A Review of In Silico Research, SARS-CoV-2, and Neurodegeneration: Focus on Papain-Like Protease.

Since the appearance of SARS-CoV-2 and the COVID-19 pandemic, the search for new approaches to treat this disease took place in the scientific community. The in silico approach has gained importance at this moment, once the methodologies used in this kind of study allow for the identification of specific protein-ligand interactions, which may serve as a filter step for molecules that can act as specific inhibitors. In addition, it is a low-cost and high-speed technology. Molecular docking has been widely used to find potential viral protein inhibitors for structural and non-structural proteins of the SARS-CoV-2, aiming to block the infection and the virus multiplication. The papain-like protease (PLpro) participates in the proteolytic processing of SARS-CoV-2 and composes one of the main targets studied for pharmacological intervention by in silico methodologies. Based on that, we performed a systematic review about PLpro inhibitors from the perspective of in silico research, including possible therapeutic molecules in relation to this viral protein. The neurological problems triggered by COVID-19 were also briefly discussed, especially relative to the similarities of neuroinflammation present in Alzheimer's disease. In this context, we focused on two molecules, curcumin and glycyrrhizinic acid, given their PLpro inhibitory actions and neuroprotective properties and potential therapeutic effects on COVID-19.

Changes in behavioral and neuronal parameters by alcohol, cigarette, or their combined use in rats.

Few studies have explored the effects of the combined use of alcohol and cigarette in humans, despite its prevalence. Here we evaluated the effect of isolated and combined use on behaviors and neuronal parameters in rats. Male adult rats were divided into alcohol (AL, 2 g/kg, by oral gavage), cigarette smoke (TB, six cigarettes, by inhalation), combined use (ALTB), or control (CT, water by oral gavage and environmental air) groups, treated twice a day (09.00 and 14.00 h). After 4 weeks, the rats were tested in the open field for behavioral analysis and euthanized for brain volume estimation and counting of neurons in the hippocampus. All treatments increased locomotion, and this behavior was higher in the ALTB than TB group. Latency to exit from the central area was lower in the ALTB than in the AL or CT groups. Rearing behavior increased in TB and decreased in AL and ALTB rats. Combined ALTB rats significantly increased their grooming behavior. Only the AL group showed decreased neuron counts and increased brain volume. Our results show that the isolated and combined uses of alcohol and cigarette smoke have diverse effects on behavioral and neuronal parameters in rats after long-term treatment.