, will amplify societal and environmental stress where climate-induced reductions in flow are predicted. Rapidly growing urban centres with inadequate water treatment works will need to prioritise water quality improvement before supply reductions become a reality. For 23 river locations within Kathmandu City and the Annapurna region, Nepal, we show the presence of 28 of 35 monitored human-use pharmaceuticals. Concentrations of antibiotics measured in this sampling campaign in both Kathmandu City (sulfamethazine, metronidazole and ciprofloxacin) and rural locations (ciprofloxacin) are in excess of predicted no effect concentrations, suggesting these sites are at risk of proliferating antimicrobial resistance as well as affecting other ecotoxicological endpoints. It is anticipated that climate-induced reductions in flow combined with contaminated river systems will amplify future societal and environmental stress.

Protection of Mice against Experimental Cryptococcosis by Synthesized Peptides Delivered in Glucan Particles

Cryptococcosis, due to infection by fungi of the Cryptococcus neoformans species complex, is responsible for substantial morbidity and mortality in immunocompromised persons, particularly those with AIDS. Cryptococcal vaccines are a public health priority yet are not available for human use.

THC and CBD Fingerprinting of an Elite Cannabis Collection from Iran: Quantifying Diversity to Underpin Future Cannabis Breeding

Cannabis (Cannabis sativa L.) has a rich history of human use, and the therapeutic importance of compounds produced by this species is recognized by the medical community. The active constituents of cannabis, collectively called cannabinoids, encompass hundreds of distinct molecules, the most well-characterized of which are tetrahydrocannabinol (THC) and cannabidiol (CBD), which have been used for centuries as recreational drugs and medicinal agents. As a first step to establish a cannabis breeding program, we initiated this study to describe the HPLC-measured quantity of THC and CBD biochemistry profiles of 161 feral pistillate cannabis plants from 20 geographical regions of Iran. Our data showed that Iran can be considered a new region of high potential for distribution of cannabis landraces with diverse THC and CBD content, predominantly falling into three groups, as Type I = THC-predominant, Type II = approximately equal proportions of THC and CBD (both CBD and THC in a ratio close to the unity), and Type III = CBD-predominant. Correlation analysis among two target cannabinoids and environmental and geographical variables indicated that both THC and CBD contents were strongly influenced by several environmental–geographical factors, such that THC and CBD contents were positively correlated with mean, min and max annual temperature and negatively correlated with latitude, elevation, and humidity. Additionally, a negative correlation was observed between THC and CBD concentrations, suggesting that further studies to unravel these genotype × environment interactions (G × E interactions) are warranted. The results of this study provide important pre-breeding information on a collection of cannabis that will underpin future breeding programs.

A Case Study of Post Occupancy Evaluation of an Educational Building with LEED Platinum Rating

The Building environment and the performance of its systems directly impact the experience and comfort of a building occupant. This POE study examines the relationship between building and human performance. LEED-rated building was selected as a case study to analyze its performance after being in operation. The occupants’ satisfaction was evaluated in terms of the thermal comfort and human use with the application of online questionnaire. The environmental impact was determined through various measurements including room temperature, relative humidity, air velocity, lighting levels and carbon emission. The outcomes of this study identify the building systems efficiencies as well as the systems in need of retrofit. The POE results can help building designers address user needs more effectively and fine-tune the systems to improve sustainability.

A Narrative Review of COVID-19 Vaccines

The COVID-19 pandemic has shaken the world since early 2020 and its health, social, economic, and societal negative impacts at the global scale have been catastrophic. Since the early days of the pandemic, development of safe and effective vaccines was judged to be the best possible tool to minimize the effects of this pandemic. Drastic public health measures were put into place to stop the spread of the virus, with the hope that vaccines would be available soon. Thanks to the extraordinary commitments of many organizations and individuals from around the globe and the collaborative effort of many international scientists, vaccines against COVID-19 received regulatory approval for emergency human use in many jurisdictions in less than a year after the identification of the viral sequence. Several of these vaccines have been in use for some time; however, the pandemic is still ongoing and likely to persist for the foreseeable future. This is due to many reasons including reduced compliance with public health restrictions, limited vaccine manufacturing/distribution capacity, high rates of vaccine hesitancy, and the emergence of new variants with the capacity to spread more easily and to evade current vaccines. Here we discuss the discovery and availability of COVID-19 vaccines and evolving issues around mass vaccination programs.