Disease-drug and drug-drug interaction in COVID-19: Risk and assessment

Kumar, Devendra; Trivedi, Neerja

doi:10.1016/j.biopha.2021.111642

Cited by 63 publications

(65 citation statements)

References 315 publications

(166 reference statements)

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“…Thus, it is indispensable to survey the drug interactions and to carefully evaluate the appropriate treatment strategy against SARS-CoV-2. While clinical data from healthy donors showed that remdesivir and its metabolite GS-4412524 are metabolized through Cytochromes P450 (CYPs) enzymes (CYP2C8, CYP2D6, and CYP3A4), clinical studies that examined drug–drug interactions were not yet complete, although the mathematical prediction of DDI liability suggested that remdesivir and GS-441524 might elevate the levels of co-prescribed drugs that depend on these CYP enzymes [ 61 , 62 , 63 ]. However, the influence of remdesivir on CYP-enzyme dependent metabolism is suggested to be weak [ 61 , 63 ].…”

Section: Discussionmentioning

confidence: 99%

“…While clinical data from healthy donors showed that remdesivir and its metabolite GS-4412524 are metabolized through Cytochromes P450 (CYPs) enzymes (CYP2C8, CYP2D6, and CYP3A4), clinical studies that examined drug–drug interactions were not yet complete, although the mathematical prediction of DDI liability suggested that remdesivir and GS-441524 might elevate the levels of co-prescribed drugs that depend on these CYP enzymes [ 61 , 62 , 63 ]. However, the influence of remdesivir on CYP-enzyme dependent metabolism is suggested to be weak [ 61 , 63 ]. Thus, simultaneous administration with fluoxetine, another known inhibitor of CYPs (CYP2D6 and CYP2C9/10) should be carefully monitored [ 64 , 65 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

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Combination Therapy with Fluoxetine and the Nucleoside Analog GS-441524 Exerts Synergistic Antiviral Effects against Different SARS-CoV-2 Variants In Vitro

et al. 2021

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The ongoing SARS-CoV-2 pandemic requires efficient and safe antiviral treatment strategies. Drug repurposing represents a fast and low-cost approach to the development of new medical treatment options. The direct antiviral agent remdesivir has been reported to exert antiviral activity against SARS-CoV-2. Whereas remdesivir only has a very short half-life time and a bioactivation, which relies on pro-drug activating enzymes, its plasma metabolite GS-441524 can be activated through various kinases including the adenosine kinase (ADK) that is moderately expressed in all tissues. The pharmacokinetics of GS-441524 argue for a suitable antiviral drug that can be given to patients with COVID-19. Here, we analyzed the antiviral property of a combined treatment with the remdesivir metabolite GS-441524 and the antidepressant fluoxetine in a polarized Calu-3 cell culture model against SARS-CoV-2. The combined treatment with GS-441524 and fluoxetine were well-tolerated and displayed synergistic antiviral effects against three circulating SARS-CoV-2 variants in vitro in the commonly used reference models for drug interaction. Thus, combinatory treatment with the virus-targeting GS-441524 and the host-directed drug fluoxetine might offer a suitable therapeutic treatment option for SARS-CoV-2 infections.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Combination Therapy with Fluoxetine and the Nucleoside Analog GS-441524 Exerts Synergistic Antiviral Effects against Different SARS-CoV-2 Variants In Vitro

et al. 2021

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“…However, in some cases, the opposite results can occur. For instance, in the first wave of COVID-19, chloroquine (CQ) and hydroxychloroquine (HCQ), which are well-known antimalarial drugs, were recommended as a primary treatment option for COVID-19 [146][147][148]. However, later in the pandemic, well-designed randomized controlled trials confirmed that the CQ/HCQ regimen does not provide any clinical benefit for COVID-19 patients [149].…”

Section: Therapeutics For Covid-19 Treatmentmentioning

confidence: 99%

A Multidisciplinary Approach to Coronavirus Disease (COVID-19)

Ertürk

Şahin

et al. 2021

Molecules

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Since December 2019, humanity has faced an important global threat. Many studies have been published on the origin, structure, and mechanism of action of the SARS-CoV-2 virus and the treatment of its disease. The priority of scientists all over the world has been to direct their time to research this subject. In this review, we highlight chemical studies and therapeutic approaches to overcome COVID-19 with seven different sections. These sections are the structure and mechanism of action of SARS-CoV-2, immunotherapy and vaccine, computer-aided drug design, repurposing therapeutics for COVID-19, synthesis of new molecular structures against COVID-19, food safety/security and functional food components, and potential natural products against COVID-19. In this work, we aimed to screen all the newly synthesized compounds, repurposing chemicals covering antiviral, anti-inflammatory, antibacterial, antiparasitic, anticancer, antipsychotic, and antihistamine compounds against COVID-19. We also highlight computer-aided approaches to develop an anti-COVID-19 molecule. We explain that some phytochemicals and dietary supplements have been identified as antiviral bioproducts, which have almost been successfully tested against COVID-19. In addition, we present immunotherapy types, targets, immunotherapy and inflammation/mutations of the virus, immune response, and vaccine issues.

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“…However, CYP3A induction caused by rifampicin exposure is expected to reduce RDV levels by 30%, and inhibition of CYP3A can increase blood levels by only 4%. Moreover, an antagonistic effect of chloroquine on the intracellular activation and antiviral activity of RDV has been reported, making co-administration of these two drugs unsuitable, based on in vitro data [ 55 ]. Another relevant aspect in terms of drug interactions can be reported in selected populations, such as those receiving antiepileptic drugs (carbamazepine, phenobarbital, and phenytoin), which induce CYP 3A4 and theoretically reduce RDV levels [ 53 ].…”

Section: Pharmacokinetics Of Rdv and Drug Interactionsmentioning

confidence: 99%

An overview of the preclinical discovery and development of remdesivir for the treatment of coronavirus disease 2019 (COVID-19)

Pagliano

Sellitto

Scarpati

et al. 2021

Expert Opinion on Drug Discovery

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Introduction Remdesivir (RDV) is an inhibitor of the viral RNA-dependent RNA polymerases that are active in some RNA viruses, including the Ebola virus and zoonotic coronaviruses. When severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent of the coronavirus disease 2019 (COVID-19), several investigations have assessed the potential activity of RDV in inhibiting viral replication, giving rise to hope for an effective treatment. Areas covered In this review, the authors describe the main investigations leading to the discovery of RDV and its subsequent development as an antiviral agent, focusing on the main clinical trials investigating its efficacy in terms of symptom resolution and mortality reduction. Expert opinion RDV is the most widely investigated antiviral drug for the treatment of COVID-19. This attention on RDV activity against SARS-CoV-2 is justified by promising in vitro studies, which demonstrated that RDV was able to suppress viral replication without significant toxicity. Such activity was confirmed by an investigation in an animal model and by the results of preliminary clinical investigations. Nevertheless, the efficacy of RDV in reducing mortality has not been clearly demonstrated.

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Disease-drug and drug-drug interaction in COVID-19: Risk and assessment

Cited by 63 publications

References 315 publications

Combination Therapy with Fluoxetine and the Nucleoside Analog GS-441524 Exerts Synergistic Antiviral Effects against Different SARS-CoV-2 Variants In Vitro

Combination Therapy with Fluoxetine and the Nucleoside Analog GS-441524 Exerts Synergistic Antiviral Effects against Different SARS-CoV-2 Variants In Vitro

A Multidisciplinary Approach to Coronavirus Disease (COVID-19)

An overview of the preclinical discovery and development of remdesivir for the treatment of coronavirus disease 2019 (COVID-19)

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