Immunopharmacological management of COVID-19: Potential therapeutic role of valproic acid

Ünal, Gökhan; Turan, Bahadır; Balcıoğlu, Yasin Hasan

doi:10.1016/j.mehy.2020.109891

Cited by 17 publications

(19 citation statements)

References 13 publications

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“…We proposed 18 drugs and 30 drug combinations including broad-spectrum antiviral agents, receptor antagonists, channel blockers, and renin-angiotensin system agents. Some medications such as dexamethasone, chloroquine, curcumin [41], glyburide [42], tretinoin [43,44], cyclosporine [45,46], valproic acid [47], fostamatinib [48,49], atorvastatin [50][51][52], and phenethyl-isothiocyanate [53] have recently received major attention for the treatment of COVID-19 and have been validated by previous studies, supporting the reliability of our findings. Nicardipine, promethazine, orantinib, and tipifarnib have not previously been reported as potential treatments for COVID-19.…”

Section: Discussionsupporting

confidence: 88%

Drug Repurposing for COVID-19 Treatment by Integrating Network Pharmacology and Transcriptomics

Liu

Liang

et al. 2021

Pharmaceutics

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Since coronavirus disease 2019 (COVID-19) is a serious new worldwide public health crisis with significant morbidity and mortality, effective therapeutic treatments are urgently needed. Drug repurposing is an efficient and cost-effective strategy with minimum risk for identifying novel potential treatment options by repositioning therapies that were previously approved for other clinical outcomes. Here, we used an integrated network-based pharmacologic and transcriptomic approach to screen drug candidates novel for COVID-19 treatment. Network-based proximity scores were calculated to identify the drug–disease pharmacological effect between drug–target relationship modules and COVID-19 related genes. Gene set enrichment analysis (GSEA) was then performed to determine whether drug candidates influence the expression of COVID-19 related genes and examine the sensitivity of the repurposing drug treatment to peripheral immune cell types. Moreover, we used the complementary exposure model to recommend potential synergistic drug combinations. We identified 18 individual drug candidates including nicardipine, orantinib, tipifarnib and promethazine which have not previously been proposed as possible treatments for COVID-19. Additionally, 30 synergistic drug pairs were ultimately recommended including fostamatinib plus tretinoin and orantinib plus valproic acid. Differential expression genes of most repurposing drugs were enriched significantly in B cells. The findings may potentially accelerate the discovery and establishment of an effective therapeutic treatment plan for COVID-19 patients.

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Section: Discussionsupporting

confidence: 88%

Drug Repurposing for COVID-19 Treatment by Integrating Network Pharmacology and Transcriptomics

Liu

Liang

et al. 2021

Pharmaceutics

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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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“…It inhibits viral replication by reducing RNAdependent virus RNA polymerase [55,56] and cell surface binding [56]. Valproate also has systemic and pulmonary anti-inflammatory effects [55,57]. Injection of SARS-CoV spike protein into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway, suggesting that ARBs and ACE-I are a potential therapy to prevent the cytokine storm and acute respiratory distress syndrome associated with severe COVID-19 [58,59].…”

Section: Potential Treatments Of Covid-19 Relevant To Migraine: Intermentioning

confidence: 99%

“…Valproic acid could potentially be repurposed for its anti-viral and anti-inflammatory actions. It inhibits viral replication by reducing RNA-dependent virus RNA polymerase [ 55 , 56 ] and cell surface binding [ 56 ]. Valproate also has systemic and pulmonary anti-inflammatory effects [ 55 , 57 ].…”

Section: Potential Treatments Of Covid-19 Relevant To Migraine: Intermentioning

confidence: 99%

Navigating migraine care through the COVID-19 pandemic: an update

Angus‐Leppan

Guiloff

Benson³

et al. 2021

J Neurol

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The worldwide treatment gap for migraine before COVID-19 inevitably widens as attention focuses on an international emergency. Migraine hits people particularly in their early and middle years, potentially reduces quality of life and productivity, and remains a common emergency presentation. This article examines the impact of COVID-19 on migraine, and changing aspects of migraine care during and after the pandemic. Many risk factors for severe COVID-19-older age, male gender, cardiac and respiratory diseases, diabetes, obesity, and immunosuppression-are less frequent in migraineurs. Telemedicine is effective for migraine follow-up, and needs ongoing evaluation. Most migraine treatments can start or continue in acute COVID-19, with care to avoid drug interactions. Close contact procedures (botulinum toxin, acupuncture and steroid injections) are avoided in lockdown or in the vulnerable. Secondary effects of COVID-19, including long COVID and its economic impact, are probably equal or greater in people with migraine. Migraine and other long-term conditions need adequate resourcing to prevent personal, social and economic suffering. Treating migraine, a sequel of COVID, potentially reduces the impact of long COVID.

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Immunopharmacological management of COVID-19: Potential therapeutic role of valproic acid

Cited by 17 publications

References 13 publications

Drug Repurposing for COVID-19 Treatment by Integrating Network Pharmacology and Transcriptomics

Drug Repurposing for COVID-19 Treatment by Integrating Network Pharmacology and Transcriptomics

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

Navigating migraine care through the COVID-19 pandemic: an update

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