Methods of An Open-Label Proof-Of-Concept Trial of Intravenous Valproic Acid for Severe COVID-19

Chiquete, Erwin; Toapanta‐Yanchapaxi, Liz; Cantú-Brito, Carlos

doi:10.1101/2020.04.26.20079988

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…The reported side effects like hepatotoxicity and teratogenicity are mainly associated with the parental compound valproate and can be avoided by the use of its derivatives like Valpromide (VPD) and valnoctamide (VCD). A recent open-label proof-of-concept trial of 10 days Intravenous Valproic Acid for Severe COVID-19 showed a 50% reduction in the case fatality rate and length of stay (38). More studies are needed to explore the promising potential of valproic acid in the treatment of COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells

et al. 2020

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Current guidelines for COVID-19 management recommend the utilization of various repurposed drugs. Despite ongoing research toward the development of a vaccine against SARS-CoV-2, such a vaccine will not be available in time to contribute to the containment of the ongoing pandemic. Therefore, there is an urgent need to develop a framework for the rapid identification of novel targets for diagnostic and therapeutic interventions. We analyzed publicly available transcriptomic datasets of SARS-CoV infected humans and mammals to identify consistent differentially expressed genes then validated in SARS-CoV-2 infected epithelial cells transcriptomic datasets. Comprehensive toxicogenomic analysis of the identified genes to identify possible interactions with clinically proven drugs was carried out. We identified IFITM3 as an early upregulated gene, and valproic acid was found to enhance its mRNA expression as well as induce its antiviral action. These findings indicate that analysis of publicly available transcriptomic and toxicogenomic data represents a rapid approach for the identification of novel targets and molecules that can modify the action of such targets during the early phases of emerging infections like COVID-19.

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Section: Discussionmentioning

confidence: 99%

Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells

et al. 2020

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“…The results of this study suggest that glutathione may also interact with viral proteins. Valproic acid is a short chain fatty acid with antiviral activity against several viruses ( 42 , 43 ) and might also be effective against SARS-CoV-2 ( 44 , 45 , 46 ). Therefore, the network- and sequence similarity-based methods identified compounds that may limit viral activities.…”

Section: Discussionmentioning

confidence: 99%

A systems-based method to repurpose marketed therapeutics for antiviral use: a SARS-CoV-2 case study

Wang¹,

Withers²,

Ricchiuto³

et al. 2021

Life Sci. Alliance

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This study describes two complementary methods that use network-based and sequence similarity tools to identify drug repurposing opportunities predicted to modulate viral proteins. This approach could be rapidly adapted to new and emerging viruses. The first method built and studied a virus–host–physical interaction network; a three-layer multimodal network of drug target proteins, human protein–protein interactions, and viral–host protein–protein interactions. The second method evaluated sequence similarity between viral proteins and other proteins, visualized by constructing a virus–host–similarity interaction network. Methods were validated on the human immunodeficiency virus, hepatitis B, hepatitis C, and human papillomavirus, then deployed on SARS-CoV-2. Comparison of virus–host–physical interaction predictions to known antiviral drugs had AUCs of 0.69, 0.59, 0.78, and 0.67, respectively, reflecting that the scores are predictive of effective drugs. For SARS-CoV-2, 569 candidate drugs were predicted, of which 37 had been included in clinical trials for SARS-CoV-2 (AUC = 0.75, P-value 3.21 × 10−3). As further validation, top-ranked candidate antiviral drugs were analyzed for binding to protein targets in silico; binding scores generated by BindScope indicated a 70% success rate.

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Hidden pharmacological activities of valproic acid: A new insight

Singh¹,

Gupta²,

Verma³

et al. 2021

Biomedicine & Pharmacotherapy

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Methods of An Open-Label Proof-Of-Concept Trial of Intravenous Valproic Acid for Severe COVID-19

Abstract: word count: 254 Text word count: 1680

Cited by 3 publications

References 24 publications

Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells

Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells

A systems-based method to repurpose marketed therapeutics for antiviral use: a SARS-CoV-2 case study

Hidden pharmacological activities of valproic acid: A new insight

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