- |||||||||| Phase classification, Enrollment change, Trial completion date, Trial primary completion date: RECOVERY: Randomised Evaluation of COVID-19 Therapy (clinicaltrials.gov) - Jan 5, 2024
P3, N=70000, Recruiting,
Phase classification: P2/3 --> P3 | N=50000 --> 70000 | Trial completion date: Nov 2032 --> Jun 2036 | Trial primary completion date: Nov 2023 --> Jun 2026
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Xocova (ensitrelvir) / Shionogi
Journal: A naturally occurring G11S mutation in the 3C-like protease from the SARS-CoV-2 virus dramatically weakens the dimer interface. (Pubmed Central) - Dec 28, 2023
We have used concentration-dependent activity assays and mass spectrometry to show that indeed the G11S mutation reduces the stability of the dimer by 600-fold. This helps to set a quantitative benchmark for the minimum potency required of any future protein-protein interaction inhibitors targeting 3CL and raises interesting questions regarding how coronaviruses bearing such weakly dimerizing 3CL enzymes are capable of replication.
- |||||||||| Preclinical, Journal: Existence of Quantum Pharmacology in Sartans: Evidence in Isolated Rabbit Iliac Arteries. (Pubmed Central) - Dec 27, 2023
The ability of ARBs to inhibit contraction responses even at ultra-low concentrations provides evidence of the existence of quantum pharmacology. Furthermore, the ability of ACC519T and BV6(K) to modulate blood pressure and ACE2 activity, respectively, indicates their therapeutic potential against hypertension.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: Nirmatrelvir/ritonavir drug-drug interactions in primary care outpatients (Pubmed Central) - Dec 26, 2023
Compared to standard treatment, Paxlovid significantly reduced nucleic acid shedding time, days until negative swab test, and days of first symptoms resolution, as well as improved nucleic acid test negative rate and post-COVID-19 condition. Our search of potential drug interactions and subsequent dose adjustments and modifications of the patient's usual treatment has helped avoid potential toxicities ensuring a safe use of nirmatrelvir/ritonavir.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Journal: SARS-CoV-2 Rebound With and Without Use of COVID-19 Oral Antivirals. (Pubmed Central) - Dec 25, 2023
Persons receiving antiviral treatment might be at higher risk for rebound compared with persons not receiving treatment because of host factors or treatment-induced viral suppression early in the course of illness. The potential for rebound should not deter clinicians from prescribing lifesaving antiviral treatments when indicated to prevent morbidity and mortality from COVID-19.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Review, Journal: Disparate viral pandemics from COVID19 to monkeypox and beyond: a simple, effective and universal therapeutic approach hiding in plain sight. (Pubmed Central) - Dec 22, 2023
The Pfizer drug paxlovid which is composed of nirmatrelvir, a peptidomimetic protease inhibitor of SARS-CoV2 Mpro enzyme, and ritonavir to retard degradation of nirmatrelvir, is the current FDA recommended treatment of early COVID19...We developed a peptidomimetic antagonist, based on JAK2 activation loop, against SOCS1/3 and showed that it synergizes with the IFN mimetics for potent broad spectrum antiviral activity without the toxicity of intact IFN molecules. IFN mimetics and the SOCS1/3 antagonist should have an advantage over currently used antivirals in terms of safety and potency against a broad spectrum of viruses.
- |||||||||| Journal: Effectiveness of Vaccines and Antiviral Drugs in Preventing Severe and Fatal COVID-19, Hong Kong. (Pubmed Central) - Dec 22, 2023
We compared the effectiveness and interactions of molnupiravir and nirmatrelvir/ritonavir and 2 vaccines, CoronaVac and Comirnaty, in a large population of inpatients with COVID-19 in Hong Kong...Among patients >80 years of age, 3-4 doses of Comirnaty vaccine were associated with significantly lower risks for target outcomes. Policies should encourage COVID-19 vaccination, and oral antivirals should be made accessible to infected persons within 5 days of confirmed diagnosis.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: Optimal timing of nirmatrelvir/ritonavir treatment after COVID-19 symptom onset or diagnosis: target trial emulation. (Pubmed Central) - Dec 21, 2023
Here we show that, by emulating a randomized target trial using real-world electronic medical record data from all 87,070 adult users of nirmatrelvir/ritonavir in Hong Kong between 16th March 2022 and 15th January 2023, early initiation of nirmatrelvir/ritonavir treatment (0 to 1 days after symptom onset or diagnosis) significantly reduced the incidence of 28-day all-cause mortality and hospitalization compared to delayed initiation (2 or more days) (absolute risk reduction [ARR]: 1.50% (95% confidence interval 1.17-1.80%); relative risk [RR]: 0.77 (0.73, 0.82)), but may be associated with a significant elevated risk of viral burden rebound (ARR: -1.08% (-1.55%, -0.46%)), although the latter estimates were associated with high uncertainty due to limited sample sizes. As such, patients should continue to initiate nirmatrelvir/ritonavir early after symptom onset or diagnosis to better protect against the more serious outcomes of hospitalization and mortality.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Enrollment open: Pharmacist Management of Paxlovid eVisits (clinicaltrials.gov) - Dec 20, 2023
P=N/A, N=1560, Recruiting,
Our results highlight the importance of early utilization and/or NR indication, which may yield clinical advantages for patients with RD infected with SARS-CoV-2. Not yet recruiting --> Recruiting
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Xevudy (sotrovimab) / GSK, National Institutes of Health, Vir Biotech, National Institute of Allergy and Infectious Diseases
Journal, Combination therapy: Optimizing COVID-19 treatment in immunocompromised patients: early combination therapy with remdesivir, nirmatrelvir/ritonavir and sotrovimab. (Pubmed Central) - Dec 20, 2023
The combination of antiviral and sotrovimab in the early phase of COVID-19 is well tolerated by immunocompromised patients and is associated with 100% of virological clearance. Patients treated later have lower response rates and higher disease severity, but whether therapy plays a causative role in such findings has yet to be determined.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Biomarker, Journal, Metastases: Prognostic Factors and Outcomes in Advanced Stage Lung Cancer Patients with COVID-19 Omicron Variant Infection. (Pubmed Central) - Dec 20, 2023
Treatment included Paxlovid, prednisolone, anticoagulation, and ventilation...Lower oxygen saturation, decreased lymphocyte/neutrophil ratio on day 7, and diffuse lung lesions on CT scans were associated with worse outcomes. Clinicians should prioritize timely and comprehensive management to improve survival rates in this population.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Review, Journal: Covalent-reversible peptide-based protease inhibitors. Design, synthesis, and clinical success stories. (Pubmed Central) - Dec 18, 2023
Covalent-reversible inhibitors can hipothetically provide the safety of the reversible modifiers combined with the high potency and specificity of their irreversible counterparts. Herein, we will present the main groups of covalent-reversible peptide-based inhibitors, focusing on their design, synthesis, and successful drug development programs.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Enrollment closed, Enrollment change: ESOA-19: Effectiveness and Safety of New Oral Antivirals for COVID-19 (clinicaltrials.gov) - Dec 18, 2023
P=N/A, N=211, Active, not recruiting,
Herein, we will present the main groups of covalent-reversible peptide-based inhibitors, focusing on their design, synthesis, and successful drug development programs. Recruiting --> Active, not recruiting | N=69 --> 211
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: Transplacental passage of nirmatrelvir in pregnant women with COVID-19. (Pubmed Central) - Dec 17, 2023
In conclusion, our results from the in vitro characterization of pomotrelvir antiviral activity support its further clinical development as an alternative COVID-19 therapeutic option. No abstract available
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: COVID-19 and pregnancy: interrelationships with asthma and allergy. (Pubmed Central) - Dec 17, 2023
Although overall risks are low, pregnant people who get infected with COVID-19 are at higher risk for maternal and pregnancy complications. Antiviral treatment is available for pregnant people with mild to moderate symptoms of COVID-19 with reassuring safety data to date, and dexamethasone is the mainstay of inpatient therapy.
- |||||||||| Comirnaty (tozinameran) / Pfizer, Fosun Pharma, BioNTech, Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: The course of patients with hairy cell leukemia during the omicron surge of the Covid-19 pandemic. (Pubmed Central) - Dec 17, 2023
Humoral immune response after three doses of the BNT162b2 mRNA vaccination regimen was evaluated in 40 patients and was attained in 67.5%. Based on multivariate analysis: unfavorable outcome was significantly more common in patients with HCL above 65
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: Surveillance and Outcomes of Pediatric Hematopoietic Stem Cell Transplantation Recipients During the Recent COVID-19 Outbreak in China. (Pubmed Central) - Dec 13, 2023
Various treatments were employed hospitalized patients, including Paxlovid (n=19, 55.9%), methylprednisolone (n=7, 20.6%), IL-6 antibody (n=2, 5.9%), mesenchymal stem cells (n=3, 8.8%), and exosomes nebulization therapy (n=2, 5.9%)...This study provides insights into clinical features, therapeutic measures, and outcomes of pediatric HSCT recipients following COVID-19 infection in a large HSCT center in China. These findings contribute to our understanding of COVID-19 in this population and inform strategies to mitigate the impact the pandemic's impact on their care.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: Applications of peptide-functionalized or unfunctionalized selenium nanoparticles for the passivation of SARS-CoV-2 variants and the respiratory syncytial virus (RSV). (Pubmed Central) - Dec 7, 2023
Moreover, it has been well documented that when patients stop taking some commercial therapies (such as Paxlovid), COVID from these variants may return and may even be more contagious...The peptides showed good gastro-intestinal (GI) tract absorption and bioavailability as predicted using the partition coefficient (QP logP), and high-water solubility as detected by QPlogS. According to these promising results, functionalizing biogenic Se nanoparticles with these novel peptides should be further studied in vivo for the improved diagnosis, prevention, and treatment of SARS-CoV-2, RSV, and other respiratory virus infections.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Journal: Nirmatrelvir and Molnupiravir and Post-COVID-19 Condition in Older Patients. (Pubmed Central) - Dec 5, 2023
According to these promising results, functionalizing biogenic Se nanoparticles with these novel peptides should be further studied in vivo for the improved diagnosis, prevention, and treatment of SARS-CoV-2, RSV, and other respiratory virus infections. No abstract available
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: In silico studies of anti-oxidative and hot temperament-based phytochemicals as natural inhibitors of SARS-CoV-2 Mpro. (Pubmed Central) - Dec 4, 2023
The computational results suggested high binding affinities of savinin, betulinic acid and curcumin to both the monomeric and dimeric deposited states of Mpro, while highlighting the lower binding energy of betulinic acid in comparison with savinin and curcumin and even Nirmatrelvir, leading to a greater stability of the betulinic acid-SARS-CoV-2 Mpro complex. Overall, based on the increasing mutation rate in the spike protein and the fact that the SARS-CoV-2 Mpro remains highly conserved, this study provides an insight into the use of phytochemicals against COVID-19 and other coronavirus diseases.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Journal: Long COVID and possible preventive options. (Pubmed Central) - Dec 4, 2023
Finally, recently, several clinical trials are in progress with either dietary supplements or drugs with different mechanisms of action. Additional information on the precise mechanisms, risk factors of Long COVID may result in successful preventive and therapeutic management of Long Covid 19 syndrome.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Review, Journal: Nirmatrelvir combined with ritonavir for preventing and treating COVID-19. (Pubmed Central) - Nov 30, 2023
There is no available evidence supporting the use of nirmatrelvir/ritonavir for preventing SARS-CoV-2 infection. We are continually updating our search and making search results available on the OSF platform.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Preclinical, Journal: Antiviral peptides inhibiting the main protease of SARS-CoV-2 investigated by computational screening and in vitro protease assay. (Pubmed Central) - Nov 30, 2023
While a small-molecule drug (Paxlovid) received emergency approval, small-molecule drugs have low target specificity and higher toxicity...The solution-state nuclear magnetic resonance (NMR) structure of temporin L was determined in the absence of sodium dodecyl sulfate (SDS) micelles and was compared to previous temporin structures. This combined investigation provides critical insights and assists us to further develop peptide inhibitors of SARS-CoV-2 Mpro through structural guided investigation.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Trial completion date, Trial primary completion date: A Study to Learn About the Medicine (PF-07321332 or Nirmatrelvir/Ritonavir) in Healthy Lactating Women (clinicaltrials.gov) - Nov 30, 2023
P1, N=8, Recruiting,
This combined investigation provides critical insights and assists us to further develop peptide inhibitors of SARS-CoV-2 Mpro through structural guided investigation. Trial completion date: Sep 2023 --> Dec 2023 | Trial primary completion date: Sep 2023 --> Dec 2023
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Journal: Vaccination and Antiviral Treatment Reduce the Time to Negative SARS-CoV-2 Swab: A Real-Life Study. (Pubmed Central) - Nov 29, 2023
Further, in the elderly patients under study, previous vaccination and antiviral treatment synergize to reduce time to negativity. This translates into a shorter hospitalization time and a lower risk of transmission through patients and connected healthcare workers in a hospital ward setting, with considerable improvement in cost-effective care management.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer
Journal: Risk of acute liver injury following the nirmatrelvir/ritonavir use. (Pubmed Central) - Nov 29, 2023
The risk of ALI associated with nirmatrelvir/ritonavir treatment for COVID-19 was elevated in the pre-exposure period, but not following nirmatrelvir/ritonavir initiation. ALI following nirmatrelvir/ritonavir treatment were mostly mild and less severe than ALI events in non-nirmatrelvir/ritonavir users.
- |||||||||| Paxlovid (nirmatrelvir/ritonavir) / Pfizer, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD), Xevudy (sotrovimab) / GSK, National Institutes of Health, Vir Biotech, National Institute of Allergy and Infectious Diseases
Review, Journal, HEOR: The impact of vaccination and outpatient treatment on the economic burden of covid-19 in the United States omicron era: a systematic literature review. (Pubmed Central) - Nov 28, 2023
Despite evidence gaps, findings from the SLR highlight the significant positive impact that vaccination and outpatient treatment have had on HCRU in the US, including periods of Omicron predominance. Continued research is needed to inform clinical and policy decision-making in the US as COVID-19 continues to evolve as an endemic disease.
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