SARS-CoV-2 PLpro Inhibition: Evaluating in Silico Repurposed Fidaxomicin's Antiviral Activity Through In Vitro Assessment

The emergence of drug-resistant viruses and novel strains necessitates the rapid development of novel antiviral therapies. This need was particularly demanding during the COVID-19 pandemic. While de novo drug development is a time-consuming process, repurposing existing approved medications offers a more expedient approach. In our prior in silico screening of the DrugBank database, fidaxomicin emerged as a potential SARS-CoV-2 papain-like protease inhibitor. This study extends those findings by investigating fidaxomicin‘s antiviral properties in vitro. Our results support further exploration of fidaxomicin as a therapeutic candidate against SARS-CoV-2, given its promising in vitro antiviral activity and favorable safety profile

In Silico and In Vitro Inhibition of SARS-CoV-2 PLpro with Gramicidin D

Finding an effective drug to prevent or treat COVID-19 is of utmost importance in tcurrent pandemic. Since developing a new treatment takes a significant amount of time, drug repurposing can be an effective option for achieving a rapid response. This study used a combined in silico virtual screening protocol for candidate SARS-CoV-2 PLpro inhibitors. The Drugbank database was searched first, using the Informational Spectrum Method for Small Molecules, followed by molecular docking. Gramicidin D was selected as a peptide drug, showing the best in silico interaction profile with PLpro. After the expression and purification of PLpro, gramicidin D was screened for protease inhibition in vitro and was found to be active against PLpro. The current study’s findings are significant because it is critical to identify COVID-19 therapies that are efficient, affordable, and have a favorable safety profil

In Silico and In Vitro Inhibition of SARS-CoV-2 PLpro with Gramicidin D

Finding an effective drug to prevent or treat COVID-19 is of utmost importance in tcurrentpandemic. Since developing a new treatment takes a significant amount of time, drug repurposingcan be an effective option for achieving a rapid response. This study used a combined in silico virtualscreening protocol for candidate SARS-CoV-2 PLpro inhibitors. The Drugbank database was searchedfirst, using the Informational Spectrum Method for Small Molecules, followed by molecular docking.Gramicidin D was selected as a peptide drug, showing the best in silico interaction profile with PLpro.After the expression and purification of PLpro, gramicidin D was screened for protease inhibitionin vitro and was found to be active against PLpro. The current study’s findings are significantbecause it is critical to identify COVID-19 therapies that are efficient, affordable, and have a favorablesafety profile.This article belongs to the Special Issue Molecular Interactions and Mechanisms of COVID-19 Inhibition 2.

In Silico and In Vitro Inhibition of SARS-CoV-2 PLpro with Gramicidin D

Finding an effective drug to prevent or treat COVID-19 is of utmost importance in tcurrent pandemic. Since developing a new treatment takes a significant amount of time, drug repurposing can be an effective option for achieving a rapid response. This study used a combined in silico virtual screening protocol for candidate SARS-CoV-2 PLpro inhibitors. The Drugbank database was searched first, using the Informational Spectrum Method for Small Molecules, followed by molecular docking. Gramicidin D was selected as a peptide drug, showing the best in silico interaction profile with PLpro. After the expression and purification of PLpro, gramicidin D was screened for protease inhibition in vitro and was found to be active against PLpro. The current study’s findings are significant because it is critical to identify COVID-19 therapies that are efficient, affordable, and have a favorable safety profile

Theories of Change and Mediators of Psychotherapy Effectiveness in Adolescents With Externalising Behaviours: A Systematic Review

bstract Background Externalising behaviours are becoming a remarkably prevalent problem during adolescence, often precipitating both externalising and internalising disorders in later adulthood. Psychological treatments aim to increase the social functioning of adolescents in order for them to live a more balanced life and prevent these negative trajectories. However, little is known of the intervening variables and mediators involved in these treatments' change mechanisms. We conducted a systematic review, exploring the available evidence on mediators of psychological treatments for externalising behaviours and symptoms amongst adolescents (10 to 19 years old). Methods A systematic search was performed on Medline and PsycINFO databases, which identified studies from inception to February 23, 2020. Eligible studies included randomised controlled trials that enrolled adolescents with externalising symptoms and behaviours as, at least, one of the primary outcomes. A group of 20 reviewers from the COST-Action TREATme (CA16102) were divided into 10 pairs. Each pair independently screened studies for inclusion, extracted information from the included studies, and assessed the methodological quality of the included studies and the requirements for mediators, following Kazdin's criteria. Risk of bias of RCTs was assessed by the Mixed Methods Appraisal Tool. Extracted data from the included studies were reported using a narrative synthesis. Results Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), after removing duplicates, 3,660 articles were screened. Disagreements were resolved by consensus. In a second stage, 965 full-text articles were assessed for eligibility. A total of 14 studies fulfilled all inclusion criteria. The majority were related to systemic psychological treatment approaches. Two types of mediators were identified as potentially being involved in the mechanisms of change for better social improvements of adolescents: to increase healthier parent–adolescent relationships and parental discipline. However, there were significant and non-significant results amongst the same mediators, which led to discussing the results tentatively. Conclusions Family variables were found to be the largest group of investigated mediators, followed by relational, behavioural, and emotional variables. No cognitive or treatment-specific mediators were identified. Both adequate behavioural control of adolescents' peer behaviour and a better positive balance in their relationships with their parents seemed to buffer the effects of externalising behaviours in adolescents. Several methodological limitations concerning mediation testing design, outcome measures, and mediator selection have been identified. Ethics and Dissemination Ethical approval was not required. PROSPERO registration number: CRD42021231835

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts. June 4-7, 2019, Szczyrk, Polan

Kloniranje proteaze slične papainu PL pro SARS-CoV-2 u E.coli, heterologna ekspresija, prečišćavanje i razvoj inhibitornog enzimskog eseja za pretragu potencijalnih lekova

Pandemija izazvana virusom SARS-CoV-2 se pojavila krajem decembra 2019. godine u Vuhanu u Kini, kada su prvi put zapažena teška respiratorna oboljenja. Od tada se virus brzo proširio u Kini, ali i u drugim državama i izazvao veliku globalnu zabrinutost. U Srbiji je polovinom marta 2020. nakon registrovanja prvih slučajeva obolelih i proglašenja pandemije od strane Svetske zdravstvene organizacije uvedeno vanredno stanje. Novi virus SARS-CoV-2 je dobio ime zbog svoje strukturne sličnosti sa korona virusima koji izazivaju teške respiratorne simptome