Unlike Chloroquine, Mefloquine Inhibits SARS-CoV-2 Infection in Physiologically Relevant Cells.

Despite the development of specific therapies against severe acute respiratory coronavirus 2 (SARS-CoV-2), the continuous investigation of the mechanism of action of clinically approved drugs could provide new information on the druggable steps of virus-host interaction. For example, chloroquine (CQ)/hydroxychloroquine (HCQ) lacks in vitro activity against SARS-CoV-2 in TMPRSS2-expressing cells, such as human pneumocyte cell line Calu-3, and likewise, failed to show clinical benefit in the Solidarity and Recovery clinical trials. Another antimalarial drug, mefloquine, which is not a 4-aminoquinoline like CQ/HCQ, has emerged as a potential anti-SARS-CoV-2 antiviral in vitro and has also been previously repurposed for respiratory diseases. Here, we investigated the anti-SARS-CoV-2 mechanism of action of mefloquine in cells relevant for the physiopathology of COVID-19, such as Calu-3 cells (that recapitulate type II pneumocytes) and monocytes. Molecular pathways modulated by mefloquine were assessed by differential expression analysis, and confirmed by biological assays. A PBPK model was developed to assess mefloquine's optimal doses for achieving therapeutic concentrations. Mefloquine inhibited SARS-CoV-2 replication in Calu-3, with an EC50 of 1.2 µM and EC90 of 5.3 µM. It reduced SARS-CoV-2 RNA levels in monocytes and prevented virus-induced enhancement of IL-6 and TNF-α. Mefloquine reduced SARS-CoV-2 entry and synergized with Remdesivir. Mefloquine's pharmacological parameters are consistent with its plasma exposure in humans and its tissue-to-plasma predicted coefficient points suggesting that mefloquine may accumulate in the lungs. Altogether, our data indicate that mefloquine's chemical structure could represent an orally available host-acting agent to inhibit virus entry.

Potential application of oil-suspended particulate matter aggregates (OSA) on the remediation of reflective beaches impacted by petroleum: a mesocosm simulation.

This paper presents the oil-suspended particulate matter aggregate (OSA) resulted from the interaction of droplets of dispersed oil in a water column and particulate matter. This structure reduces the adhesion of oil on solid surfaces, promotes dispersion, and may accelerate degradation processes. The effects of the addition of fine sediments (clay + silt) on the formation of OSA, their impact on the dispersion and degradation of the oil, and their potential use in recovering reflective sandy beaches were evaluated in a mesoscale simulation model. Two simulations were performed (21 days), in the absence and presence of fine sediments, with four units in each simulation using oil from the Recôncavo Basin. The results showed that the use of fine sediment increased the dispersion of the oil in the water column up to four times in relation to the sandy sediment. There was no evidence of the transport of hydrocarbons in bottom sediments associated with fine sediments that would have accelerated the dispersion and degradation rates of the oil. Most of the OSA that formed in this process remained in the water column, where the degradation processes were more effective. Over the 21 days of simulation, we observed a 40 % reduction on average of the levels of saturated hydrocarbons staining the surface oil.

Spatial distribution and concentration assessment of total petroleum hydrocarbons in the intertidal zone surface sediment of Todos os Santos Bay, Brazil.

The primary objective of this study was to investigate the concentrations and spatial distribution of the total petroleum hydrocarbons (TPHs) in the intertidal zone surface sediment of Todos os Santos Bay, Brazil, to assess the distribution and degree of contamination by TPHs, measure the level of TPH degradation in the surface sediment, and identify the organic matter sources. The surface sediment used in this study was collected in 50 stations, and TPHs, isoprenoid alkanes (pristane and phytane), and unresolved complex mixture (UCM) were analyzed by gas chromatography with a flame ionization detector. The total concentrations ranged from 0.22 to 40,101 µg g(-1) dry weight and showed a strong correlation with the total organic carbon (TOC) content. The highest TPH concentrations were observed in samples from the mangrove sediments of a river located near a petroleum refinery. Compared with other studies in the world, the TPH concentrations in the intertidal surface sediment of Todos os Santos Bay were below average in certain stations and above average in others. An analysis of the magnitude of UCM (0.11 to 17,323 µg g(-1) dry weight) and the ratios nC17/Pr and nC18/Ph suggest that an advanced state of oil weathering, which indicates previous contamination. The molar C/N ratios varied between 5 and 43, which indicate organic matter with a mixed origin comprising marine and continental contributions.