A Promising Strategy Against SARS-CoV-2 Infected Patients: Antisense Therapy

Çubuk, Hasan

doi:10.26434/chemrxiv.12948746.v1

Cited by 3 publications

(1 citation statement)

References 15 publications

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“…(13) Secondly, because of the hydrophobicity of nucleobases and the backbone flexibility, mRNA can fold into different 3D motifs which can interfere with the mRNA-ASO hybridization and the selectivity. (12) Thus, one either tries to target more unstructured regions of mRNA (14) or screen large libraries of different ASOs. (2,12) Recent studies have highlighted the importance of taking the 3D structure of RNA targets into account in the design of ASOs.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic Insights into ASO-RNA Complexation: Advancing Antisense Oligonucleotide Design Strategies

Hörberg,

Carlesso,

Reymer

2024

Preprint

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Oligonucleotide drugs, an emerging modulator class, hold promise for targeting previously undruggable biomacromolecules. To date, only 18 oligonucleotide drugs, including sought-after antisense oligonucleotides (ASO) and splice-switching oligonucleotides (SSO), have FDA approval. These agents effectively bind mRNA, inducing degradation or modulating splicing. Current oligonucleotide drug design strategies prioritize full Watson-Crick base pair complementarity, overlooking mRNA target 3D shapes. Given that mRNA conformational diversity can impact hybridization, incorporating mRNA key-structural properties into the design may expedite ASO lead discovery. Using atomistic molecular dynamics simulations inspired by experimental data, we demonstrate the advantages of incorporating common triple base pairs into the design of antisense oligonucleotides (ASOs) targeting RNA hairpin motifs, which are highly accessible regions for interactions. By employing an RNA pseudoknot modified into an ASO-hairpin complex, we investigate the effects of ASO length and hairpin loop mutations. Our findings suggest that ASO-mRNA complex stability is influenced by ASO length, number of common triple base pairs, and the dynamic accessibility of bases in the hairpin loop. Our study offers new mechanistic insights into ASO-mRNA complexation and underscores the value of pseudoknots in constructing training datasets for machine learning models aimed at designing novel ASO leads.

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Section: Introductionmentioning

confidence: 99%

Mechanistic Insights into ASO-RNA Complexation: Advancing Antisense Oligonucleotide Design Strategies

Hörberg,

Carlesso,

Reymer

2024

Preprint

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COCARDE Study–Cardiac Imaging Phenotype in Patients With COVID-19: Protocol for a Prospective Observational Study

Lairez¹,

Blanchard²,

Balardy³

et al. 2022

JMIR Res Protoc

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Background The effects of SARS-CoV-2 (COVID-19) on the myocardium and their role in the clinical course of infected patients are still unknown. The severity of SARS-CoV-2 is driven by hyperinflammation, and the effects of SARS-CoV-2 on the myocardium may be significant. This study proposes to use bedside observations and biomarkers to characterize the association of COVID-19 with myocardial injury. Objective The aim of the study is to describe the myocardial function and its evolution over time in patients infected with SARS-CoV-2 and to investigate the link between inflammation and cardiac injury. Methods This prospective, monocentric, observational study enrolled 150 patients with suspected or confirmed SARS-CoV-2 infection at Toulouse University Hospital, Toulouse, France. Patients admitted to the intensive care unit (ICU), regular cardiologic ward, and geriatric ward of our tertiary university hospital were included during the pandemic period. Blood sampling, electrocardiography, echocardiography, and morphometric and demographic data were prospectively collected. Results A total of 100 patients were included. The final enrolment day was March 31, 2020, with first report of results at the end of the first quarter of 2021. The first echocardiographic results at admission of 31 patients of the COCARDE-ICU substudy population show that biological myocardial injury in COVID-19 has low functional impact on left ventricular systolic function. Conclusions A better understanding of the effects of COVID-19 on myocardial function and its link with inflammation would improve patient follow-up and care. Trial Registration Clinicaltrials.gov NCT04358952; https://clinicaltrials.gov/ct2/show/NCT04358952 International Registered Report Identifier (IRRID) DERR1-10.2196/24931

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COCARDE Study–Cardiac Imaging Phenotype in Patients With COVID-19: Protocol for a Prospective Observational Study (Preprint)

Lairez¹,

Blanchard²,

Balardy³

et al. 2020

Preprint

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UNSTRUCTURED Background – The effects of SARS-Cov-2 (COVID-19) on the myocardium and their role in the clinical course of infected patients are still unknown. The severity of SARS-Cov-2 is driven by hyperinflammation and the effects of SARS-Cov-2 on the myocardium may be significant. The present study proposes to use bedside observations and biomarkers to characterize the association COVID-19 with myocardial injury. Objectives – The aim of the study is to describe the myocardial function and its evolution over the time in patients infected with SARS-COV-2; and to investigate the link between inflammation and cardiac injury. Design – This prospective, monocentric observational study will enroll 150 patients with suspected or confirmed SARS-COV-2 infection at Toulouse University Hospital, Toulouse, France. Patients admitted in intensive care unit, regular cardiologic ward as well as geriatric ward of our tertiary university hospital will be included during the pandemic period. Blood sampling, electrocardiography, echocardiography, as well as morphometric and demographic data will be prospectively collected. Implications – A better understanding of the effects of COVID-19 on myocardia function and the links with inflammation would improve patient follow-up and care. Trial registration – Clinicaltrials.gov NCT04358952

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A Promising Strategy Against SARS-CoV-2 Infected Patients: Antisense Therapy

Cited by 3 publications

References 15 publications

Mechanistic Insights into ASO-RNA Complexation: Advancing Antisense Oligonucleotide Design Strategies

Mechanistic Insights into ASO-RNA Complexation: Advancing Antisense Oligonucleotide Design Strategies

COCARDE Study–Cardiac Imaging Phenotype in Patients With COVID-19: Protocol for a Prospective Observational Study

COCARDE Study–Cardiac Imaging Phenotype in Patients With COVID-19: Protocol for a Prospective Observational Study (Preprint)

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