
Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Янв. 29, 2024
Язык: Английский
Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Янв. 29, 2024
Язык: Английский
medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Май 18, 2024
Abstract In the Spring of 2020, United States America (USA) deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Over 500,000 patients were treated with CCP during first year pandemic. this study, estimated number actual inpatient lives saved by treatment in USA based upon weekly use, national mortality data, and reduction data from meta-analyses randomized controlled trials real-world data. We also estimate potential if had been for 100% or used 15% 75% outpatients. Depending on assumptions modeled stratified analyses, was have between 16,476 66,296 lives. The ideal use might as many 234.869 while preventing 1,136,133 hospitalizations. deployment a successful strategy ameliorating impact pandemic USA. This experience has important implications future infectious disease emergencies. Significance statement When struck population lacked immunity, no validated therapies available, high. authorized historical evidence (CP) efficacy findings nationwide registry suggesting that it reduced mortality. However, decision controversial because not clinical trials. we leveraged combined show tens thousands provides powerful basis consider CP
Язык: Английский
Процитировано
4Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 176, С. 116900 - 116900
Опубликована: Июнь 10, 2024
Язык: Английский
Процитировано
4Expert Opinion on Biological Therapy, Год журнала: 2024, Номер 24(8), С. 787 - 797
Опубликована: Авг. 1, 2024
Monoclonal antibody (mAb) therapies proved safe and effective in preventing progression of COVID-19 to hospitalization, but most were eventually defeated by continued viral evolution. mAb combinations those mAbs that deliberatively selected target conserved regions the SARS-CoV-2 spike protein more resilient escape variants as evident longer clinical useful lives.
Язык: Английский
Процитировано
4Clinical Infectious Diseases, Год журнала: 2024, Номер 79(6), С. 1404 - 1407
Опубликована: Авг. 8, 2024
Abstract The COVID-19 pandemic witnessed the greatest deployment of monoclonal antibody (mAb) therapies for an infectious disease, but all were defeated by SARS-CoV-2 evolution. As new mAbs are developed, disease community needs stewardship practices to reduce emergence resistance.
Язык: Английский
Процитировано
4Expert Review of Anti-infective Therapy, Год журнала: 2025, Номер unknown
Опубликована: Фев. 25, 2025
The success in the COVID-19 pandemic containment largely originated from vaccine- and infection-elicited immunity, with SARS-CoV-2 infection only marginally mitigated by availability of antiviral drugs. current lack effective prophylactic therapeutic agents immunocompromised patients highlights need for a radical change design both drug manufacturing clinical trials. In this review authors summarize their suggestions manufacturers, reviewing classes small molecule antivirals passive immunotherapies highlighting limitations unexploited potential. Molecular serological testing can improve appropriateness. Efficacy be improved combining different while preserving economical sustainability. Respiratory delivery should better investigated
Язык: Английский
Процитировано
0Communications Biology, Год журнала: 2025, Номер 8(1)
Опубликована: Март 6, 2025
The emergence of various SARS-CoV-2 variants presents challenges for antibody therapeutics, emphasizing the need more potent and broadly neutralizing antibodies. Here, we employed an unbiased screening approach successfully isolated two antibodies from individuals with only exposure to ancestral SARS-CoV-2. One these antibodies, CYFN1006-1, exhibited robust cross-neutralization against a spectrum variants, including latest KP.2, KP.3 XEC, consistent IC50 values ranging ~1 5 ng/mL. It also displayed broad neutralization activity SARS-CoV related sarbecoviruses. Structural analysis revealed that target shared hotspot but mutation-resistant epitopes, their Fabs locking receptor binding domains (RBDs) in "down" conformation through interactions adjacent RBDs, cross-linking Spike trimers into di-trimers. In vivo studies conducted JN.1-infected hamster model validated protective efficacy CYFN1006-1. These findings suggest activities can be identified exclusively virus exposure.
Язык: Английский
Процитировано
0bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Фев. 6, 2024
Lassa virus is estimated to cause thousands of human deaths per year, primarily due spillovers from its natural host,
Язык: Английский
Процитировано
1Опубликована: Март 4, 2024
Since the beginning of COVID-19 pandemic, extensive drug repurposing efforts sought to identify small molecule antivirals with various mechanisms action. Here we aim review research progress on viral entry and fusion inhibitors that directly bind SARS CoV-2 Spike protein. Early in numerous molecules were identified screens reported be effective vitro or inhibitors. However, given minimal experimental information regarding exact location binding sites Spike, it was unclear what specific mechanism action was, where for some inhibitor candidates. The work countless researchers has yielded great progress, identification many target elements S1 receptor domain (RBD) N-terminal (NTD) disrupt function. In this review, will also focus highlighting inhibition S2 function, either by disrupting formation postfusion conformation alternatively stabilizing structural prefusion prevent conformational changes associated We highlight experimentally validated S1/S2 interface subunit. While most mutations protein date variants concern (VOCs) have been localized subunit, subunit sequence is more conserved only a few observed proximity sites. Several recent targeting shown robust activity over VOC mutant strains and/or greater broad spectrum antiviral other distantly related coronaviruses.
Язык: Английский
Процитировано
1Viruses, Год журнала: 2024, Номер 16(5), С. 712 - 712
Опубликована: Апрель 30, 2024
Since the beginning of COVID-19 pandemic, extensive drug repurposing efforts have sought to identify small-molecule antivirals with various mechanisms action. Here, we aim review research progress on viral entry and fusion inhibitors that directly bind SARS-CoV-2 Spike protein. Early in numerous small molecules were identified screens reported be effective vitro or inhibitors. However, given minimal experimental information regarding exact location binding sites Spike, it was unclear what specific mechanism action where for some inhibitor candidates. The work countless researchers has yielded great progress, identification many target elements S1 receptor-binding domain (RBD) N-terminal (NTD) disrupt function. In this review, will also focus highlighting inhibition S2 function, either by disrupting formation postfusion conformation alternatively stabilizing structural prefusion prevent conformational changes associated We highlight experimentally validated S1/S2 interface subunit. While most substitutions protein date variants concern (VOCs) been localized subunit, subunit sequence is more conserved, only a few observed proximity sites. Several recent targeting shown robust activity over VOC mutant strains and/or greater broad-spectrum antiviral other distantly related coronaviruses.
Язык: Английский
Процитировано
1Clinical Infectious Diseases, Год журнала: 2024, Номер unknown
Опубликована: Май 10, 2024
Journal Article Accepted manuscript Anti-Spike monoclonal antibody monotherapies and immune escape risk minimization strategies Get access Arturo Casadevall, Casadevall Department of Molecular Microbiology Immunology, Johns Hopkins Bloomberg School Public Health, Baltimore, MD 21205, USA corresponding author: [email protected]. https://orcid.org/0000-0002-9402-9167 Search for other works by this author on: Oxford Academic PubMed Google Scholar Daniele Focosi North-Western Tuscany Blood Bank, Pisa University Hospital, Pisa, Italy Clinical Infectious Diseases, ciae254, https://doi.org/10.1093/cid/ciae254 Published: 13 May 2024 history Received: 26 March Accepted: 06
Язык: Английский
Процитировано
1