- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: Molecular dynamic simulations to explore the broad-spectrum activity of (Pubmed Central) - Dec 1, 2024
Analyses of residue BFE decomposition reveals Cys145 as a pivotalt amino acid, positively influencing the stable binding between Mpros and inhibitor. These finding imply that PF-07321332 has the potential to be an effective anti-coronavirus inhibitor and also provide insights into inhibitor optimization and drug design strategies against human coronavirus.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Journal: Network pharmacology and molecular docking identified IL-6 as a critical target of Qing Yan He Ji against COVID-19. (Pubmed Central) - Nov 29, 2024
Molecular dynamics simulation was performed for molecular docking results, showing IL-6-(4aS,6aR,6aS,6bR,8aR,10R,12aR,14bS)-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid (4aS) complex, IL-6-stigmasterol complex, IL-6-poriferasterol complex, IL-6-sitosterol complex, and IL-6-beta-sitosterol complex had relatively good binding stability. In conclusion, the multi-component and multi-target intervention of QYHJ against COVID-19 is closely related to antiviral and anti-inflammatory activities, which provides a theoretical basis for clinical application.
- |||||||||| Xiannuoxin (simnotrelvir) / Simcere, Shanghai Inst. of Materia Medica, Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: Potency Prediction of Covalent Inhibitors against SARS-CoV-2 3CL-like Protease and Multiple Mutants by Multiscale Simulations. (Pubmed Central) - Nov 28, 2024
Such a change is inhibitor dependent, corresponding to varied levels of drug resistance of these 3CLpro mutants against nirmatrelvir and simnotrelvir and no resistance to the 11a compound. These results together suggest that the present simulations with a suitable protocol can efficiently evaluate the reactivity and potency of covalent inhibitors along with the elucidated molecular mechanisms of covalent inhibition.
- |||||||||| Review, Journal: Proline Analogues in Drug Design: Current Trends and Future Prospects. (Pubmed Central) - Nov 28, 2024
Additionally, we discuss several intriguing cases where nonproline residues were replaced with proline analogues as a strategy to eliminate unwanted hydrogen bond donor sites. In conclusion, we present some suggestions for the future exploration of this promising class of molecular entities in drug discovery.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal, Real-world evidence, Real-world: Nirmatrelvir/ritonavir: real world drug-drug interaction management experience. (Pubmed Central) - Nov 28, 2024
Among 208 who received NMV/r therapy, we identified 184 potential DDIs, 8% precluded nirmatrelvir/ritonavir use, 53% required management, but 56% of these did not have documented advice to hold therapy. This highlights the need to maintain and develop pathways for clinical pharmacology expertise in COVID-19 management.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, azvudine (FNC) / Granlen
Retrospective data, Journal: Comparison of the therapeutic effect of Paxlovid and Azvudine in the treatment of COVID-19: A retrospective study. (Pubmed Central) - Nov 27, 2024
In assessing patient conditions for treatment selection, Paxlovid may be preferable for individuals with renal insufficiency or those exhibiting compromised immune responses. Conversely, for patients experiencing malnutrition or cirrhotic hypoproteinemia, Azvudine could be considered to mitigate the reduction in protein levels.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: Identification and Ranking of Binding Sites from Structural Ensembles: Application to SARS-CoV-2. (Pubmed Central) - Nov 27, 2024
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, serves as a prime example of this, where despite the allocation of substantial resources, Paxlovid is currently the only effective treatment...These results demonstrate the utility of FTMove to rapidly identify actionable sites across a range of targets for a given indication. As such, the approach is expected to be particularly useful for assessing target binding sites for any emerging pathogen, as well as for indications in other disease areas, and providing actionable starting points for structure-based drug design efforts.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Preclinical, Journal: Methylene Blue Has Strong Extracellular Virucidal Activity Against a SARS-CoV-2-Related Pangolin Coronavirus with No Intracellular or In Vivo Efficacy. (Pubmed Central) - Nov 27, 2024
We employed plaque reduction assays and cell infection experiments to compare the extracellular virucidal activity of the compound and its ability to inhibit viral replication in cells to those of nirmatrelvir...Incubation in mouse plasma increased the virucidal EC50 value of methylene blue, indicating that mouse plasma can affect the stability of the compound, although mouse plasma has some extent of natural virucidal activity. These findings elucidate why methylene blue lacks antiviral efficacy in vivo and provide insights for the development of antiviral drugs.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: Integrated Analysis of Remdesivir and Paxlovid in COVID-19 Patients: A Personalized Approach to High-Risk Individuals for Severe Evolution. (Pubmed Central) - Nov 27, 2024
Both drugs can be considered a breakthrough in the current treatment approach to the COVID-19 disease since they provide readily available options that can alleviate the severity of the disease and, hence, the prognosis of patients. That is why their effectiveness relies on the correct administration time and choosing the patient with suitable characteristics regarding the presence of comorbidities and the likelihood of the critical further development of the process.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: The S2 Pocket Governs the Genus-Specific Substrate Selectivity of Coronavirus 3C-Like Protease. (Pubmed Central) - Nov 27, 2024
It is also demonstrated that the S2 pocket is highly correlated with the genus-specific inhibitory potency of PF-07321332 (an FDA-approved drug against COVID-19) on different CoV 3CLpros. This study on 3CLpro provides novel insights to inform evolutionary mechanisms for CoV and develop genera-specific or broad-spectrum drugs against CoVs.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: Clinical Benefits of Sustained Oral Nirmatrelvir/Ritonavir Use for the Outpatient Treatment of COVID-19: Findings from the Taiwanese Health Authority Perspective Using a Decision Tree Modeling Approach. (Pubmed Central) - Nov 26, 2024
In the hypothetical scenario, HCRU increased by 175% compared to the base case, including increases in hospitalizations involving GW, ICU, and MV use (differences: 2067; 623; 591, respectively), bed days (difference: 51,521), symptom days (difference: 51,714), and deaths (difference: 480). Findings indicate that sustained utilization of NMV/r from the THAP reduces the clinical burden of mild-to-moderate COVID-19 through the reduced incidence of COVID-19-related HCRU and deaths.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Biomarker, Retrospective data, Journal: D-dimer for efficacy prediction in COVID-19 patients treated with paxlovid. (Pubmed Central) - Nov 26, 2024
Findings indicate that sustained utilization of NMV/r from the THAP reduces the clinical burden of mild-to-moderate COVID-19 through the reduced incidence of COVID-19-related HCRU and deaths. Our findings suggested that the reduced efficacy of paxlovid could be predicted by elevated D-dimer levels in COVID-19 patients.
- |||||||||| GC376 / Anivive, Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Victrelis (boceprevir) / Roche, Merck (MSD)
Preclinical, Journal: Peptide Aldehydes Incorporating Thiazol-4-yl Alanine Are Potent In Vitro Inhibitors of SARS-CoV-2 Main Protease. (Pubmed Central) - Nov 20, 2024
We synthesized and tested several analogue chimeras of GC376 and boceprevir that have surrogate residues at the P1 and/or P2 position in order to further improve target binding. Both P1 variants with either a nonpolar cyclobutyl or polar thiazol-4-yl alanine resulted in low-micromolar to submicromolar Mpro inhibitors with strong antiviral activity in cell assays.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Clinical, Retrospective data, Review, Journal: SARS-CoV-2 infection rebound among patients receiving antiviral agents, convalescent plasma, or no treatment: a systematic review with meta-analysis. (Pubmed Central) - Nov 19, 2024
Both P1 variants with either a nonpolar cyclobutyl or polar thiazol-4-yl alanine resulted in low-micromolar to submicromolar Mpro inhibitors with strong antiviral activity in cell assays. Virologic rebound of COVID-19 infections appears to be mild and self-limited, and was observed more commonly in nirmatrelvir-ritonavir recipients than in untreated patients, but was also observed in patients treated with molnupiravir or CP.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Xocova (ensitrelvir) / Shionogi, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Journal: SARS-CoV-2 Resistance to Small Molecule Inhibitors. (Pubmed Central) - Nov 19, 2024
This manuscript summarizes mutations in 3CLpro and nsp12, which could potentially reduce the efficacy of drugs. Additionally, it encapsulates recent advancements in small molecule antivirals targeting SARS-CoV-2 viral proteins, including their potential for developing resistance against emerging variants.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: Predictors for COVID-19-Specific and Non-COVID-19-Specific Deaths: A Cohort Study in Taiwan. (Pubmed Central) - Nov 16, 2024
Fully vaccinated individuals (AOR = 0.50; 95% CI [0.33, 0.74]) and Paxlovid recipients (AOR = 0.45; 95% CI [0.20, 0.98]) had lower COVID-19-specific death risks, while comorbid cancer or end-stage renal disease patients faced higher risks of non-COVID-19-specific deaths. Our study findings suggest that vaccination and Paxlovid treatment are crucial for reducing SARS-CoV-2-specific mortalities, while comorbid patients need careful monitoring to reduce non-COVID-19-specific deaths.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, bebtelovimab (LY-CoV1404) / AbCellera, Eli Lilly, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Clinical, Observational data, Journal, Adverse events: Investigating the Safety Profile of Fast-Track COVID-19 Drugs Using the FDA Adverse Event Reporting System Database: A Comparative Observational Study. (Pubmed Central) - Nov 14, 2024
This study demonstrated that real-world data and real-time safety reviews could be effective methods for the timely detection of ADR signals of drugs that have received fast-track approval, as exemplified by COVID-19 drugs. These findings underscore the importance of the continued surveillance, efficient data processing, and establishment of automated pipelines for real-time safety reviews.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Review, Journal: Vitamin D: A key player in COVID-19 immunity and lessons from the pandemic to combat immune-evasive variants. (Pubmed Central) - Nov 13, 2024
Therefore, large-scale randomized trials are required to reach a definitive conclusion. A bibliometric analysis of publications related to vitamin D, immunity, and COVID-19 revealed a significant increase in research activity in this area, particularly in 2020-2024, underscoring the growing recognition of vitamin D's potential role in the context of the pandemic.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Preclinical, Journal: Design and biological evaluation of candidate drugs against zoonotic porcine deltacoronavirus (PDCoV). (Pubmed Central) - Nov 13, 2024
Compound T1, with an isobutyl at the P2 site, displayed improved anti-PDCoV activity in vitro (cell infection model) and in vivo (embryonated chicken egg infection model), and therefore is a potential candidate drug to combat PDCoV. Together, our results identify the substrate-binding mode and substrate specificity of PDCoV 3CLpro, providing insight into the optimization of Nirmatrelvir as an antiviral therapeutic agent against PDCoV.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Journal: Hyphenating sustainability with chemometrics in chromatographic analysis of COVID combo therapy, nirmatrelvir and Molnupiravir, in presence of their overlapping degradation products; blue-green dual evaluation tools. (Pubmed Central) - Nov 13, 2024
Additionally, in order to determine the impact of chemometric methods in minimizing analysis time and reducing solvent, energy, and waste consumption, our chemometric methodology is evaluated in terms of greenness and blueness (dichromic assessment) using AGREE and BAGI, respectively. Besides, the method sustainability using Hexagon was evaluated.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Xocova (ensitrelvir) / Shionogi
Journal: The binding mechanism of failed, in processing and succeed inhibitors target SARS-CoV-2 main protease. (Pubmed Central) - Nov 13, 2024
By gaining insights into the dynamics, we can potentially elucidate why lopinavir/ritonavir, initially considered promising, failed to effectively treat COVID-19. Furthermore, understanding the mechanistic aspects of N3 and NMV inhibition on SCM not only contributes to rational drug discovery against COVID-19 but also aids future studies on the catalytic mechanisms of main proteases in other novel coronaviruses.Communicated by Ramaswamy H. Sarma.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Retrospective data, Journal: Nationwide Target Trial Emulation Evaluating the Clinical Effectiveness of Oral Antivirals for COVID-19 in Korea. (Pubmed Central) - Nov 5, 2024
In conclusion, in this population of CLL and iB-NHL at high risk for poor response to vaccination, the modern management strategy that included PrEP with tixagevimab and cilgavimab and treatment with antiviral drugs resulted in low rates of severe COVID infection and death. Nirmatrelvir/ritonavir and molnupiravir are effective in preventing progression to severe disease in elderly adults with COVID-19.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Cost-Effectiveness Analysis of Paxlovid () - Nov 4, 2024 - Abstract #ISPOREU2024ISPOR_EU_3080;
In conclusion, our study demonstrated an additive interaction between nirmatrelvir-ritonavir and complete vaccination on post-acute outcomes, suggesting greater long-term benefits of the antiviral for fully vaccinated individuals compared to not fully vaccinated patients. Our results suggests that Paxlovid is cost-effective compared to SoC for patients at high risk for severe COVID-19 from a health sector perspective in Portugal.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Requirements to Ensure Patient Safety Through Paxlovid () - Nov 4, 2024 - Abstract #ISPOREU2024ISPOR_EU_255;
This study suggests that utilization of nirmatrelvir/ritonavir is cost-effective compared to SoC for most patient groups, and especially for patients older than 70 years. Paxlovid
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