Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?

Hashemian, Seyed Mohammad Reza; Sheida, Amirhossein; Taghizadieh, Mohammad; Memar, Mohammad Yousef; Hamblin, Michael R.; Baghi, Hossein Bannazadeh; Nahand, Javid Sadri; Asemi, Zatollah; Mirzaei, Hamed

doi:10.1016/j.biopha.2023.114367

Cited by 78 publications

(38 citation statements)

References 79 publications

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“…72 The major safety concern of paxlovid is related to the ritonavir molecule, which increases significantly the concentration of drugs metabolized by CYP3A in patients with underlying disorders. 73 This concern is more critical for transplant patients who are receiving substrates of CYP3A such as tacrolimus and cyclosporine. 74…”

Section: Paxlovid (Nirmatrelvir Plus Ritonavir)mentioning

confidence: 99%

“…In terms of toxicity and side effects, it can be expressed that paxlovid is a drug with an acceptable safety profile (especially in the case of the nirmatrelvir molecule, for which no concerning side effects have been reported) . The major safety concern of paxlovid is related to the ritonavir molecule, which increases significantly the concentration of drugs metabolized by CYP3A in patients with underlying disorders . This concern is more critical for transplant patients who are receiving substrates of CYP3A such as tacrolimus and cyclosporine …”

Section: Anti-covid-19 Drugsmentioning

confidence: 99%

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An Overview on Anti-COVID-19 Drug Achievements and Challenges Ahead

Valipour,

Irannejad,

Keyvani

2023

ACS Pharmacol. Transl. Sci.

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The appearance of several coronavirus pandemics/ epidemics during the last two decades (SARS-CoV-1 in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019) indicates that humanity will face increasing challenges from coronaviruses in the future. The emergence of new strains with similar transmission characteristics as SARS-CoV-2 and mortality rates similar to SARS-CoV-1 (∼10% mortality) or MERS-CoV (∼35% mortality) in the future is a terrifying possibility. Therefore, getting enough preparations to face such risks is an inevitable necessity. The present study aims to review the drug achievements and challenges in the fight against SARS-CoV-2 with a combined perspective derived from pharmacology, pharmacotherapy, and medicinal chemistry insights. Appreciating all the efforts made during the past few years, there is strong evidence that the desired results have not yet been achieved and research in this area should still be pursued seriously. By expressing some pessimistic possibilities and concluding that the drug discovery and pharmacotherapy of COVID-19 have not been successful so far, this short essay tries to draw the attention of responsible authorities to be more prepared against future coronavirus epidemics/pandemics.

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Section: Paxlovid (Nirmatrelvir Plus Ritonavir)mentioning

confidence: 99%

Section: Anti-covid-19 Drugsmentioning

confidence: 99%

An Overview on Anti-COVID-19 Drug Achievements and Challenges Ahead

Valipour,

Irannejad,

Keyvani

2023

ACS Pharmacol. Transl. Sci.

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“…It is combined with another antiviral drug called ritonavir, which helps to increase the levels of NIRM in the body. This combination drug is also given orally to patients who are at risk of developing severe COVID-19 symptoms. , These drugs pose significant environmental hazards due to their widespread usage. They persist in the environment as they enter domestic sewage through human feces and urine, which makes it difficult for municipal sewage treatment facilities to eliminate them effectively, thus posing a risk to human and animal health .…”

Section: Introductionmentioning

confidence: 99%

Insights into the Adsorption Properties of Mixed Matrix Membranes (Pebax 1657-g-Chitosan-PVDF-Bovine Serum Albumin@ZIF-CO₃-1) for the Antiviral COVID-19 Treatment Drugs Remdesivir and Nirmatrelvir: An In Silico Study

Salahshoori,

Montazeri,

Yazdanbakhsh

et al. 2023

ACS Appl. Mater. Interfaces

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The effect of the COVID-19 pandemic on the accumulation of environmental pollutants has been significant. In that way, waste management systems have faced problems, and the amount of hazardous and medical wastes has increased. As pharmaceuticals associated with the treatment of COVID-19 enter the environment, aquatic and terrestrial ecosystems have been negatively impacted, potentially disrupting natural processes and harming aquatic life. This analysis seeks to appraise the potential of mixed matrix membranes (MMMs) composed of Pebax 1657-g-chitosan-polyvinylidene fluoride (PEX-g-CHS-PVDF)-bovine serum albumin (BSA)@ZIF-CO 3 -1 as adsorbents for removing remdesivir (REMD) and nirmatrelvir (NIRM) from aqueous environments. An in silico study was conducted to explore the adsorption characteristics, physicochemical properties, and structural features of these MMMs, employing quantum mechanical (QM) calculations, molecular dynamics (MD) simulations, and Monte Carlo (MC) simulations as research methodologies. Incorporating BSA@ZIF-CO 3 -1 into the PEX-g-CHS-PVDF polymer matrix improved the physicochemical properties of MMMs by promoting the compatibility and interfacial adhesion between the two materials, facilitated by electrostatic interactions, van der Waals forces, and hydrogen bonding. Investigation of the interaction mechanism between the title pharmaceutical pollutants and the surfaces of MMMs, along with the description of their adsorption behavior, was also conducted by applying MD and MC approaches. Our observations indicate that the adsorption behavior of REMD and NIRM is influenced by molecular size, shape, and the presence of functional groups. Molecular simulation analysis demonstrated that the MMM membrane is a highly suitable adsorbent for the adsorption of REMD and NIRM drugs, with a higher affinity toward REMD adsorption. Our study emphasizes the significance of computational modeling in developing practical strategies for eliminating COVID-19 drug contaminants from wastewater. The knowledge obtained through our molecular simulations and QM calculations can assist in creating more efficient adsorption materials, resulting in a cleaner and healthier environment.

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“…Current evidence has shown the effectiveness of nirmatrelvir/ritonavir (Paxlovid) and molnupiravir treatments in improving clinical outcomes in COVID‐19 patients 13–15 . Nirmatrelvir/ritonavir is a combination of two compounds, nirmatlavir which can inhibit the main protease of SARS‐CoV‐2 and ritonavir which increases plasma concentrations of nirmatrelvir by targeting CYP3A4 16 . The US Food and Drug Administration (FDA) has approved nirmatrelvir/ritonavir for the treatment of mild to moderate COVID‐19 in adults and children aged 12 or older 17 .…”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15] Nirmatrelvir/ritonavir is a combination of two compounds, nirmatlavir which can inhibit the main protease of SARS-CoV-2 and ritonavir which increases plasma concentrations of nirmatrelvir by targeting CYP3A4. 16 The US Food and Drug Administration (FDA) has approved nirmatrelvir/ritonavir for the treatment of mild to moderate COVID-19 in adults and children aged 12 or older. 17 Molnupiravir (Lagevrio) is an FDA-approved antiviral agent for the treatment of mildto-moderate COVID-19 capable of inhibiting the replication of RNA viruses through viral error induction.…”

Section: Introductionmentioning

confidence: 99%

Comparative efficacy and safety of nirmatrelvir/ritonavir and molnupiravir for COVID‐19: A systematic review and meta‐analysis

Amani

Akbarzadeh

Amani

et al. 2023

Journal of Medical Virology

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This study aimed to compare the efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) with molnupiravir in the treatment of coronavirus disease 2019 . To end this, PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar were systematically searched to collect relevant evidence up to February 15, 2023. The risk of bias was evaluated using the risk of bias in nonrandomized studies of interventions tool. Data were analyzed using Comprehensive Meta-Analysis software. Eighteen studies involving 57 659 patients were included in the meta-analysis. The meta-analysis showed a significant difference between nirmatrelvir/ritonavir and molnupiravir in terms of all-cause mortality rate (odds ratio [OR] = 0.54, 95% confidence interval [CI]: 0.44-0.67), all-cause hospitalization rate (OR = 0.61, 95% CI: 0.54-0.69), death or hospitalization rate (OR = 0.61, 95% CI: 0.38-0.99), and negative polymerase chain reaction conversion time (mean difference = −1.55, 95% CI: −1.74 to −1.37). However, no significant difference was observed between the two groups in terms of COVID-19 rebound (OR = 0.87, 95% CI: 0.71-1.07). In terms of safety, although the incidence of any adverse events was higher in the nirmatrelvir/ritonavir group (OR = 2.52, 95% CI:1.57-4.06), no significant difference was observed between the two treatments in terms of adverse events leading to treatment discontinuation (OR = 1.18, 95% CI: 0.69-2.00). The present meta-analysis demonstrated the significant superiority of nirmatrelvir/ritonavir over molnupiravir in improving clinical efficacy in COVID-19 patients during the prevalence of Omicron variant. These findings, however, need to be further confirmed.

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Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?

Cited by 78 publications

References 79 publications

An Overview on Anti-COVID-19 Drug Achievements and Challenges Ahead

An Overview on Anti-COVID-19 Drug Achievements and Challenges Ahead

Insights into the Adsorption Properties of Mixed Matrix Membranes (Pebax 1657-g-Chitosan-PVDF-Bovine Serum Albumin@ZIF-CO₃-1) for the Antiviral COVID-19 Treatment Drugs Remdesivir and Nirmatrelvir: An In Silico Study

Comparative efficacy and safety of nirmatrelvir/ritonavir and molnupiravir for COVID‐19: A systematic review and meta‐analysis

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Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?

Cited by 78 publications

References 79 publications

An Overview on Anti-COVID-19 Drug Achievements and Challenges Ahead

An Overview on Anti-COVID-19 Drug Achievements and Challenges Ahead

Insights into the Adsorption Properties of Mixed Matrix Membranes (Pebax 1657-g-Chitosan-PVDF-Bovine Serum Albumin@ZIF-CO3-1) for the Antiviral COVID-19 Treatment Drugs Remdesivir and Nirmatrelvir: An In Silico Study

Comparative efficacy and safety of nirmatrelvir/ritonavir and molnupiravir for COVID‐19: A systematic review and meta‐analysis

Contact Info

Product

Resources

About

Insights into the Adsorption Properties of Mixed Matrix Membranes (Pebax 1657-g-Chitosan-PVDF-Bovine Serum Albumin@ZIF-CO₃-1) for the Antiviral COVID-19 Treatment Drugs Remdesivir and Nirmatrelvir: An In Silico Study