The AI-discovered aetiology of COVID-19 and rationale of the irinotecan+ etoposide combination therapy for critically ill COVID-19 patients

Lovetrue, Bragi

doi:10.1016/j.mehy.2020.110180

Cited by 24 publications

(14 citation statements)

References 22 publications

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“…14 Second, it has been shown to suppress RNA virus replication in in vitro studies. 15 The combination of etoposide and dexamethasone also has been shown to be successful in the treatment of hyperinflammatory syndromes associated with other viral illnesses such as severe swine flu A/H1N1, and avian influenza A/H5N1 infections. 16,17 In addition, our modified dose of 50 mg/m 2 was based on aforementioned Swine influenza A/H1N1-related hyperinflammatory syndromes in the elderly.…”

Section: Discussionmentioning

confidence: 99%

Etoposide as Salvage Therapy for Cytokine Storm Due to Coronavirus Disease 2019

Patel

Dominguez

Sacher

et al. 2021

Chest

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COVID-19 has resulted in significant morbidity and mortality due to lack of effective therapies. Therapeutic strategies under investigation target the overactive cytokine response with anti-cytokine or immunomodulators therapies. We present a unique case of severe cytokine storm resistant to multiple anti-cytokine therapies, but eventually responsive to Etoposide. Thus, Etoposide may have a role as salvage therapy in treatment of cytokine storm in COVID-19. To our knowledge, this is the first reported case of use of Etoposide in COVID-19.

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Section: Discussionmentioning

confidence: 99%

Etoposide as Salvage Therapy for Cytokine Storm Due to Coronavirus Disease 2019

Patel

Dominguez

Sacher

et al. 2021

Chest

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“…In animal experiments, estrogen therapy suppressed inflammatory reactions and cured COVID-19 infection (54).Based on the results of this study, olaparib and irinotecan had a suitable free binding energy with CD147 ( Table 3 ). A relevant study demonstrated that a combination of irinotecan (topoisomerase I inhibitor) and etoposide (a topoisomerase II inhibitor) can potentially inhibit cytokine storms in COVID-19 ( 55 ). A type of clinical study using a drug repositioning strategy indicated the inhibitory effects of olaparib and mefuparib, as two PARP1 inhibitors, on COVID-19 ( 56 ).…”

Section: - Discussionmentioning

confidence: 99%

Repurposing FDA-approved drugs to fight COVID-19 using in silico methods: Targeting SARS-CoV-2 RdRp enzyme and host cell receptors (ACE2, CD147) through virtual screening and molecular dynamic simulations

Mahdian

Zarrabi

Panahi

et al. 2021

Informatics in Medicine Unlocked

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Background Different approaches have been proved effective for combating the COVID-19 pandemic. Accordingly, in silico drug repurposing strategy, has been highly regarded as an accurate computational tool to achieve fast and reliable results. Considering SARS-CoV-2's structural proteins and their interaction the host's cell-specific receptors, this study investigated a drug repurposing strategy aiming to screen compatible inhibitors of FDA-approved drugs against viral entry receptors (ACE2 and CD147) and integral enzyme of the viral polymerase (RdRp). Methods The study screened the FDA-approved drugs against ACE2, CD147, and RDRP by virtual screening and molecular dynamics (MD) simulation. Results The results of this study indicated that five drugs with ACE2, four drugs with RDRP , and seven drugs with CD147 achieved the most favorable free binding energy (ΔG < -10). This study selected these drugs for MD simulation investigation whose results demonstrated that ledipasvir with ACE2, estradiol benzoate with CD147, and vancomycin with RDRP represented the most favorable ΔG. Also, paritaprevir and vancomycin have good binding energy with both targets (ACE2 and RdRp). Conclusions Ledipasvir, estradiol benzoate, and vancomycin and paritaprevir are potentially suitable candidates for further investigation as possible treatments of COVID-19 and novel drug development.

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“…Our combined machine learning and docking strategy return high binding affinity ligands consistent with previous computational screens of the ACE2 receptor. Furthermore, sorafinib, [ 42 ] irinotecan, [ 43 ] and nilotinib [ 44 ] ( Table S1 ) show reduction in infection rates in cell assays studies, while zanubrutinib is currently in clinical trial. Although these drugs target other pathways involved in the pathology, the reduction in infection rate could be in part attributed to the ability of the drug to bind ACE2.…”

Section: Resultsmentioning

confidence: 99%

Predicting Potential SARS-COV-2 Drugs—In Depth Drug Database Screening Using Deep Neural Network Framework SSnet, Classical Virtual Screening and Docking

Karki

Verma

Trozzi

et al. 2021

IJMS

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Severe Acute Respiratory Syndrome Corona Virus 2 has altered life on a global scale. A concerted effort from research labs around the world resulted in the identification of potential pharmaceutical treatments for CoVID-19 using existing drugs, as well as the discovery of multiple vaccines. During an urgent crisis, rapidly identifying potential new treatments requires global and cross-discipline cooperation, together with an enhanced open-access research model to distribute new ideas and leads. Herein, we introduce an application of a deep neural network based drug screening method, validating it using a docking algorithm on approved drugs for drug repurposing efforts, and extending the screen to a large library of 750,000 compounds for de novo drug discovery effort. The results of large library screens are incorporated into an open-access web interface to allow researchers from diverse fields to target molecules of interest. Our combined approach allows for both the identification of existing drugs that may be able to be repurposed and de novo design of ACE2-regulatory compounds. Through these efforts we demonstrate the utility of a new machine learning algorithm for drug discovery, SSnet, that can function as a tool to triage large molecular libraries to identify classes of molecules with possible efficacy.

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The AI-discovered aetiology of COVID-19 and rationale of the irinotecan+ etoposide combination therapy for critically ill COVID-19 patients

Cited by 24 publications

References 22 publications

Etoposide as Salvage Therapy for Cytokine Storm Due to Coronavirus Disease 2019

Etoposide as Salvage Therapy for Cytokine Storm Due to Coronavirus Disease 2019

Repurposing FDA-approved drugs to fight COVID-19 using in silico methods: Targeting SARS-CoV-2 RdRp enzyme and host cell receptors (ACE2, CD147) through virtual screening and molecular dynamic simulations

Predicting Potential SARS-COV-2 Drugs—In Depth Drug Database Screening Using Deep Neural Network Framework SSnet, Classical Virtual Screening and Docking

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