The heat shock protein 90 inhibitor RGRN-305 attenuates SARS-CoV-2 spike protein-induced inflammation in vitro but lacks effectiveness as COVID-19 treatment in mice DOI Creative Commons
Hakim Ben Abdallah,

Giorgia Marino,

Manja Idorn

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(9), P. e0310915 - e0310915

Published: Sept. 26, 2024

The inhibition of heat shock protein 90 (HSP90), a molecular chaperone, has been proposed to be potential novel treatment strategy for Coronavirus disease 2019 (COVID-19). In contrast other studies, our data demonstrated that RGRN-305, HSP90 inhibitor, exacerbated the cytopathic effect and did not reduce viral shedding in VeroE6-hTMPRSS2 cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Likewise murine model SARS-CoV-2, transgenic mice treated orally RGRN-305 exhibited reduced survival by end experiment (day 12) as 14% (1/7) survived compared 63% (5/8) those drug-vehicle. Animal weight was treatment. Interestingly, we significantly dampened inflammatory response induced SARS-CoV-2 spike human macrophage-like (U937) lung epithelial (A549). Measured quantitative real-time PCR, mRNA expression proinflammatory cytokines TNF , IL1B IL6 were reduced. Together, these suggest exacerbates infection vitro reduces but exhibits strong anti-inflammatory properties. This shows while may helpful ‘cytokine storm’, it no beneficial impact on replication or animals monotherapy. Further animal studies inhibitors combination an anti-viral drug provide additional insights into its utility infections whether continue COVID-19 disease.

Language: Английский

Human coronaviruses activate and hijack the host transcription factor HSF1 to enhance viral replication DOI Creative Commons
Silvia Pauciullo, Anna Riccio, Silvia Santopolo

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Sept. 7, 2024

Language: Английский

Citations

3
Protective role of the HSP90 inhibitor, STA-9090, in lungs of SARS-CoV-2-infected Syrian golden hamsters DOI Creative Commons
Luiz Gustavo Teixeira Alves, Morris Baumgardt, Christine Langner

et al.

BMJ Open Respiratory Research, Journal Year: 2024, Volume and Issue: 11(1), P. e001762 - e001762

Published: Feb. 1, 2024

Introduction The emergence of new SARS-CoV-2 variants, capable escaping the humoral immunity acquired by available vaccines, together with waning and vaccine hesitancy, challenges efficacy vaccination strategy in fighting COVID-19. Improved therapeutic strategies are urgently needed to better intervene particularly severe cases disease. They should aim at controlling hyperinflammatory state generated on infection, reducing lung tissue pathology inhibiting viral replication. Previous research has pointed a possible role for chaperone HSP90 replication COVID-19 pathogenesis. Pharmacological intervention through inhibitors was shown be beneficial treatment inflammatory diseases, infections diverse viruses. Methods In this study, we investigated effects potent inhibitor Ganetespib (STA-9090) vitro alveolar epithelial cells macrophages characterise its cell activation Additionally, Syrian hamster animal model used evaluate systemic inflammation burden after infection. Results vitro, STA-9090 reduced dose-dependent manner lowered significantly expression proinflammatory genes, both macrophages. vivo, although no reduction load observed, administration led an overall improvement clinical condition infected animals, oedema formation pathology. Conclusion Altogether, show that inhibition could serve as potential option moderate

Language: Английский

Citations

2
Deciphering the potential therapeutic targets and mechanisms of jaranol for the treatment of COVID-19 and lung adenocarcinoma DOI Creative Commons

Zhongcui Kang,

Qian Wu,

Qihang Peng

et al.

Arabian Journal of Chemistry, Journal Year: 2024, Volume and Issue: 17(3), P. 105648 - 105648

Published: Jan. 24, 2024

Patients with lung adenocarcinoma (LUAD) are vulnerable to COVID-19. However, there is currently a lack of available treatments for LUAD patients infected Jaranol naturally derived flavonoid that exhibits promising properties as an antiviral and antitumor agent. Therefore, this research intends investigate the molecular targets underlying mechanisms jaranol treatment COVID-19/LUAD. Through network pharmacology, 47 intersection target genes were identified against COVID-19/LUAD, eight-gene risk score model strong predictive accuracy was constructed. Functional enrichment analysis demonstrated main mechanism in combating COVID-19/LUAD involved regulation response hormone, positive phosphorylation, PI3K-Akt signaling pathway. Furthermore, results docking indicated exhibited significant affinity eight hub (AKT1, SRC, EGFR, HSP90AA1, ESR1, PTGS2, PPARG, MMP9) well three core COVID-19-related (ACE2, 3CLpro, PLpro). The direct binding between MMP9 then validated A549 cancer cells using cellular thermal shift assay (CETSA). These findings suggest has therapeutic effect providing theoretical foundation novel perspectives future development potential pharmaceutical candidate.

Language: Английский

Citations

1
1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit DOI Open Access
Jozef Nahálka

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4440 - 4440

Published: April 18, 2024

The COVID-19 pandemic prompted rapid research on SARS-CoV-2 pathogenicity. Consequently, new data can be used to advance the molecular understanding of infection. present bioinformatics study discusses "spikeopathy" at level and focuses possible post-transcriptional regulation spike protein S1 subunit in host cell/tissue. A theoretical protein-RNA recognition code was check compatibility with mRNAs human transcriptome (1-L transcription). principle for this method is elucidated defined RNA binding GEMIN5 (gem nuclear organelle-associated 5) RNU2-1 (U2 spliceosomal RNA). Using described here, it shown that 45% genes/proteins identified by 1-L transcription are directly linked COVID-19, 39% indirectly 16% cannot currently associated COVID-19. stroke, diabetes, cardiac injury.

Language: Английский

Citations

1
Humanized L184Q Mutated Surfactant Protein C Gene Alters Alveolar Type 2 Epithelial Cell Fate DOI Open Access
Krishan Gopal Jain, Yang Liu,

Runzhen Zhao

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8723 - 8723

Published: Aug. 9, 2024

Alveolar type 2 epithelial (AT2) cells synthesize surfactant protein C (SPC) and repair an injured alveolar epithelium. A mutated gene (SftpcL184Q, Gene ID: 6440) in newborns has been associated with respiratory distress syndrome pulmonary fibrosis. However, the underlying mechanisms causing Sftpc mutations to regulate AT2 lineage remain unclear. We utilized three-dimensional (3D) feeder-free organoids vitro simulate epithelium compared characteristics between WT (C57BL/6) SftpcL184Q mutant mice using colony formation assays, immunofluorescence, flow cytometry, qRT-PCR, Western blot assays. The numbers were reduced significantly mice. Organoid colony-forming efficiency attenuated 3D cultures of primary those Podoplanin (PDPN, 1 cell (AT1) marker) expression transient count was increased levels CD74, heat shock 90 (HSP90), ribosomal S3A1 (RPS3A1) not different cells. This study demonstrated that humanized mutation regulates intrinsically. regulation is independent HSP90, RPS3A1 pathways.

Language: Английский

Citations

1
Heat shock protein 90 inhibition in the endothelium DOI Creative Commons
Nektarios Barabutis

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Sept. 4, 2023

OPINION article Front. Med., 04 September 2023Sec. Translational Medicine Volume 10 - 2023 | https://doi.org/10.3389/fmed.2023.1255488

Language: Английский

Citations

2
Litopenaeus vannamei heat shock protein 90 (LvHSP90) interacts with white spot syndrome virus protein, WSSV322, to modulate hemocyte apoptosis during viral infection DOI

Warumporn Yingsunthonwattana,

Pakkakul Sangsuriya,

Premruethai Supungul

et al.

Fish & Shellfish Immunology, Journal Year: 2024, Volume and Issue: 151, P. 109695 - 109695

Published: June 12, 2024

Language: Английский

Citations

0
Inflammatory response to sars-CoV 2 and other respiratory viruses DOI
André Emilio Viñán Garcés, Eder Cáceres,

Juan Olivella Gómez

et al.

Expert Review of Anti-infective Therapy, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 14

Published: Sept. 4, 2024

Lower respiratory tract infections (LRTI) remain a significant global cause of mortality and disability. Viruses constitute substantial proportion LRTI cases, with their pandemic potential posing latent threat. After the SARS-CoV-2 pandemic, resurgence other viruses, including Influenza Respiratory Syncytial Virus responsible for has been observed especially in susceptible populations.

Language: Английский

Citations

0
The heat shock protein 90 inhibitor RGRN-305 attenuates SARS-CoV-2 spike protein-induced inflammation in vitro but lacks effectiveness as COVID-19 treatment in mice DOI Creative Commons
Hakim Ben Abdallah,

Giorgia Marino,

Manja Idorn

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(9), P. e0310915 - e0310915

Published: Sept. 26, 2024

The inhibition of heat shock protein 90 (HSP90), a molecular chaperone, has been proposed to be potential novel treatment strategy for Coronavirus disease 2019 (COVID-19). In contrast other studies, our data demonstrated that RGRN-305, HSP90 inhibitor, exacerbated the cytopathic effect and did not reduce viral shedding in VeroE6-hTMPRSS2 cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Likewise murine model SARS-CoV-2, transgenic mice treated orally RGRN-305 exhibited reduced survival by end experiment (day 12) as 14% (1/7) survived compared 63% (5/8) those drug-vehicle. Animal weight was treatment. Interestingly, we significantly dampened inflammatory response induced SARS-CoV-2 spike human macrophage-like (U937) lung epithelial (A549). Measured quantitative real-time PCR, mRNA expression proinflammatory cytokines TNF , IL1B IL6 were reduced. Together, these suggest exacerbates infection vitro reduces but exhibits strong anti-inflammatory properties. This shows while may helpful ‘cytokine storm’, it no beneficial impact on replication or animals monotherapy. Further animal studies inhibitors combination an anti-viral drug provide additional insights into its utility infections whether continue COVID-19 disease.

Language: Английский

Citations

0