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

Convergence in age adjusted mortality rates and proportion of all deaths from COVID-19 among patients with hematologic malignancies, 2020-2024 (ASH 2025) - "One retrospective cohort study found no effect of immunosuppression with prednisone, tacrolimus, or mycophenolate mofetil on ventilation, in-hospital mortality or length of stay among hospitalized COVID-19 patients in one hospital system (Andersen et. There was a higher peak AAMR from COVID-19 as a proportion of all deaths in the general population during the heights of the COVID-19 pandemic (2020-2021) than among patients with HM as a share of all HM-associated deaths in the same period across all regions. The all-cause AAMR is higher at baseline among patients with HM, so the effect of COVID-19 may have been smaller in this population as a share of all deaths. Patients known to have HM may access care, take airborne precautions and vaccinate more regularly."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Solid Tumor

Nirmatrelvir-ritonavir addition to acute care formulary: a retrospective, multi-centre evaluation of quantitative economic and qualitative clinical outcomes. (PubMed, J Antimicrob Chemother) - "Economic data from this study of elderly adults with mild-moderate COVID-19 suggest that addition of NMV/r to hospital formulary should be considered to support optimal resources consumption, while the clinical impact of NMV/r availability may be better studied through evaluating mild or moderate COVID-19 disease independently."

Clinical data • Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease

Effectiveness comparison of nirmatrelvir/ritonavir versus molnupiravir in COVID-19 patients with comorbidities in Taiwan: a multi-centre electronic health record study. (PubMed, BMC Infect Dis) - "Data revealed that both nirmatrelvir/ritonavir and molnupiravir demonstrated clinical benefits in treating COVID-19 patients in a real-world setting. Moreover, nirmatrelvir/ritonavir was associated with a lower risk of mortality in COVID-19 patients with specific circumstances."

Journal • Chronic Kidney Disease • CNS Disorders • Diabetes • Hepatology • Infectious Disease • Mental Retardation • Metabolic Disorders • Nephrology • Novel Coronavirus Disease • Psychiatry • Renal Disease • Respiratory Diseases

Factors associated with seeking and receiving home antiviral therapy during the coronavirus disease 2019 (COVID-19) pandemic. (PubMed, Discov Public Health) - "Home antiviral treatment (HAVT: nirmatrelvir/ritonavir [Paxlovid] and molnupiravir [Lagevrio]) for COVID-19 was approved in December 2021 by the U.S. Food and Drug Administration, but ensuing utilization during the Coronavirus Disease 2019 (COVID-19) pandemic was low. Loss of taste or smell was the most important factor among several others associated with seeking HAVT irrespective of COVID-19 test status. The online version contains supplementary material available at 10.1186/s12982-025-01192-3."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Identification of flavonoid-based small molecule inhibitors with dual-targeting capability against RdRp and Mpro of SARS-CoV-2. (PubMed, Bioorg Med Chem Lett) - "Based on this, our study identified two derivatives through pharmacophore alignment between flavonoid scaffolds and the main protease (Mpro) inhibitor 13b: a psoralen-derived lignan (Comp.1) and a novel isoflavone analog (Comp.2), with dual-targeting capability against SARS-CoV-2 RdRp and Mpro...Both compounds maintained inhibitory activity against the PF07321332-resistant L50F/E166V double mutant Mpro, with IC₅₀ fold-change values of 1.23 and 1.18, respectively, compared to an 8.62-fold reduction for PF07321332. However, ADMET evaluation indicated that although compounds met basic physicochemical criteria (including molecular weight, TPSA, and compliance with Lipinski's Rule of Five), they still presented critical toxicological liabilities, including high genotoxicity risk (Comp.1: 0.838 probability) and CYP3A4 inhibition (>0.97), necessitating extensive structural optimization. This study confirms that flavonoid derivatives represent promising starting points..."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Rapid establishment of public sector COVID-19 test-and-treatment programmes across seven low- and middle-income countries: implementation strategies and program monitoring results. (PubMed, BMJ Glob Health) - "The COVID-19 Treatment QuickStart Consortium worked with governments in seven low- and middle-income countries (LMICs), Ghana, Laos, Malawi, Nigeria, Rwanda, Uganda and Zambia, to implement COVID-19 test-and-treat programmes at 776 health facilities, including training over 5000 staff and facilitating a donation of 11 300 courses of the oral antiviral nirmatrelvir/ritonavir for treatment...Challenges included COVID-19 de-prioritisation at the time of programme rollout, test commodity stockouts and expiries, and dwindling national surveillance efforts. Learnings from rapid initiation and scale-up of COVID-19 test-and-treat programmes in these seven countries can be used to inform future pandemic preparedness strategies in LMICs."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Lung-Immune Dual-Humanized Mouse Using Cryopreserved Tissue Enables Infection and Immune Profiling of Human Common Cold Coronaviruses. (PubMed, Adv Sci (Weinh)) - "And the refined model supports robust infection by all four major CCCoVs and demonstrates the therapeutic efficacy of Paxlovid against HKU1...The model also enables validation of virus-specific T cell responses and assessment of SARS-CoV-2 cross-reactivity post-HKU1 infection. Overall, this study establishes a scalable platform using cryopreserved tissues for respiratory virus research, overcoming prior limitations in modeling human-specific tropism and dissecting immune-pathogen interactions."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Transplantation

A patent review of Mpro protease inhibitors for the treatment of COVID-19 infections (2020 - present). (PubMed, Expert Opin Ther Pat) - "Clinically advanced agents including nirmatrelvir, ensitrelvir, simnotrelvir, zevotrelvir and leritrelvir are highlighted alongside structurally novel leads and broad-spectrum candidates. A number of Mpro inhibitors have progressed into preclinical and clinical stages, underscoring the rapid advancement in this field. The accumulation of structural knowledge, chemical diversity and mechanistic insight has laid a robust foundation for future antiviral development and may further enhance the utility of Mpro inhibitors against evolving coronaviruses."

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

A Study to Learn How Paxlovid [Nirmatrelvir-ritonavir/PF-07321332] Works in COVID-19 Patients Who Are Elderly or Have Medical Conditions. (clinicaltrials.gov) - P=N/A | N=99000 | Active, not recruiting | Sponsor: Pfizer

New trial • Real-world evidence • Infectious Disease • Novel Coronavirus Disease

Prevalence of potentially inappropriate use of antiviral therapy with simnotrelvir-ritonavir versus nirmatrelvir-ritonavir in hospitalised patients: a retrospective study in Beijing, China. (PubMed, BMJ Open Respir Res) - "About half of the patients use simnotrelvir-ritonavir and nirmatrelvir-ritonavir that might potentially be inappropriate. More extensive research is required to supplement the empirical evidence supporting COVID-19 therapeutics. Additionally, appropriate therapy requires collaboration with pharmacists and education on the appropriate use of COVID-19 therapeutics among physicians and patients."

Clinical • Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Renal Disease

Early-stage Trial to Determine a Safe and Effective Dose for Ratutrelvir in Patients With Mild to Moderate COVID-19 (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Traws Pharma, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease

Thiuram disulfides as prospective inhibitors of 3-chymotrypsin-like cysteine protease: an in-silico approach targeting SARS-CoV-2. (PubMed, In Silico Pharmacol) - "Molecular docking identified DS4, DS6, and DS9 with superior binding affinities (Glide scores: - 5.80, - 5.11, and - 5.17 kcal/mol, respectively) compared to nirmatrelvir (- 4.85 kcal/mol)...Thiuram disulfides, especially DS6 and DS9, exhibit promise as 3CLpro inhibitors, warranting further experimental validation. The online version contains supplementary material available at 10.1007/s40203-025-00496-1."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

LC-MS/MS Method Validation for Quantification of Nirmatrelvir in Human Plasma. (PubMed, Int J Anal Chem) - P2 | "The method offers a rapid analysis time of 2 min per sample and provides highly accurate, reproducible results, making it a valuable tool for evaluating the pharmacokinetics of nirmatrelvir in clinical settings. ClinicalTrials.gov identifier: NCT05041907."

Journal • Infectious Disease • Novel Coronavirus Disease

Exploring Nirmatrelvir Derivatives Through P2 Substituent Modifications and Warhead Innovations Targeting the Main Protease of SARS-CoV-2. (PubMed, Arch Pharm (Weinheim)) - "However, other analogs incorporating individual warhead optimizations displayed similar potency. These findings generate valuable insights into the design of robust Mpro inhibitors and support their potential development as broad-spectrum antiviral agents."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Feasibility of the inhibitor development for SARS-CoV-2: a systematic approach for drug design. (PubMed, J Mol Model) - "Currently, drugs like Paxlovid have significant side effects and high costs, so new alternatives are urgently needed...Free energy landscape (FEL) and conformational clustering analysis showed that Mpro undergoes significant conformational changes when bound to quercetin. In this way, a complete drug screening chain will be used to search for potential Mpro inhibitors and obtain computationally validated candidate that can for experimental evaluation COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Computational Insights into the Regioselective Hydroxylation of Nirmatrelvir Metabolized by Cytochrome P450 3A4. (PubMed, J Chem Inf Model) - "Our simulation results revealed key insights into the spatial proximity between nirmatrelvir's carbon atoms and the reactive iron(IV)-oxo species (Compound I, Cpd I), with the C23 position showing the greatest accessibility, suggesting a strong preference for this site. Density functional theory (DFT) and quantum mechanics/molecular mechanics (QM/MM) calculations further demonstrated that the transition state for C23 hydroxylation possesses the lowest activation energy barrier, consistent with the experimentally observed regioselectivity in metabolite formation."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CYP3A4

Structural Analysis of Inhibitor Binding to the Feline Enteric Coronavirus (FECV) Main Protease. (PubMed, Viruses) - "This study presents crystal structures of four clinically relevant inhibitors-GC376, PF-00835231, nirmatrelvir, and ibuzatrelvir-bound to Mpro from the feline coronavirus strain FECV-UU23. We therefore propose to incorporate sterically constrained, functionally tailored heterocyclic moieties at the P3 site of known inhibitors which can optimally engage Q187, P188, and S189 residues of the S4 loop. The findings presented enhance understanding of inhibitor specificity and reinforce the promise of these inhibitor scaffolds for developing antivirals against feline coronavirus strains, with possible applications in broad-spectrum coronavirus therapy."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Screening-Identified Oxazole-4-Carboxamide KB-2777 Exhibits In Vitro Anti-Coronavirus Activity. (PubMed, Pharmaceutics) - "We compared TOA regimens (full, pre, co, post), evaluated combinations with nirmatrelvir (NL63) or GS-441524 (OC43) using ZIP scores, and profiled infection-context transcripts (IL6, IFNB1, ISG15, NRF2/antioxidant, UPR). KB-2777 shows reproducible cell-based anti-coronavirus activity across α/β lineages, a TOA signature consistent with early post-entry host modulation, and favorable, non-antagonistic combinability with DAAs. These findings support target deconvolution, SAR/ADME optimization, and evaluation in primary airway and in vivo models."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • IL6

Dual Inhibitory Potential of Conessine Against HIV and SARS-CoV-2: Structure-Guided Molecular Docking Analysis of Critical Viral Targets. (PubMed, Viruses) - "Ligands (conessine; positive controls: dolutegravir for HIV-1, nirmatrelvir for SARS-CoV-2) were prepared with standard protonation, minimized, and docked using AutoDock Vina v 1.2.0exhaustiveness 4; 20 poses). ADMET suggested conessine has excellent permeability/BBB access (high logP), but liabilities include poor aqueous solubility, predicted hERG risk, and CYP2D6 substrate dependence.Conessine operates as a hydrophobic, multi-target wedge with the most favorable computed engagement at HIV-1 PR/RT and the SARS-CoV-2 spike RBD, while maintaining stable poses at Mpro and RdRp. The scaffold merits medicinal-chemistry optimization to improve solubility and de-risk cardiotoxicity/CYP interactions, followed by biochemical and cell-based validation against prioritized targets."

Journal • Cardiovascular • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

EXPRESS: Early Blood RNA Clearance and Protein Fraction Profiles Predict Treatment Outcomes in Cats with Effusive FIP. (PubMed, J Feline Med Surg) - "Antiviral treatment included GS-441524, remdesivir, molnupiravir, or adjunctive nirmatrelvir. Persistence of blood viral RNA 2 weeks after treatment, together with opposing changes in α2- and γ-Glb fractions, emerged as predictors of treatment outcomes.Conclusions and relevanceBaseline blood N gene RNA loads and serum Glb fractions have potential as early prognostic indicators in effusive FIP. These results support combining viral and host biomarkers to improve predictions and monitoring."

Journal • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease

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=8252912 | Completed | Sponsor: Pfizer | Recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Feb 2025 | Trial primary completion date: Dec 2025 ➔ Feb 2025

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

Identification and characterization of a SARS-CoV-2 M pro G23 deletion ensitrelvir-resistant mutant. (PubMed, bioRxiv) - "The clinical use of SARS-CoV-2 antiviral drugs is increasingly challenged by the emergence of drug-resistant mutants. Thus, there is a pressing need to identify and characterize antiviral escape SARS-CoV-2 variants, particularly for FDA-approved antivirals. Our study addresses this by employing a luminescent attenuated virus platform (Δ3a7b-Nluc WT) to safely identify and characterize resistance mutations without the concern of using virulent forms of SARS-CoV-2. Using this safe approach, we have identified a G23 deletion (G23del) in SARS-CoV-2 M pro , which mediates resistance to ensitrelvir in vitro and in vivo . Importantly, while G23del was able to confer more than 1,000-fold increased resistance to ensitrelvir, SARS-CoV-2 containing G23del remained sensitive to other M pro (nirmatrelvir) and RdRp (remdesivir) inhibitors. Altogether, this study demonstrates the feasibility of using Δ3a7b-Nluc to safely identify and characterize drug resistant viruses without the..."

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

A SARS-CoV-2 Mpro mutation conferring ensitrelvir resistance paradoxically increases nirmatrelvir susceptibility. (PubMed, Nat Commun) - "Structural analyses reveal critical conformational changes in the catalytic loop (Ile136-Val148) and β-hairpin loop (Cys22-Thr26), directly influencing inhibitor binding selectivity. These results highlight differential resistance profiles of Mpro inhibitors, supporting potential sequential or alternative use of nirmatrelvir and ensitrelvir in patients requiring prolonged antiviral treatment."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Nirmatrelvir/Ritonavir Reduces Infection Duration in Hospitalized Hematological Malignancies Patients with Mild-to-Moderate COVID-19: A Retrospective Study (ASH 2024) - P=N/A | "Patients diagnosed with severe COVID-19, or treated with convalescent plasma, azvudine, or molnupiravir, or with unknown vaccination status, were excluded. Other treatment regimens did not achieve a statistically significant difference in time to viral clearance. 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."

Retrospective data • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases

PanoramicNOR: PAxlovid loNg cOvid-19 pRevention triAl With recruitMent In the Community in Norway (clinicaltrials.gov) - P3 | N=2000 | Active, not recruiting | Sponsor: Haukeland University Hospital | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2026 ➔ Jun 2027 | Trial primary completion date: Apr 2024 ➔ Sep 2025

Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases