COVID-19およびその変種による感染症を1回の吸入投与で治療、あるいは予防することができた A single inhaled dose treated or even prevented infection by COVID-19 and its variants
2022-04-13 ノースウェスタン大学
・計算機で設計され、実験室で改良された新しいタンパク質療法は、ウイルスが細胞に侵入する能力を阻害することで感染を阻止します。このタンパク質は、米国食品医薬品局(FDA)から緊急使用許可を得ている抗体治療薬と同等以上の効力を持ってウイルスを中和しました。注目すべきは、このタンパク質は、多くの臨床抗体が失敗している、試験したすべてのSARS-CoV-2亜種も中和したことです。
・研究者らは、この治療薬をマウスに鼻腔スプレーとして投与したところ、これらの抗ウイルスタンパク質のうち最も優れたものが、感染症状を軽減し、さらには感染を完全に防ぐことを発見した。
この研究結果は、4月12日、Science Translational Medicine誌に掲載されました。
<関連情報>
- https://news.northwestern.edu/stories/2022/04/new-covid-19-nasal-spray-outperforms-current-antibody-treatments-in-mice/
- https://www.science.org/doi/10.1126/scitranslmed.abn1252
多価の設計されたタンパク質がSARS-CoV-2の懸念される変異体を中和し、マウスの感染防御をもたらす Multivalent designed proteins neutralize SARS-CoV-2 variants of concern and confer protection against infection in mice
ANDREW C. HUNT,JAMES BRETT CAS,EYOUNG-JUN PARK,LONGXING CAO,KEJIA WU,ALEXANDRA C. WALLS,ZHUOMING LIU,JOHN E. BOWEN,HSIEN-WEI YEH,SHALLY SAINI,LOUISA HELM,SYAN TING ZHAO,TIEN-YING HSIANG,TYLER N. STARR,INNA GORESHNIK,LISA KOZODOY,LAUREN CARTER,RASHMI RAVICHANDRAN,LYDIA B. GREEN,WADIM L. MATOCHKO,CHRISTY A. THOMSON,BASTIAN VÖGELI,ANTJE KRÜGER,LAURA A. VANBLARGAN,RITA E. CHEN,BAOLING YINGADAM L. BAILEY,NATASHA M. KAFAI,SCOTT E. BOYKEN,AJASJA LJUBETIČ,NATASHA EDMAN,GEORGE UEDA,CAMERON M. CHOW,MAX JOHNSON,AMIN ADDETIA,MARY JANE NAVARRO,NUTTADA PANPRADIST,MICHAEL GALEJR,BENJAMIN S. FREEDMAN,JESSE D. BLOOM,HANNELE RUOHOLA-BAKER,SEAN P. J. WHELAN,LANCE STEWART,MICHAEL S. DIAMOND, DAVID VEESLER ,MICHAEL C. JEWETT AND DAVID BAKER
Science Translational Medicine
Published:12 Apr 2022
DOI: 10.1126/scitranslmed.abn1252
Abstract
New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the coronavirus disease 2019 (COVID-19) pandemic. Here we used a cell-free expression workflow to rapidly screen and optimize constructs containing multiple computationally designed miniprotein inhibitors of SARS-CoV-2. We found the broadest efficacy with a homo-trimeric version of the 75-residue angiotensin converting enzyme 2 (ACE2) mimic AHB2 (TRI2-2) designed to geometrically match the trimeric spike architecture. In the cryo-electron microscopy structure, TRI2 formed a tripod on top of the spike protein which engaged all three receptor binding domains (RBDs) simultaneously as in the design model. TRI2-2 neutralized Omicron (B.1.1.529), Delta (B.1.617.2), and all other variants tested with greater potency than that of monoclonal antibodies used clinically for the treatment of COVID-19. TRI2-2 also conferred prophylactic and therapeutic protection against SARS-CoV-2 challenge when administered intranasally in mice. Designed miniprotein receptor mimics geometrically arrayed to match pathogen receptor binding sites could be a widely applicable antiviral therapeutic strategy with advantages over antibodies and native receptor traps. By comparison, the designed proteins have resistance to viral escape and antigenic drift by construction, precisely tuned avidity, and greatly reduced chance of autoimmune responses.
