Paxlovid (nirmatrelvir/ritonavir) / Pfizer, China Meheco Group - LARVOL DELTA

Discovery of broad-spectrum antivirals targeting viral proteases using in silico structural modeling and cellular analysis. (PubMed, Antiviral Res) - "As predicted, NIP-22c and CIP-1 showed broad-spectrum antiviral activity with EC50 values in the nanomolar range against SARS-CoV-2, norovirus, enterovirus and rhinovirus by targeting 3CL/3Cpro. In contrast, nirmatrelvir did not show activity up to 10 μM against all three viruses and the mechanism of inactivity of nirmatrelvir was hypothesized through binding pocket analysis using molecular dynamics simulations."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CDKN1A

The protease inhibitor Nirmatrelvir synergizes with inhibitors of GRP78 to suppress SARS-CoV-2 replication. (PubMed, Antiviral Res) - "In a hamster model of COVID-19, the combination of Nirmatrelvir with HA15 alleviated pneumonia-induced pulmonary atelectasis more effectively than the single drugs. In conclusion, inhibition of the virus Main protease and cellular GRP78 cooperatively diminishes virus replication and may improve COVID-19 therapy."

Journal • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • HSPA5 • SPECC1

Visualization of FDA Adverse Drug Reaction Reports: Development and Usability Study of the VisDrugs Web Server. (PubMed, JMIR Form Res) - "Using Paxlovid (COVID-19 treatment) and hydroxychloroquine (anti-malaria drug) as case studies, we benchmarked VisDrugs using reports for Paxlovid (n=16,708) and hydroxychloroquine (n=6150). The platform's demographic analysis features add insights into ADR variations by age and gender, supporting drug safety research. In the future, the website will include more subgroup or condition filtering options, offering personalized ADR analysis and comparison features to meet the diverse research needs of users."

Adverse drug reaction • Journal • Cardiomyopathy • Cardiovascular • Infectious Disease • Malaria • Novel Coronavirus Disease • Retinal Disorders

Multitarget-based in silico screening from phytoactive compounds of Garcinia linii fighting toward severe acute respiratory syndrome coronavirus-2. (PubMed, Tzu Chi Med J) - "Papain-like protease, main protease, RNA-dependent RNA polymerase, endoribonuclease (nsp15), receptor-binding domain-angiotensin-converting enzyme 2, transmembrane serine protease 2 (TMPRSS2), and 2'- O-ribose methyltransferase (2'MTase), which were subjected to an unbiased in silico screening against 22 small molecules originating from Garcinia linii concomitantly with Remdesivir, Nirmatrelvir, and Molnupiravir were approved by Food and Drug Administration as repurposing drugs against SARS-CoV-2 invasion. The in silico results showed that natural bioactive compounds containing α-Tocopheryolquinone, 6β-Hydroxystigmast-4-en-3-one, Squalene, Rutin and Quercetin have a high binding affinity with seven selected viral protein targets concurrently with the preference of absorption, distribution, metabolism, excretion, and toxicity and drug-likeness. This study provides potential phytoactive compounds from G. linii through multi-target screen with molecular dynamic..."

Journal • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Top 20 Research Studies of 2024 for Primary Care Physicians. (PubMed, Am Fam Physician) - "Based on a network meta-analysis, the oral antibiotics most likely to be effective for community-acquired pneumonia are telithromycin (not available in the United States), azithromycin, amoxicillin-clavulanate, and the quinolones levofloxacin and nemonoxacin (not available in the United States). The oral antivirals molnupiravir and nirmatrelvir-ritonavir reduce hospitalizations in immunocompromised patients with COVID-19. In average-risk infants, a single dose of nirsevimab reduces hospitalizations due to respiratory syncytial virus...Low-dose amitriptyline is effective as second-line therapy for irritable bowel syndrome...Phentermine-topiramate and GLP-1 receptor agonists are the most effective drugs for promoting weight loss...For patients who do not quit smoking after a trial of varenicline or combined nicotine replacement therapy, a higher dose of either drug can increase quit rates...Oral naltrexone and acamprosate are safe and effective treatments for alcohol use..."

Journal • Review • Addiction (Opioid and Alcohol) • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Congestive Heart Failure • Diabetes • Fatigue • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Heart Failure • Infectious Disease • Metabolic Disorders • Myocardial Infarction • Nephrology • Novel Coronavirus Disease • Obesity • Otorhinolaryngology • Pneumonia • Respiratory Diseases • Respiratory Syncytial Virus Infections • Sinusitis • Type 2 Diabetes Mellitus

Carboxylesterase Factors Influencing the Therapeutic Activity of Common Antiviral Medications Used for SARS-CoV-2 Infection. (PubMed, Pharmaceutics) - "Several small-molecule antiviral drugs, including molnupiravir, favipiravir, remdesivir, and nirmatrelvir have been shown to inhibit SARS-CoV-2 replication and are approved for treating SARS-CoV-2 infections. In this review, we examine how CES-related cellular and genetic factors influence the therapeutic activities of these widely used COVID-19 medications. This article highlights implications for improving product design, targeted inhibition, and personalized medicine by exploring genetic variations and their impact on drug metabolism and efficacy."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Associations Between Antiprotozoal Treatments and Reduced Mortality Across Populations Suggest That Protozoal Colonization May Contribute Significantly to Human Mortality and Age-Related Morbidity. (PubMed, medRxiv) - "This screen identified two antiprotozoal agents, atovaquone-proguanil and mefloquine, as strongly associated with increased longevity (odds ratios for 10-year mortality: 0.43 and 0.32; FDR = 0.0002 and 0.0001, respectively). We validated these associations in the U.S.-based TriNetX federated network, confirming that these two antiprotozoals, along with nirmatrelvir-ritonavir-a medication used to prevent severe COVID-19 outcomes and possessing antiprotozoal properties-were associated with significantly reduced mortality and a lower incidence of major age-related conditions, including diabetes mellitus, cardiovascular and cerebrovascular diseases, renal insufficiency, dementia, pulmonary disease, liver disease, and malignancies...Taken together, these findings suggest that elimination of protozoal parasites-notably Toxoplasma gondii - may significantly reduce human age-related morbidity and mortality while increasing the risk of specific auditory, ophthalmic, and..."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Dementia • Dermatology • Dermatopathology • Diabetes • Hepatology • Immunology • Infectious Disease • Lichen Planus • Metabolic Disorders • Nephrology • Novel Coronavirus Disease • Oncology • Ophthalmology • Otorhinolaryngology • Pulmonary Disease • Renal Disease • Respiratory Diseases • Sjogren's Syndrome • Vascular Neurology

COVID-19 Infection during Pregnancy in Transplant Recipients (WTC 2025) - "Immunosuppression consisted of tacrolimus 38, belatacept 3, azathioprine 28, and prednisone 18...Treatment for COVID-19 infection was monoclonal antibodies in 11, nirmatrelvir/ritonavir in 2 and remdesivir in 1; supportive care was provided in 27 cases... Pregnant transplant recipients have reported COVID-19 infection, most commonly during the second trimester. To date recipients have not reported any graft loss related to COVID-19 post-pregnancy. Additionally, no sequelae of in utero COVID-19 exposure or anti-COVID-19 treatment have been noted in the children."

Clinical • Cardiovascular • Diabetes • Gestational Diabetes • Gynecology • Hypertension • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Transplantation

Home Infusion Short Course Remdesivir for Solid Organ Transplant Patients with COVID-19 (WTC 2025) - "The recommended oral antiviral, nirmatrelvir/ritonavir has significant drug-drug interactions, including with tacrolimus. Patients receiving home infusion remdesivir had low hospitalization and mortality rates, suggesting reduced risk of disease progression. Additionally, this program has netted a cost savings of $634000 by avoiding hospitalization for administration of remdesivir. Home infusion of remdesivir is an innovative delivery method and may reduce overall cost of healthcare."

Clinical • Infectious Disease • Novel Coronavirus Disease • Solid Organ Transplantation • Transplantation

A Study to Understand How the Use of Paxlovid Affected Healthcare Use in People With Pre-existing Conditions. (clinicaltrials.gov) - P=N/A | N=14000 | Completed | Sponsor: Pfizer

HEOR • New trial • Infectious Disease • Novel Coronavirus Disease

A Study to Learn About the Study Medicine (Nirmatrelvir Plus Ritonavir) in Pregnant Women With COVID-19 (clinicaltrials.gov) - P1 | N=25 | Terminated | Sponsor: Pfizer | Active, not recruiting ➔ Terminated; The trial prematurely terminated due to the inability to recruit the planned number of subjects. The decision to terminate the trial was not based on any safety concerns.

Trial termination • Infectious Disease • Novel Coronavirus Disease

Targeting SARS-CoV-2 main protease: a pharmacophore and molecular modeling approach. (PubMed, J Mol Model) - "Molecular docking against four co-crystal structures of the inhibitor/Mpro complex, followed by molecular dynamics (MD) simulations and binding free energy calculations, identified E912-0363 and G740-1003 as promising candidates with binding affinities comparable to nirmatrelvir...Binding free energy calculations were performed using the MM/GBSA method. Extended 500-ns MD simulations were carried out for the most promising candidate, E912-0363, to evaluate its long-term stability and interaction with the Mpro binding site."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

SARS-CoV-2 rebound and post-acute mortality and hospitalization among patients admitted with COVID-19: cohort study. (PubMed, Nat Commun) - "A similar increase in the risk of post-acute mortality is also observed in nirmatrelvir/ritonavir-treated patients (HR, 1.78; 95% CI, 1.41-2.25; RD, 12.55%) and molnupiravir-treated patients (HR, 1.47; 95% CI, 1.18-1.82; RD, 4.90%). The virologic rebound may thus serve as an early marker for post-COVID-19 condition, enabling healthcare officials to monitor and provide timely intervention for long COVID."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Nirmatrelvir-ritonavir versus placebo-ritonavir in individuals with long COVID in the USA (PAX LC): a double-blind, randomised, placebo-controlled, phase 2, decentralised trial. (PubMed, Lancet Infect Dis) - P2 | "Nirmatrelvir-ritonavir administered for 15 days did not significantly improve health outcomes in participants with long COVID compared with placebo-ritonavir at day 28. However, the study showed the feasibility of large-scale, decentralised trials in long COVID."

Journal • P2 data • Hepatology • Infectious Disease • Nephrology • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases • CYP3A4

A Study to Learn About the Study Medicine Paxlovid (Nirmatrelvir + Ritonavir) in Adults Aged 60 and Older Living in Korean Long-term Care Hospitals Who Have COVID-19 (clinicaltrials.gov) - P=N/A | N=1200 | Not yet recruiting | Sponsor: Pfizer

New trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Potential Glucose-Lowering Properties of Paxlovid® in Type 2 Diabetes Patients (ENDO 2025) - "This drug has been shown to alter blood glucose levels in patients with diabetes by interfering with common antidiabetic agents such as metformin and insulin to raise blood glucose levels... It is widely understood that bacterial and viral infectious agents may transiently raise blood glucose levels during the active infection phase. Additionally, those with Type 2 diabetes are markedly more likely to develop severe viral infections because hyperglycemia may impair immune function. Prior studies have indicated that SARS-CoV-2 infection and Paxlovid® treatment may raise blood glucose levels, not lower them."

Clinical • Diabetes • Endocrine Disorders • Hypoglycemia • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases • Type 2 Diabetes Mellitus

Potential Glucose-Lowering Properties of Paxlovid® in Type 2 Diabetes Patients (ENDO 2025) - "This drug has been shown to alter blood glucose levels in patients with diabetes by interfering with common antidiabetic agents such as metformin and insulin to raise blood glucose levels... It is widely understood that bacterial and viral infectious agents may transiently raise blood glucose levels during the active infection phase. Additionally, those with Type 2 diabetes are markedly more likely to develop severe viral infections because hyperglycemia may impair immune function. Prior studies have indicated that SARS-CoV-2 infection and Paxlovid® treatment may raise blood glucose levels, not lower them."

Clinical • Diabetes • Endocrine Disorders • Hypoglycemia • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases • Type 2 Diabetes Mellitus

A Study to Learn About Effects of Living With COVID-19 and the Use of the Medicines Nirmatrelvir-Ritonavir in Treating COVID-19. (clinicaltrials.gov) - P=N/A | N=1 | Recruiting | Sponsor: Pfizer | Trial completion date: Aug 2024 ➔ Dec 2025 | Trial primary completion date: Aug 2024 ➔ Dec 2025

HEOR • Real-world evidence • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Evaluation of a Protocol Managing the Cyclosporine and Nirmatrelvir/Ritonavir Interaction in Kidney Transplant Recipients. (PubMed, Kidney360) - "Though cyclosporine levels outside therapeutic range were common immediately after completion of nirmatrelvir/ritonavir treatment, levels were restored rapidly. No clinically relevant safety events occurred within the 30-days. Adherence to the protocol is crucial when using nirmatrelvir/ritonavir in kidney transplant recipients."

Journal • Acute Kidney Injury • Infectious Disease • Nephrology • Novel Coronavirus Disease • Transplant Rejection • Transplantation

Economic evaluation of oral nirmatrelvir/ritonavir versus best supportive care in patients at high risk for progression to severe COVID-19 in Germany: a cost-effectiveness analysis. (PubMed, J Med Econ) - "Contemporary data is essential to ensure the model inputs and the outcomes remain relevant as there may be changes in natural disease course or effectiveness of NMV/r.ConclusionsThis cost-effectiveness analysis of NMV/r treatment from a German healthcare payer perspective demonstrates how by preventing progression to severe COVID-19, NMV/r reduces healthcare resource use, associated costs and preserves LY of patients. This analysis provides crucial economic rationale for decision making by policy makers."

HEOR • Journal • Critical care • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Effectiveness of nirmatrelvir/ritonavir and molnupiravir against long COVID in patients with chronic liver disease: cohort study (IDDF 2025) - "Molnupiravir was significantly associated with a lower risk of post-acute mortality (HR, 0·70 [95% CI, 0·56 to 0·87]; p=0·0015) and hospitalization due to ARDS, compared to no antiviral treatment.Download figure Open in new tab Download powerpoint Abstract IDDF2025-ABS-0094 Figure 1 Flowcharts of patient inclusion and exclusionDownload figure Open in new tab Download powerpoint Abstract IDDF2025-ABS-0094 Figure 2 Effects of (A) nirmatrelvir ritonavir and (B) molnupiravir on post-covid 19 outcomesConclusions While nirmatrelvir/ritonavir and molnupiravir are associated with reduced risk of post-COVID-19 conditions in patients with CLD, molnupiravir was generally less effective. Our findings suggest that nirmatrelvir/ritonavir should be prescribed over molnupiravir for patients with stable hepatic conditions."

Clinical • Acute Respiratory Distress Syndrome • Hepatology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

On degree-dependent topological study of line graph of some antiviral COVID-19 drugs. (PubMed, Eur Phys J E Soft Matter) - "This article focuses on the topological characterization of a line graph for antiviral COVID-19 drugs, namely Nirmatrelvir, Molnupiravir, Thalidomide, Theaflavin, Remdesivir, Ritonavir, Chloroquine, Hydroxychloroquine, Arbidol and Lopinavir. A comparison is made between the squared correlation coefficients derived from our curvilinear regression models and those obtained from earlier research. These findings may aid the applicability of newly developed drugs of similar kind, in predicting their physicochemical properties and in improving the associated QSPR studies and hence pave a way to improve treatments against the COVID-19 disease."

Journal • Infectious Disease • Novel Coronavirus Disease

Development and validation of a RP-HPLC method for simultaneous determination of five COVID-19 antiviral drugs in pharmaceutical formulations. (PubMed, Sci Rep) - "A rapid, sensitive, and selective reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the simultaneous determination of five COVID-19 antiviral drugs: favipiravir, molnupiravir, nirmatrelvir, remdesivir, and ritonavir. Comprehensive greenness and practicality evaluations using five assessment tools yielded favorable scores: AGREE (0.70), AGREEprep (0.59), MoGAPI (70%), BAGI (82.5), and CACI (79), indicating good environmental performance and excellent practical applicability for routine pharmaceutical quality control analysis. The multi-tool assessment confirmed the method's environmental friendliness through strategic solvent selection and minimal sample preparation requirements, while demonstrating superior practical implementation characteristics including cost-effectiveness and accessibility in standard analytical laboratories."

Journal • Infectious Disease • Novel Coronavirus Disease

Differential severity of SARS-CoV-2 variant infections in children and adults with COVID-19. (PubMed, J Clin Virol) - "Genome-wide association studies revealed that nonstructural protein 5 (nsp5, also called 3C-chymotrypsin-like protease), the Paxlovid target, and the spike N-terminal domain were strongly associated with severity...One kmer in the spike gene region was conserved in Delta genomes, with the kmer retained in higher proportions in patients with more severe infection. Our results show, with the exception of Delta, decreases in severity associated with SARS-CoV-2 variant infection over time and underscore the potential utility of kmer monitoring to assess variant severity."

Journal • Infectious Disease • Novel Coronavirus Disease • Pediatrics • Respiratory Diseases • SPECC1

Analisi di costo-efficacia di nirmatrelvir/ritonavir in pazienti adulti ad alto rischio di progressione a COVID-19 severo. (PubMed, Glob Reg Health Technol Assess) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease