ziresovir (AK0529) / Ark Biosci, Roche - LARVOL DELTA

Punicalin targets RSV glycoprotein and fusion protein at non-overlapping sites to prevent viral escape. (PubMed, Cell Rep Med) - "PUN inhibits the evaluated RSV-A and RSV-B strains, including a clinical isolate, and retains activity against strains resistant to ziresovir, ribavirin, nirsevimab, and palivizumab. These regions do not overlap known resistance hotspots. In RSV-infected mice, nebulized PUN provides sustained respiratory exposure, reduces lung viral loads and pathology, and attenuates inflammatory responses."

Journal • Inflammation • Respiratory Diseases • Respiratory Syncytial Virus Infections

EFFICACY OF ORAL ZIRESOVIR FOR HOSPITALIZED INFANTS WITH RESPIRATORY SYNCYTIAL VIRUS INFECTION: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS (CHEST 2026) - No abstract available

Retrospective data • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

A Study of Ziresovir (AK0529) in High-risk Adult With Respiratory Syncytial Virus (RSV) Infection. (clinicaltrials.gov) - P2/3 | N=290 | Recruiting | Sponsor: Shanghai Ark Biopharmaceutical Co., Ltd.

New P2/3 trial • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Anti-RSV Study in Chinese Patients (ASCENT) (clinicaltrials.gov) - P2 | N=1 | Terminated | Sponsor: Shanghai Ark Biopharmaceutical Co., Ltd. | N=160 ➔ 1 | Unknown status ➔ Terminated; The study was terminated early due to COVID-19-related enrollment disruptions, not as a result of any product safety concerns.

Enrollment change • Trial termination • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Thorough QT/QTc (TQT) Clinical Study to Evaluate the Effects of Ziresovir on Cardiac Repolarization in Healthy Subjects (clinicaltrials.gov) - P1 | N=34 | Completed | Sponsor: Shanghai Ark Biopharmaceutical Co., Ltd. | Not yet recruiting ➔ Completed

Trial completion

Broad-spectrum coronavirus inhibition by RSV fusion inhibitors targeting six-helix bundle formation. (PubMed, Life Sci) - "These findings identify Ziresovir and TMC353121 as mechanistically validated scaffolds that target conserved fusion mechanisms across different viral families. While further optimization is required to enhance their potency against infectious SARS-CoV-2, this study provides a strategic foundation and chemical templates for the development of broad-spectrum fusion inhibitors to combat current and future coronavirus threats."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Prioritization to foster equitable access to RSV preventive monoclonal antibodies and antivirals for children (RSVVW 2026) - "PADO-RSV reaffirmed nirsevimab and clesrovimab as cornerstones of RSV prevention and placed them on the PADO Priority List, while highlighting the need to align product presentations with programmatic requirements for global use, including autodisable features and temperature monitoring. Similar considerations apply to pipeline products, such as TNM001 (PADO Watch List), which needs to align with existing immunization platforms to enable large-scale delivery, with equity metrics integrated into core development planning. PADO also identified a small but progressing pipeline of antivirals: ziresovir emerged as the most advanced candidate based on Phase III data in infants and, despite resistance signals and trial limitations, was added to the Priority List in an age-appropriate formulation, while other Phase II candidates were added to the Watch List. PADO emphasized a strong preference for oral therapies suitable for outpatient and primary care use and underscored the..."

Clinical • Respiratory Syncytial Virus Infections

Respiratory syncytial virus (RSV) antibody and small-molecule drugs: current status of clinical translation and challenges. (PubMed, Front Microbiol) - "We analyze the evolution of immunoprophylaxis from palivizumab to next-generation long-acting antibodies like nirsevimab, which have reshaped prevention strategies. Furthermore, we evaluate small-molecule agents, contrasting the limitations of early fusion inhibitors with the improved efficacy and resistance barriers of emerging polymerase inhibitors such as ziresovir...Moving forward, the field must prioritize multi-target combination therapies to mitigate resistance and establish global surveillance networks. Ultimately, international collaboration is essential to ensure equitable access, sustainable pricing, and the successful implementation of next-generation RSV therapeutics."

Journal • Review • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Molecular mechanism of ziresovir targeting the fusion glycoprotein of respiratory syncytial virus. (PubMed, PLoS Pathog) - "Leveraging this structural insight, we engineered site-directed RSV mutants guided by both the cryo-EM binding model and drug-resistant RSV variants for fusion inhibitors identified in vitro, and demonstrated that these resistant viruses do not replicate as efficient as wild-type RSV and indicated a fitness cost for viral escape from drug treatment. Collectively, these findings unveil the structural mechanism of ziresovir-mediated viral inhibition, providing a framework for developing the next-generation RSV fusion inhibitors."

Journal • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Respiratory syncytial virus in high-risk adults: A critical appraisal of therapeutic options and unmet needs. (PubMed, Respir Med) - "At present, ribavirin remains the only antiviral recommended for treatment in adults, and no mAb has received regulatory authorization for prophylaxis or therapy in this population...Nevertheless, newer drug candidates, including ziresovir, EDP-938, and S-337395, have shown encouraging antiviral activity and acceptable safety in adult studies. By examining both the scientific evidence and the structural factors shaping the current landscape, we emphasize the need for sustained adult-focused clinical development to complement preventive vaccination. Addressing this therapeutic gap will be essential to reduce the burden of RSV disease in high-risk adult populations, particularly as the global population ages."

Journal • Review • Infectious Disease • Pediatrics • Respiratory Diseases • Respiratory Syncytial Virus Infections

Synthetic oxetanes in drug discovery: where are we in 2025? (PubMed, Expert Opin Drug Discov) - "While oxetanes feature famously in the taxol family, it was not until the recent approval of rilzabrutinib that they have been validated in a fully synthetic drug...The regulatory approval of rilzabrutinib and likely approval of ziresovir provide confidence in using oxetanes as important elements in drug design. While oxetanes have so far been incorporated primarily as pendant groups to optimize physicochemical properties, their use as scaffolding and binding elements presents an exciting opportunity. Enhanced synthetic accessibility to oxetane derivatives will expedite their inclusion in drug discovery campaigns."

Journal • Review • Oncology • Respiratory Diseases

Ziresovir: a potent, selective, and oral inhibitor of the respiratory syncytial virus fusion (F) protein (PubMed, Rev Esp Quimioter) - "When administered orally twice daily for 5 days, it produces a clear clinical improvement in bronchiolitis (signs and symptoms) and a decrease in viral load in the respiratory tract. This new antiviral is well tolerated with few adverse effects, but with the development of resistance during treatment in 11-18% of cases, especially at high doses."

Journal • Review • Pulmonary Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Development of a HEp2-CDX Mouse Model With Sustained High RSV Viral Loads for Robust Antiviral Therapeutic Evaluation. (PubMed, J Med Virol) - "Furthermore, the addition of a clinical monoclonal antibody (nirsevimab) and an antiviral drug (ziresovir) showed strong antiviral activity within this animal model. These findings suggest that HEp2-CDX mice, which enable stable RSV infection and replication, serve as useful models for evaluating antiviral therapeutics."

Journal • Preclinical • Infectious Disease • Oncology • Respiratory Diseases • Respiratory Syncytial Virus Infections

Development and Optimization of a Novel Synthetic Route for 2,4-Diamine-quinazoline Containing Ziresovir: A Drug Candidate for the Treatment of Respiratory Syncytial Virus (RSV) Infection. (PubMed, ACS Omega) - "Finally, nucleophilic substitution of compound 19 with 3-amino-3-oxetanylmethylamine yields the target molecule, Ziresovir. This chromatography-free process offers practical advantages, offering a viable pathway for the production of Ziresovir and other quinazoline analogs."

Journal • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Cholesterol-rich lipid rafts mediate endocytosis as a common pathway for respiratory syncytial virus entry into different host cells. (PubMed, Microbiol Spectr) - "Furthermore, reducing cholesterol levels using methyl-β-cyclodextrin, simvastatin, or terbinafine inhibited RSV infection. Notably, combining simvastatin with an RSV fusion protein inhibitor (AK0529) resulted in enhanced antiviral effects both in vitro and in vivo...By meticulously examining various RSV genotypes, we revealed shared mechanisms underlying viral entry, highlighting the significance of cholesterol regulation and its impact on infection inhibition. Our findings also demonstrate enhanced antiviral efficacy through a combined approach targeting both viral entry and cholesterol metabolism."

Journal • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Viral Bronchiolitis in Infants in the Era of Targeted Therapies: What Now and What's Next? (PubMed, Pediatr Pulmonol) - "Understanding and addressing the causes of poor adherence to bronchiolitis guidelines is critical. Future research should aim to integrate evidence-based treatments with options for personalized adjustments. Updated guidelines should reflect emerging interventions and provide rational management pathways until robust evidence from new studies becomes available."

Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

ArkBio's Ziresovir Included into Pediatric RSV Drug Priority List by WHO (PRNewswire) - "In the newly released 'Paediatric drug optimization for respiratory syncytial virus (PADO-RSV) meeting report' by Global Accelerator for Paediatric formulations (GAP-f), the World Health Organization (WHO) host network, ziresovir (10mg) has been included in the PADO-RSV priority list. Ziresovir, developed by Shanghai Ark Biopharmaceutical Co., Ltd. ('ArkBio'), is the first and only RSV antiviral drug to be included in the list. This is the first time WHO has included an anti-RSV drug developed from China in the paediatric drug optimization priority list."

Commercial • Respiratory Syncytial Virus Infections

The Lancet Child & Adolescent Health Publishes Phase III Trial and 24-Month Follow-Up Results of Ziresovir for RSV in Infants Under 6 Months (PRNewswire) - "The Lancet Child & Adolescent Health, a leading international journal in pediatric and adolescent medicine, has published the Phase III clinical trial results of ziresovir, a novel RSV-targeted antiviral drug developed by Shanghai Ark Biopharmaceutical Ltd. The article...presents detailed subgroup analysis of infants under six months of age, following the primary results published in The New England Journal of Medicine in September 2024....Ziresovir's Phase III results mark a significant milestone, representing the first clinical validation of an antiviral's efficacy in hospitalized infants ≤6 months, and demonstrating long-term benefits in reducing recurrent wheezing and asthma."

P3 data • Asthma • Infectious Disease

Efficacy and safety of ziresovir in hospitalised infants aged 6 months or younger with respiratory syncytial virus infection in China: findings from a phase 3 randomised trial with 24-month follow-up. (PubMed, Lancet Child Adolesc Health) - P3 | "Ziresovir had a favourable safety profile and was associated with a significant clinical benefit during the treatment period compared with placebo in patients aged 6 months or younger."

Clinical • Journal • P3 data • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

A Study to Confirm the Effectiveness and Safety of AK0529 in Treating RSV Infections in Hospitalized Infants (clinicaltrials.gov) - P3 | N=180 | Recruiting | Sponsor: Shanghai Ark Biopharmaceutical Co., Ltd.

New P3 trial • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Cost-effectiveness of anti-viral treatment for infants with RSV disease in the United Kingdom. (PubMed, Vaccine) - "Ziresovir is a cost-effective intervention for all infants hospitalised with RSV if priced below £430 per dose and strategies that exclusively treat high-risk- with CLD and CHD infants justify a higher price of £6558 and £9460 respectively. The outcomes are highly sensitive to the efficacy of Ziresovir and can be improved when the full results of the AIRFLO trial are available."

HEOR • Journal • Cardiovascular • Heart Failure • Pulmonary Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Vaccine and therapeutic agents against the respiratory syncytial virus: resolved and unresolved issue. (PubMed, MedComm (2020)) - "Additionally, there have been notable progress in the realm of passive immunoprophylactic antibodies, with the monoclonal antibody nirsevimab receiving regulatory approval for the prevention of RSV infections in infants...This review delineates the advancements and challenges faced in vaccines and therapeutic agents targeting RSV. It aims to provide insights that will guide the development of effective preventive and control measures for RSV."

Journal • Review • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection. (PubMed, N Engl J Med) - P3 | "Ziresovir treatment reduced signs and symptoms of bronchiolitis in infants and young children hospitalized with RSV infection. No safety concerns were identified. (Funded by Shanghai Ark Biopharmaceutical; AIRFLO ClinicalTrials.gov number, NCT04231968.)."

Clinical • Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Thorough QT/QTc (TQT) Clinical Study to Evaluate the Effects of Ziresovir on Cardiac Repolarization in Healthy Subjects (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Shanghai Ark Biopharmaceutical Co., Ltd.

New P1 trial

Systematic Review of the Efficacy and Safety of RSV-Specific Monoclonal Antibodies and Antivirals in Development. (PubMed, Rev Med Virol) - "Results from 59 studies were extracted, covering efficacy and safety data on six mAbs (motavizumab, motavizumab-YTE, nirsevimab, ALX-0171, suptavumab, clesrovimab) and 12 AV therapies (ALN-RSV01, RSV604, presatovir, MDT-637, lumicitabine, IFN-α1b, rilematovir, enzaplatovir, AK0529, sisunatovir, PC786, EDP-938). Moving forward, passive immunisation and treatment options for RSV infection will play a significant role in reducing the health burden of RSV, complementing recent advancements in vaccine development. TRIAL REGISTRATION: PROSPERO registration: CRD42022376633."

Journal • Review • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • IFNA1