The potential of remdesivir to affect function, metabolism and proliferation of cardiac and kidney cells in vitro

Merches, Katja; Breunig, Leonie; Fender, Julia; Brand, Theresa; Bätz, Vanessa; Idel, Svenja; Kollipara, Laxmikanth; Reinders, Yvonne; Sickmann, Albert; Mally, Angela; Lorenz, Kristina

doi:10.1007/s00204-022-03306-1

Cited by 14 publications

(12 citation statements)

References 102 publications

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“…Further, the toxicity of the chemotherapeutic agent SU was studied in vitro using the cardiomyoblast cell line H9c2 as a model system for cardiomyocyte toxicity ( Merches et al, 2022 ). WB of cleaved caspase-3 (p19/p17 caspase-3) and caspase-3 revealed slight changes after a 24 h treatment of SU loaded in pSiNPs or SU alone ( Figure 6C ); the effects were more pronounced when the cells were treated with higher concentration of SU-pSiNPs (50 μM), similar to that seen in HCT 116 cells.…”

Section: Resultsmentioning

confidence: 99%

“…The presence of characteristic Raman modes of SU ( Litti et al, 2016 ) and pSiNPs ( Tolstik et al, 2016b ) can facilitate its label-free tracking by applying Raman spectroscopy. For in vitro studies, to evaluate the cardiotoxicity of SU-loaded pSiNPs, the following two cell lines were chosen: the human colon carcinoma HCT 116 cell line ( Rajput et al, 2008 ) that is applied widely as a model to study the cellular effects of SU ( Sun et al, 2012 ; Ban et al, 2017 ; Elgendy et al, 2017 ) and the rat cardiomyoblast cell line H9c2 ( Korashy et al, 2015 ; Tomasovic et al, 2020 ; Merches et al, 2022 ). Thereby, the intracellular delivery, localization, and toxicity of pure SU substance and SU-loaded pSiNPs were analyzed in vitro using cell viability assays and linear optical imaging techniques.…”

Section: Introductionmentioning

confidence: 99%

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Raman and fluorescence micro-spectroscopy applied for the monitoring of sunitinib-loaded porous silicon nanocontainers in cardiac cells

et al. 2022

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Nanomaterials are a central pillar in modern medicine. They are thought to optimize drug delivery, enhance therapeutic efficacy, and reduce side-effects. To foster this technology, analytical methods are needed to validate not only the localization and distribution of these nanomaterials, but also their compatibility with cells, drugs, and drug release. In the present work, we assessed nanoparticles based on porous silicon (pSiNPs) loaded with the clinically used tyrosine kinase inhibitor sunitinib for their effectiveness of drug delivery, release, and toxicity in colon cancer cells (HCT 116 cells) and cardiac myoblast cells (H9c2) using Raman micro-spectroscopy, high-resolution fluorescence microscopy, along with biological methods for toxicological effects. We produced pSiNPs with a size of about 100 nm by grinding mesoporous silicon layers. pSiNPs allowed an effective loading of sunitinib due to their high porosity. Photoluminescence properties of the nanoparticles within the visible spectrum allowed the visualization of their uptake in cardiac cells. Raman micro-spectroscopy allowed not only the detection of the uptake and distribution of pSiNPs within the cells via a characteristic silicon Raman band at about 518–520 cm−1, but also the localization of the drug based on its characteristic molecular fingerprints. Cytotoxicity studies by Western blot analyses of apoptotic marker proteins such as caspase-3, and the detection of apoptosis by subG1-positive cell fractions in HCT 116 and MTT analyses in H9c2 cells, suggest a sustained release of sunitinib from pSiNPs and delayed cytotoxicity of sunitinib in HCT 116 cells. The analyses in cardiac cells revealed that pSiNPs are well tolerated and that they may even protect from toxic effects in these cells to some extent. Analyses of the integrity of mitochondrial networks as an early indicator for apoptotic cellular effects seem to validate these observations. Our study suggests pSiNPs-based nanocontainers for efficient and safe drug delivery and Raman micro-spectroscopy as a reliable method for their detection and monitoring. Thus, the herein presented nanocontainers and analytical methods have the potential to allow an efficient advancement of nanoparticles for targeted and sustained intracellular drug release that is of need, e.g., in chronic diseases and for the prevention of cardiac toxicity.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Raman and fluorescence micro-spectroscopy applied for the monitoring of sunitinib-loaded porous silicon nanocontainers in cardiac cells

et al. 2022

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“…Remdesivir, the first intravenously administered drug targeting RdRp for SARS-CoV-2 treatment, has yielded contradictory clinical results (26). Concerns over renal toxicity, liver injury, and cardiac safety challenge the safety of remdesivir (72)(73)(74)(75). Molnupiravir, developed by Merck and Ridgeback Biotherapeutics, is the first approved oral anti-SARS-CoV-2 therapy, which also targets RdRp (15).…”

Section: Inhibitors Of Sars-cov-2 Rnadependent Rna Polymerasementioning

confidence: 99%

Oral GS-441524 derivatives: Next-generation inhibitors of SARS‐CoV‐2 RNA‐dependent RNA polymerase

Wang

Yang

Song³

2022

Front. Immunol.

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GS-441524, an RNA‐dependent RNA polymerase (RdRp) inhibitor, is a 1′-CN-substituted adenine C-nucleoside analog with broad-spectrum antiviral activity. However, the low oral bioavailability of GS‐441524 poses a challenge to its anti-SARS-CoV-2 efficacy. Remdesivir, the intravenously administered version (version 1.0) of GS-441524, is the first FDA-approved agent for SARS-CoV-2 treatment. However, clinical trials have presented conflicting evidence on the value of remdesivir in COVID-19. Therefore, oral GS-441524 derivatives (VV116, ATV006, and GS-621763; version 2.0, targeting highly conserved viral RdRp) could be considered as game-changers in treating COVID-19 because oral administration has the potential to maximize clinical benefits, including decreased duration of COVID-19 and reduced post-acute sequelae of SARS-CoV-2 infection, as well as limited side effects such as hepatic accumulation. This review summarizes the current research related to the oral derivatives of GS-441524, and provides important insights into the potential factors underlying the controversial observations regarding the clinical efficacy of remdesivir; overall, it offers an effective launching pad for developing an oral version of GS-441524.

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“…However, this drug is mainly used for hospitalized severe COVID-19 infected patients. Remdesivir is widely used in the COVID-19 treatment all over the world [38,39] .…”

Section: Remdesivir (Veklury)mentioning

confidence: 99%

“…Chemically Remdesivir is a protide (prodrug of nucleotide) broad-spectrum antiviral therapeutic which can diffuse into the cells. The drug mainly interferes with the action of RNA-dependent RNA polymerase and inhibits the RNA polymerase activity [38,39] .…”

Section: Chemistry and Pharmacologymentioning

confidence: 99%

Anti-SARS-CoV-2 Biotherapeutics and Chemotherapeutics: An Insight into Product Specifications and Marketing Dynamics

Kotra¹,

Mallem²,

Kanuri³

et al. 2022

Prog Micobes Mol Biol

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Chemotherapeutics and biotherapeutics agents have been explored as a potential treatment for COVID-19. This study was aimed to elucidate latest update related to biotherapeutics and chemotherapeutics against COVID-19 and its variants as well as the product specifications and marketing dynamics of its pharmacotherapies. There are several chemotherapeutics that have been studied for the treatment of COVID-19, including Paxlovid (Nirmatrelvir & Ritonavir) fixed dose combination, nirmatrelvir and ritonavir fixed dose combination, Remdesivir (Vekulary/Covifor) fixed dose combination, chloroquine and hydroxychloroquine, molnupiravir, favipiravir, Infliximab (Remsima®) fixed dose combination tocilizumab (Actimera), casirivimab+imdevimab (Ronapreve) fixed dose combination, ivermectin, methylprednisole. These drugs have been repurposed for use in COVID-19 due to their antiviral properties and ability to reduce inflammation. The COVID-19 death cases have significantly reduced because of tested efficacy of advanced biotherapeutics and chemotherapeutics. As for marketing dynamics, the demand for chemotherapeutics for the treatment of COVID-19 has increased significantly since the outbreak of the pandemic. Hence, the prices of anti-viral and monoclonal antibodies in top COVID-19 affected countries is also presented here. Considering the molecular interactions, therapeutic activity, efficacy, and adverse effects, the USFDA and the WHO recommended the aforementioned drugs. The chances of approval seems favouring biotherapeutics as these have the best characteristics among the chemotherapeutics. Overall, this review contributes to the scientific understanding of the COVID-19. This can help to inform future research and development efforts and contribute to the overall advancement of knowledge in the field of medicine.

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The potential of remdesivir to affect function, metabolism and proliferation of cardiac and kidney cells in vitro

Cited by 14 publications

References 102 publications

Raman and fluorescence micro-spectroscopy applied for the monitoring of sunitinib-loaded porous silicon nanocontainers in cardiac cells

Raman and fluorescence micro-spectroscopy applied for the monitoring of sunitinib-loaded porous silicon nanocontainers in cardiac cells

Oral GS-441524 derivatives: Next-generation inhibitors of SARS‐CoV‐2 RNA‐dependent RNA polymerase

Anti-SARS-CoV-2 Biotherapeutics and Chemotherapeutics: An Insight into Product Specifications and Marketing Dynamics

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