Психиатрия и психофармакотерапия., Год журнала: 2024, Номер 26(2)
Опубликована: Апрель 1, 2024
В ФОКУСЕ Применение психотропных препаратов в соматической медицине (Обзор литературы) Р.А.Беккер
Язык: Русский
medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Янв. 18, 2024
Abstract Background The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine were repurposed for the treatment of early COVID-19 based on their antiviral activity in vitro , observational clinical trial evidence suggesting they prevented progression to severe disease. However, these SSRIs have not been recommended guidelines vivo has characterised. Methods PLATCOV is an open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform running Thailand, Brazil, Pakistan, Laos. We recruited low-risk adult outpatients aged 18-50 with symptomatic (symptoms <4 days). Patients assigned using block randomisation one eleven arms including oral (40mg/day 7 days), or no study drug. Uniform ratios applied across active groups while drug group comprised ≥20% patients at all times. primary endpoint was rate oropharyngeal viral clearance assessed a modified intention-to-treat population (>2 days follow-up). estimated under Bayesian hierarchical linear model fitted log10 densities standardised duplicate swab eluates taken daily over week (18 measurements per patient). This ongoing registered ClinicalTrials.gov ( NCT05041907 ). Findings Between 5 April 2022 8 May 2023 271 concurrently randomised either (n=120) (n=151). Fluoxetine well tolerated accelerated relative arm by 15% (95% credible interval (CrI): 2% 34%). In pooled meta-analysis unblinded substantially less than ritonavir-boosted nirmatrelvir-85% increase CrI: 61 112%); remdesivir 35% (14 59%), molnupiravir 37% 60%), casirivimab/imdevimab 29% (10 48%). Interpretation against SARS-CoV-2. Although level efficacy other currently available drugs, might still be useful prophylaxis where effect required. Funding Wellcome Trust Grant ref: 223195/Z/21/Z through Therapeutics Accelerator. Evidence before this proposed as therapeutics initially observational, evidence. reports suggested that taking had reduced probability developing dying. searched PubMed EMBASE studies English up until 30 th November search terms “fluoxetine”, “fluvoxamine” “COVID-19” restricted controlled trials (RCTs). Eight outpatient RCTs identified. There outpatients. A compatible moderate reduction hospitalisation death risk ratio 0.80 CI: 0.62,1.01). Added value showed illness SSRI weak . antivirals such nirmatrelvir molnupiravir. approach described here provides quantitative measure effects tractable sample sizes. Implications COVID-19. insufficient but, required prevent infection, could beneficial prophylaxis.
Язык: Английский
Процитировано
4
EClinicalMedicine, Год журнала: 2025, Номер 80, С. 103036 - 103036
Опубликована: Янв. 18, 2025
Язык: Английский
Процитировано
0
Current Issues in Molecular Biology, Год журнала: 2023, Номер 45(10), С. 7956 - 7973
Опубликована: Сен. 28, 2023
Ceramides and other related sphingolipids, important cellular components linked to metabolic homeostasis cardiometabolic diseases, have been found be involved in different steps of the SARS-CoV-2 life cycle. Hence, changes their physiological levels are identified as predictors COVID-19 severity prognosis, well potential therapeutic targets. In this review, an overview cycle is given, followed by a description sphingolipid metabolism its role viral infection, with particular focus on those required finalize Furthermore, use development pharmaceutical strategies target sphingolipids prevent treat severe long-term symptoms infectious particularly COVID-19, reviewed herein. Finally, research perspectives current challenges field highlighted. Although many aspects not fully known, review aims highlight how discovery molecules targeting reliable selective properties may offer new alternatives including COVID-19.
Язык: Английский
Процитировано
6
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Ноя. 5, 2024
Abstract M is the most abundant structural membrane protein in coronaviruses and essential for formation of infectious virus particles. SARS-CoV-2 adopts two conformations, short long , regulated transition between states hypothesized to coordinate viral assembly budding. However, factors that regulate conformation roles each state are unknown. Here, we discover a direct M-sphingolipid interaction controls conformational dynamics assembly. We show binds Golgi-enriched anionic lipids including ceramide-1-phosphate (C1P). Molecular simulations C1P promotes energetically stabilizes . Cryo-EM structures specifically at conserved site bridging transmembrane cytoplasmic regions. Disrupting -C1P alters subcellular localization, reduces with Spike E, impairs subsequent virus-like particle cell entry. Together, these results endogenous signaling structure support model which stabilized early endomembrane system organize other proteins prior
Язык: Английский
Процитировано
2
Психиатрия и психофармакотерапия., Год журнала: 2024, Номер 26(2)
Опубликована: Апрель 1, 2024
В ФОКУСЕ Применение психотропных препаратов в соматической медицине (Обзор литературы) Р.А.Беккер
Язык: Русский
Процитировано
0