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  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Review, Journal:  Protein data bank: From two epidemics to the global pandemic to mRNA vaccines and Paxlovid. (Pubmed Central) -  Feb 3, 2025   
    Structure-guided drug discovery by Pfizer, Inc (facilitated by PDB structures), initiated in the 2000s in response to SARS-CoV-1 and resumed in 2020, yielded nirmatrelvir (the active ingredient of Paxlovid) -- a potent, orally-bioavailable inhibitor of the SARS-CoV-2 main protease. You've got to love the Protein Data Bank!
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
    Review, Journal:  The JN.1 variant of COVID-19: immune evasion, transmissibility, and implications for global health. (Pubmed Central) -  Feb 3, 2025   
    It is essential to encourage the public to maintain vaccination and preventive measures to reduce JN.1's impact. Continued research is critical for understanding and managing the evolving landscape of COVID-19 and its emerging variants.
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Journal:  Distal protein-protein interactions contribute to nirmatrelvir resistance. (Pubmed Central) -  Feb 2, 2025   
    Particularly, L50F and other non-active site mutations can enhance the Mpro dimer-dimer interactions and help place the nsp5-6 substrate at the enzyme catalytic center. The structural and enzymatic activity data of Mpro L50F, L50F/E166A/L167F, and others underscore the importance of considering the whole substrate protein in studying Mpro and substrate interactions, and offers important insights into Mpro function, resistance development, and inhibitor design.
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Retrospective data, Journal, Real-world evidence:  Real-world Plasma Exposure of Nirmatrelvir/Ritonavir in Chinese Hospitalized Patients With COVID-19: A Multicenter Retrospective Study. (Pubmed Central) -  Jan 30, 2025   
    The structural and enzymatic activity data of Mpro L50F, L50F/E166A/L167F, and others underscore the importance of considering the whole substrate protein in studying Mpro and substrate interactions, and offers important insights into Mpro function, resistance development, and inhibitor design. Nirmatrelvir Ctrough was high in Chinese patients with COVID-19, and therapeutic drug monitoring should not be routinely recommended, except in patients with renal impairment.
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Journal:  Small-molecule inhibition of SARS-CoV-2 NSP14 RNA cap methyltransferase. (Pubmed Central) -  Jan 29, 2025   
    TDI-015051 also inhibited viral replication in primary small airway epithelial cells and in a transgenic mouse model of SARS CoV-2 infection with an efficacy comparable with the FDA-approved reversible covalent protease inhibitor nirmatrelvir6. The inhibition of viral cap methylases as an antiviral strategy is also adaptable to other pandemic viruses.
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Journal:  Applications of Machine Learning Approaches for the Discovery of SARS-CoV-2 PLpro Inhibitors. (Pubmed Central) -  Jan 17, 2025   
    While Pfizer introduced Paxlovid, an FDA-approved antiviral targeting the SARS-CoV-2 main protease (Mpro), this study focuses on designing new antivirals against another protease, papain-like protease (PLpro), which is crucial for viral replication and immune suppression...Additionally, the hit-to-lead optimization of chemotype 7 produced 10 more analogs. These PLpro inhibitors provide promising templates for antiviral development against COVID-19.
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Journal:  An Investigation of Nirmatrelvir (Paxlovid) Resistance in SARS-CoV-2 Mpro. (Pubmed Central) -  Dec 23, 2024   
    We also analyzed three of the most common SARS-CoV-2 Mpro mutations that have been seen in patients recently, and only a measured increase in nirmatrelvir resistance was seen when the more recently appearing A285V is added to both P132H and K90R. Taken together, our results predict that resistance to nirmatrelvir will be slower to develop than expected based on experience with other viral protease inhibitors, perhaps due in part to the close structural correspondence between nirmatrelvir and SARS-CoV-2 Mpro's preferred substrates.
  • ||||||||||  Evusheld (cilgavimab/tixagevimab) / AstraZeneca, Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Journal:  Acute kidney injury and tacrolimus toxicity in a kidney transplant recipient treated with nirmaltrevir/ritonavir: a case report. (Pubmed Central) -  Dec 21, 2024   
    This acute kidney injury was attributed to tacrolimus toxicity resulting from a drug-drug interaction with Paxlovid. While transplant recipients have an increased risk of severe disease, current Australian guidelines recommend against Paxlovid use in adults taking medications that are heavily dependent on CYP3A4 for clearance, including calcineurin and mammalian target of rapamycin inhibitors.
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
    Journal, HEOR:  Impact of oral early antiviral therapies for mild-moderate COVID-19 in the outpatient's setting during Omicron era: a pharmacoeconomic analysis. (Pubmed Central) -  Dec 19, 2024   
    In the context of the Omicron variant during the COVID-19 pandemic, the use of early oral antiviral agents in vaccinated individuals was found to be more expensive compared to avoid treatment, primarily due to the high costs associated with it. To enhance the efficiency in resource allocation, it is essential to pursue policies aimed at reducing drug costs, along with conducting further pharmaco-economic studies.
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Journal:  Nirmatrelvir/ritonavir treatment and risk for post-acute sequelae of COVID-19 in older Singaporeans. (Pubmed Central) -  Dec 18, 2024   
    The beneficial effect of N/r treatment in reducing progression is more pronounced in unvaccinated patients. Early outpatient receipt of nirmatrelvir/ritonavir did not significantly reduce risk of postacute cardiovascular, neurological, respiratory, and autoimmune sequelae or the risk of postacute symptoms in a boosted cohort of older Singaporeans.
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Journal:  Acquired Aquagenic Syringeal Keratoderma Following COVID-19 Infection. (Pubmed Central) -  Dec 17, 2024   
    A 24-year-old atopic male presented with a 2-week subacute history of bilateral palmar edema with whitish-colored papules after exposure to water, 3 months after having had COVID-19 infection treated with a full course of ritonavir-boosted nirmatrelvir (PAXLOVIDTM)...Our patient may have had a predisposition to recurrent ASK due to his history of atopy including atopic dermatitis and food allergy anaphylaxis combined with prior COVID-19 infection. It is possible that ASK is a novel manifestation of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC) infection or long COVID.
  • ||||||||||  warfarin / Generic mfg.
    Journal, Real-world evidence, Real-world:  Interactions of warfarin with COVID-19 vaccine/drugs, monoclonal antibodies, and targeted anticancer agents from real-world data mining. (Pubmed Central) -  Dec 16, 2024   
    Remdesivir combined with warfarin was associated with a statistically significant increase in bleeding events (P = 0.047); while the risk was not significant after adjusting for age and sex (aOR: 1.79; P = 0.2)...This study provides real-world evidence of newly identified drug interactions with warfarin. It reminds clinicians to monitor INR and adjust warfarin doses accordingly when used in combination with these medications.
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Journal:  A Complex Case of COVID-19 Pneumonitis in a Patient With Follicular Lymphoma. (Pubmed Central) -  Dec 16, 2024   
    A multidisciplinary involvement altered treatment to include a combination of antivirals nirmatrelvir/ritonavir (Paxlovid) and remdesivir, a monoclonal antibody and immunoglobulins leading to a clinical cure. This report highlights the need for a more tailored approach in this patient sub-group than the rest of the population.
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    New trial:  Saliva PCR in Pregnant Women with COVID-19 (clinicaltrials.gov) -  Dec 16, 2024   
    P=N/A,  N=37, Completed, 
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Trial completion date, Trial primary completion date:  CanTreatCOVID: Canadian Adaptive Platform Trial of Treatments for COVID-19 in Community Settings (clinicaltrials.gov) -  Dec 13, 2024   
    P3,  N=10000, Recruiting, 
    This report highlights the need for a more tailored approach in this patient sub-group than the rest of the population. Trial completion date: Jan 2025 --> Mar 2026 | Trial primary completion date: Jan 2024 --> Mar 2026
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Journal:  A theory for viral rebound after antiviral treatment: A study case for SARS-CoV-2. (Pubmed Central) -  Dec 11, 2024   
    A fraction of individuals infected with SARS-CoV-2 experienced rebounds when treated with effective antivirals such as Nirmatrelvir/Ritonavir (Paxlovid)...Without relying on the effects of the adaptive immune system or the resistance through viral mutations, we develop mathematical conditions for antiviral treatments to avoid viral rebound. Simulation results illustrate the critical role of dosage (i.e., the doses and timing of administration) in taking advantage of highly effective drugs and tailoring therapies.
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Journal:  Mitigating Paxlovid (Pubmed Central) -  Dec 11, 2024   
    In this study, the skin permeability potential of Nirmatrelvir was assessed using various in silico models. The prediction results suggest that Nirmatrelvir could be administrated via the transdermal route, offering a promising avenue to enhance the efficacy of anti-COVID-19 agents.
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Xocova (ensitrelvir) / Shionogi
    Journal:  Biological Characterization of AB-343, a Novel and Potent SARS-CoV-2 Mpro Inhibitor with Pan-Coronavirus Activity. (Pubmed Central) -  Dec 10, 2024   
    No change in AB-343 potency was observed against Mpro of SARS-CoV-2 variants of concern, including Omicron, suggesting that AB-343 could be developed as a treatment against currently circulating coronaviruses. AB-343 also remained active against several Mpro variants which confer significant resistance to nirmatrelvir and ensitrelvir, which are presently the only Mpro inhibitors authorized for the treatment of COVID-19, further supporting the evaluation of AB-343 as a novel and potent therapeutic for COVID-19 and other coronaviruses.
  • ||||||||||  remdesivir / Generic mfg., Paxlovid (nirmatrelvir/ritonavir) / Pfizer, thapsigargin / University of Nottingham, Pirbright Institute
    Journal:  X-206 exhibits broad-spectrum anti-?-coronavirus activity, covering SARS-CoV-2 variants and drug-resistant isolates. (Pubmed Central) -  Dec 10, 2024   
    X-206 exhibited antiviral activity against nirmatrelvir- and remdesivir-resistant SARS-CoV-2 isolates and SARS-CoV-2 variants, including Delta, BA.5, and XBB.1. Consequently, the mechanism of action of these compounds with anti-?-coronavirus activities may differ from that of the approved direct-acting drugs for SARS-CoV-2, thereby offering potential use as a cocktail with other antivirals, and serving as a chemical basis for developing therapeutic agents against ?-coronaviruses in preparation for the next spillover and pandemic.
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Observational data, Retrospective data, Journal:  Impact of Paxlovid on Tacrolimus Concentration in Kidney Transplant Patients: A Retrospective Observational Study. (Pubmed Central) -  Dec 8, 2024   
    In summary, this is the first study to indicate a significant influence of paxlovid on tacrolimus levels in Chinese patients undergoing kidney transplantation. During paxlovid treatment, careful observation and tailored tacrolimus management are crucial to guarantee safe administration and circumvent negative consequences.
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Journal:  Paxlovid Awareness, Reporting Bias: The Authors Reply. (Pubmed Central) -  Dec 3, 2024   
    Nirmatrelvir/ritonavir use within five days reduced the time to viral clearance (HR=1.51, 95% CI 1.01-2.23).ConclusionsNirmatrelvir/ritonavir use within five days in hospitalized HM patients with mild-to-moderate COVID-19 does not reduce mortality but shortens infection duration. No abstract available
  • ||||||||||  Paxlovid (nirmatrelvir/ritonavir) / Pfizer
    Journal:  Paxlovid Awareness, Reporting Bias. (Pubmed Central) -  Dec 3, 2024   
    No abstract available No abstract available