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1.
Viruses ; 15(4)2023 04 11.
Article in English | MEDLINE | ID: covidwho-2295003

ABSTRACT

The Bunyavirales order is a large group of RNA viruses that includes important pathogens for humans, animals and plants. With high-throughput screening of clinically tested compounds we have looked for potential inhibitors of the endonuclease domain of a bunyavirus RNA polymerase. From a list of fifteen top candidates, five compounds were selected and their antiviral properties studied with Bunyamwera virus (BUNV), a prototypic bunyavirus widely used for studies about the biology of this group of viruses and to test antivirals. Four compounds (silibinin A, myricetin, L-phenylalanine and p-aminohippuric acid) showed no antiviral activity in BUNV-infected Vero cells. On the contrary, acetylsalicylic acid (ASA) efficiently inhibited BUNV infection with a half maximal inhibitory concentration (IC50) of 2.02 mM. In cell culture supernatants, ASA reduced viral titer up to three logarithmic units. A significant dose-dependent reduction of the expression levels of Gc and N viral proteins was also measured. Immunofluorescence and confocal microscopy showed that ASA protects the Golgi complex from the characteristic BUNV-induced fragmentation in Vero cells. Electron microscopy showed that ASA inhibits the assembly of Golgi-associated BUNV spherules that are the replication organelles of bunyaviruses. As a consequence, the assembly of new viral particles is also significantly reduced. Considering its availability and low cost, the potential usability of ASA to treat bunyavirus infections deserves further investigation.


Subject(s)
Bunyamwera virus , Orthobunyavirus , Humans , Animals , Chlorocebus aethiops , Bunyamwera virus/genetics , Antiviral Agents/pharmacology , Vero Cells , Aspirin/pharmacology , Cell Culture Techniques
2.
Cardiometry ; 24:360-366, 2022.
Article in English | EMBASE | ID: covidwho-2277741

ABSTRACT

Cardiovascular disease (CVD) is the leading cause of death in most developed countries, including the United States, with a significant economic impact. Lifestyle changes and the administration of antiplatelet medication, like aspirin, may significantly contribute to the secondary prevention of CVD in adults. For years, aspirin has been utilized for both secondary and primary cardiovascular disease prevention. Aspirin has been extensively used because of the belief that it may have a positive impact on primary prevention, despite the debate surrounding its usage. This study briefly examines usage patterns and discusses the potential variables and factors that can decrease the ability of aspirin to prevent cardiovascular disease. The present study also explore the key studies of aspirin use in the context of recent recommendations. The risk of bleeding has been observed to significantly rise, although large randomized clinical studies have demonstrated a reduction or absence of CVD events. Prevention strategies for cardiovascular disease with low-dose aspirin are no longer advised for persons at intermediate risk. To determine whether taking aspirin is worth the potential dangers, the benefits must be evaluated.Copyright © 2022 Novyi Russkii Universitet. All rights reserved.

3.
Int J Mol Sci ; 22(13)2021 Jun 23.
Article in English | MEDLINE | ID: covidwho-1282518

ABSTRACT

The usefulness of anti-inflammatory drugs as an adjunct therapy to improve outcomes in COVID-19 patients is intensely discussed in this paper. Willow bark (Salix cortex) has been used for centuries to relieve pain, inflammation, and fever. Its main active ingredient, salicin, is metabolized in the human body into salicylic acid, the precursor of the commonly used pain drug acetylsalicylic acid (ASA). Here, we report on the in vitro anti-inflammatory efficacy of two methanolic Salix extracts, standardized to phenolic compounds, in comparison to ASA in the context of a SARS-CoV-2 peptide challenge. Using SARS-CoV-2 peptide/IL-1ß- or LPS-activated human PBMCs and an inflammatory intestinal Caco-2/HT29-MTX co-culture, Salix extracts, and ASA concentration-dependently suppressed prostaglandin E2 (PGE2), a principal mediator of inflammation. The inhibition of COX-2 enzyme activity, but not protein expression was observed for ASA and one Salix extract. In activated PBMCs, the suppression of relevant cytokines (i.e., IL-6, IL-1ß, and IL-10) was seen for both Salix extracts. The anti-inflammatory capacity of Salix extracts was still retained after transepithelial passage and liver cell metabolism in an advanced co-culture model system consisting of intestinal Caco-2/HT29-MTX cells and differentiated hepatocyte-like HepaRG cells. Taken together, our in vitro data suggest that Salix extracts might present an additional anti-inflammatory treatment option in the context of SARS-CoV-2 peptides challenge; however, more confirmatory data are needed.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Aspirin/pharmacology , COVID-19 Drug Treatment , COVID-19/immunology , Plant Extracts/pharmacology , Anti-Inflammatory Agents/chemistry , Benzyl Alcohols/metabolism , COVID-19/virology , Caco-2 Cells , Cyclooxygenase 2/drug effects , Cytokines/metabolism , Dinoprostone/metabolism , Glucosides/metabolism , HT29 Cells , Humans , Inflammation , Leukocytes, Mononuclear/drug effects , Lipopolysaccharides/immunology , Plant Bark/chemistry , Plant Extracts/chemistry , SARS-CoV-2/immunology
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