A synthetic bispecific antibody capable of neutralizing SARS-CoV-2 Delta and Omicron

Bispecific antibodies have emerged as a promising strategy for curtailing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune escape. This brief report highlights RBT-0813 (also known as TB493-04), a synthetic, humanized, receptor-binding domain (RBD)-targeted bispecific antibody that retains picomolar affinity to the Spike (S) trimers of all major variants of concern and neutralizes both SARS-CoV-2 Delta and Omicron in vitro.

An approach to evaluate the ability of rats to discriminate different levels of illumination in the plus maze test: effects of scopolamine.

Previous research has shown that the visual system is important for rats to establish the arm preference in the elevated plus maze (EPM), an animal model of anxiety. This study aims at evaluating whether a gradient of illumination between the enclosed arms of the maze (E/E(DeltaLux)) could be a reliable approach to detect drugs-induced harmful effect on visual discrimination of rats. Four EPM configurations with different E/E(DeltaLux) (8, 41 and 85lx) were used to demonstrate that as E/E(DeltaLux) increases, rats avoid to explore the light enclosed arm, which characterizes the animal ability to discriminate the most illuminated area within the protected environment of the maze. The establishment of either 41 or 85 E/E(DeltaLux) failed to alter the traditional spatial-temporal variables in the EPM. In addition, systemic treatment with midazolam (MDZ; 1.0mgkg(-1), a classical anxiolytic) induced anxiolysis in rats tested in 41 and 85 E/E(DeltaLux) EPM, with no change in the visual discrimination, when evaluated by the level of light enclosed arm exploration. Systemic treatment with scopolamine (SCP; 1.0, 2.0 and 8.0mgkg(-1)), a drug endowed with harmful properties upon the visual system, did not change either the open arm avoidance or the visual discrimination at the low doses, but induced increased light enclosed arm (visual discrimination deficit) and open arm exploration (anxiolytic like effect) at a higher dose. We propose that the incorporation of an E/E(DeltaLux) in the EPM may reinforce the predict validity of the test since it enables to evaluate whether a visual discrimination deficit can be confounded with an anxiolytic-like effect, thus establishing a false positive detection.

The effects of metabolic stress and vagotomy on emotional learning in an animal model of anxiety.

The aim of the present study is to evaluate the role of the blood glucose (BG) level in emotional learning in the elevated plus maze (EPM), an animal model of anxiety. In Experiment 1, male Wistar rats were submitted to different EPM trial lengths (1- or 5-min). Blood samples were withdrawn before and after the maze exploration, through a polyethylene cannula chronically implanted into the jugular vein. In Experiment 2, the animals received either saline or 2-deoxy-D-glucose, a glucoprivic drug (2-DG, 250 or 500 mg kg(-1)) by i.p. route, 30 min before a 5-min EPM exposure and were retested in the maze (Trial1/Trial2 EPM procedure) 24 h later. In an independent group of rats, blood samples were withdrawn 0, 5, 15, and 30 min after 2-DG administration, through the jugular vein, to determine BG. In Experiment 3, the animals underwent a vagotomy and were tested in a Trial1/Trial2 EPM procedure four weeks later. The results showed that rats exploring the EPM for 5 min displayed increased fear and higher hyperglycemia than those exploring the EPM for 1 min. In addition, rats submitted to 5-min EPM Trial1 length displayed higher level of fear on Trial2, as well as higher percentage of shortening of the %Open arm entries and %Open arm time from Trial1 to Trial2, which characterizes the occurrence of emotional learning. In contrast, rats previously vagotomized or treated with 2-DG (500 mg kg(-1)) showed the same level of fear on both EPM trials and a low percentage of shortening, from Trial1 to Trial2, of the %Open arm entries and %Open arm time, indicating poor emotional learning. The data is discussed regarding the role of glycaemia in emotional learning in the EPM.