[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-450428-105":59,"doc-detail-450428-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","development-of-ace2-tropic-betacoronavirus-therapeutics-for-future-pandemic-preparedness","Development of ACE2-tropic betacoronavirus therapeutics for future pandemic preparedness","","Viral pandemics require therapeutics whose efficacy can withstand rapid genetic evolution. During COVID-19, five SARS-CoV-2 monoclonal antibody treatments lost activity within about two years, prompting FDA revocation of their emergency use authorizations. The study presents ReconnAb-multimers, engineered to broadly and potently neutralize betacoronaviruses that use host ACE2, using ACE2-based neutralization with multimeric avidity and a pan-betacoronavirus-binding antibody targeting a conserved spike epitope. Results show neutralization across SARS-CoV-2 variants of concern and related pandemic-potential betacoronaviruses, and protection of female mice after Omicron XBB.1.5 challenge.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/development-of-ace2-tropic-betacoronavirus-therapeutics-for-future-pandemic-preparedness/450428/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/development-of-ace2-tropic-betacoronavirus-therapeutics-for-future-pandemic-preparedness/450428.png","ImageObject",300,407,{"name":92,"@type":93},"\tCallum ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-04","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does the paper address in viral pandemics?","Question",{"text":112,"@type":113},"It targets the challenge of developing therapeutics that retain efficacy despite viral genetic evolution. Prior monoclonal antibody treatments for COVID-19 were rendered ineffective and had emergency use authorizations revoked.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What are ReconnAb-multimers?",{"text":117,"@type":113},"ReconnAb-multimers are a therapeutic design that links a non-neutralizing spike-anchoring Fab, an ACE2-based neutralizing component, and a multimerization domain to enhance avidity and potency.",{"name":119,"@type":110,"acceptedAnswer":120},"How broadly do ReconnAb-multimers neutralize betacoronaviruses?",{"text":121,"@type":113},"They neutralize tested SARS-CoV-2 variants of concern and related pandemic-potential betacoronaviruses that use ACE2 as the host receptor, including SARS-CoV and other listed betacoronaviruses. The study also reports mouse protection against Omicron XBB.1.5 challenge.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},450428,1790765504,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},137451211410,"https://ap-avatar.wpscdn.com/avatar/2000bb0a9246f588df?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786362646172706240","Article [https://doi.org/10.1038/s41467-025-66805-6](https://doi.org/10.1038/s41467-025-66805-6)  \nDevelopment ofACE2-tropicbetacoronavirus therapeutics for future pandemic preparedness  \nReceived: 24 March 2025  \n\n| Accepted: 14 November 2025 |\n| --- |\n| |\n| Check for updates |\n\nAshley Utz 1,2,3, Matt Armbrust 4, Thuy-TienT. Nguyen 2,5, Mary Kate Morris6, Chris O. Matthews 2,7, Pallavi Kompella 4, Zheng Cao2,5, Ji Won Ha 4, Arvie Violette 1,2, R. Camille Brewer8,11, Tobias V. Lanz 8,9,  \nWilliam H. Robinson 8,10, Duo Xu 2,5,12, Carl Hanson6,  \nAdrian Hugenmatter 2,4 & Peter S. Kim 2,5   \nA major challenge during viral pandemicsis the ability to develop therapeutics whose efficacy can withstand viral genetic evolution. During the COVID-19 pandemic, five SARS-CoV-2 monoclonal antibody (mAb) therapeutics were rendered ineffective within a period of 2 years, leading to the U.S. FDA revoking their emergency use authorization. Here, we describe ReconnAbmultimers, a new therapeutic design that broadly and potently neutralize all tested betacoronaviruses that use host ACE2 as their receptor to enter cells. These ReconnAb-multimers have potent neutralization efficacy via avidity, enhanced breadth via a new pan-betacoronavirus-binding antibody that targets a highly conserved epitope on SARS-CoV-2 spike protein, and the potential for clinical development by using a catalytically inactive ACE2 component. We demonstrate that ReconnAb-multimers neutralize all SARS-CoV-2 pseudoviruses and authentic viral variants of concern (VOC) tested, with similar or higher potency than mAbs previously approved by the FDA; neutralize related pandemic-potential betacoronaviruses, including SARS-CoV, WIV1-CoV, PRD-0038, and merbecovirus HKU5-CoV-2; and despite a short halflife, protect female mice against authentic viral challenge with Omicron variant XBB.1.5. Our results highlight ReconnAb-multimers as a broad and highly potent therapeutic that could potentially withstand viral escape against current and future betacoronaviruses that require host ACE2 as a receptor.  \nMonoclonal antibodies (mAbs) were an important treatment option during the COVID-19 pandemic for patients with mild-to-moderate COVID-19 at risk of progression to severe disease1. However, over the course of 2 years, ending with the emergence of Omicron BQ.1 and BQ.1.1 variants in November 2022, FDA emergency use authorization (EUA) for bamlanivimab, REGEN-COV, bamlanivimab / etesevimab, sotrovimab, and ultimately bebtelovimab were all revoked, given that they had lost their antiviral efficacy1. There are currently no marketed  \nmAbs to treat COVID-191. Only pemivibart (Pemgarda) has recently become available, but it is only approved for pre-exposure prophylaxis in moderately to severely immunocompromised patients, not as a treatment option post-infection2.  \nAll of the mAb therapeutics developed for COVID-19 bind to antigenic regions on the receptor binding domain (RBD) of the SARSCoV-2 spike protein that are mutated in emerging variants3,4. In contrast, highly potent mAbs have not been approved by the FDA against  \nA full list of affiliations appears at the end of the paper. e-mail: [kimpeter@stanford.edu](kimpeter@stanford.edu)  \nthe more highly conserved S2 subunit of spike5,6. Several multimeric Angiotensin Converting Enzyme 2 (ACE2) therapeutics have also been developed, but many of them incorporate mutations that enhance binding affinity and neutralization potency ofACE2, which render the therapeutics more susceptible to viral evasion7–15. There is a clear unmet need for novel biologic-based therapeutics that can withstand viral evolution to treat patients at risk of progression to severe COVID- 19. However, beyond the immediacy of the COVID-19 pandemic, to prepare for future pandemics, it would be ideal to develop a more broadly useful therapeutic that could neutralize all current and future SARS-CoV-2 variants, as well as related betacoronaviruses, such as those currently circulating in b","cbCaifNlfhRkkMD0","https://ap.wps.com/l/cbCaifNlfhRkkMD0","pdf",2181188,14,"English","# Background\n## Limitations of current monoclonal antibodies\n## Need for broader therapeutics resistant to viral evolution\n# ReconnAb-multimer design\n## Components and targeting strategy\n## Avidity and conserved epitopes\n# Therapeutic viability and in vitro/in vivo results\n## Neutralization of SARS-CoV-2 VOCs and pseudoviruses\n## Neutralization of related betacoronaviruses\n## Protection in Omicron XBB.1.5 challenge","[{\"question\":\"What problem does the paper address in viral pandemics?\",\"answer\":\"It targets the challenge of developing therapeutics that retain efficacy despite viral genetic evolution. Prior monoclonal antibody treatments for COVID-19 were rendered ineffective and had emergency use authorizations revoked.\"},{\"question\":\"What are ReconnAb-multimers?\",\"answer\":\"ReconnAb-multimers are a therapeutic design that links a non-neutralizing spike-anchoring Fab, an ACE2-based neutralizing component, and a multimerization domain to enhance avidity and potency.\"},{\"question\":\"How broadly do ReconnAb-multimers neutralize betacoronaviruses?\",\"answer\":\"They neutralize tested SARS-CoV-2 variants of concern and related pandemic-potential betacoronaviruses that use ACE2 as the host receptor, including SARS-CoV and other listed betacoronaviruses. The study also reports mouse protection against Omicron XBB.1.5 challenge.\"}]","Development of ACE2-tropic betacoronavirus therapeutics for future pandemic preparedness | PDF",1790733191,35]