PMID- 36072571
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220910
IS  - 2469-2964 (Electronic)
IS  - 2469-2964 (Linking)
VI  - 7
IP  - 1
DP  - 2022
TI  - An ACE2-IgG4 Fc Fusion Protein Demonstrates Strong Binding to All Tested 
      SARS-CoV-2 Variants and Reduced Lung Inflammation in Animal Models of SARS-CoV-2 
      and Influenza.
PG  - 104-121
LID - 10.20411/pai.v7i1.491 [doi]
AB  - BACKGROUND: The continued emergence of SARS-CoV-2 variants has caused concern 
      that a constantly evolving virus will escape vaccines and antibody therapies. New 
      approaches are needed. METHODS: We created and manufactured an ACE2 extracellular 
      domain (ECD) fragment Fc fusion drug candidate, G921, and engineered the compound 
      for enhanced delivery of drug to peripheral tissues by minimizing the size of the 
      ACE2 ECD and by incorporating an Fc domain to enhance transcytosis. G921 was 
      assessed for binding, neutralization, in vivo anti-inflammatory effect, and 
      pharmacokinetic profile. RESULTS: G921 was expressed as an IgG4 Fc fusion protein 
      presenting two ACE2 domains to ACE2 ligands while avoiding risk of infection via 
      antibody-dependent enhancement. G921 strongly binds to the SARS-CoV-2 Wuhan-Hu-1 
      spike protein and demonstrates further diminished off rate to the spike protein 
      from each of the currently identified variants of concern. G921 demonstrates ACE2 
      enzymatic activity comparable to positive control and binding to the neonatal Fc 
      receptor (FcRn) without binding to low affinity Fc-gamma receptors (FcgammaRs). G921 
      is effective in a concentration-dependent manner in a focus reduction 
      neutralization assay with EC(50)=16.3+/-4.2 microg/mL without cytotoxicity in Vero E6 
      cells when tested at 200 microg/mL in an MTS cell proliferation assay. G921 
      demonstrates statistically significant reduction of lung inflammation in relevant 
      models of both SARS-CoV-2 and influenza. The pharmacokinetic profile demonstrated 
      dose-dependent exposure with a multi-day half-life in monkeys and rats. 
      CONCLUSION: G921 data are consistent with both antiviral and anti-inflammatory 
      modes of action. G921 is a novel approach for the prevention and treatment of 
      COVID-19 and possible other diseases characterized by deficiency of ACE2.
CI  - Copyright (c) 2022 Pathogens and Immunity.
FAU - Merigeon, Emmanuel Y
AU  - Merigeon EY
AD  - Gliknik Inc., Baltimore, MD.
FAU - Yang, Dong
AU  - Yang D
AD  - Regional Biocontainment Laboratory, University of Tennessee Health Science 
      Center, Memphis, TN.
FAU - Ihms, Elizabeth A
AU  - Ihms EA
AD  - Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR.
FAU - Bassit, Leda C
AU  - Bassit LC
AD  - Emory University School of Medicine and Children's Healthcare of Atlanta, 
      Department of Pediatrics, Atlanta, GA.
FAU - Fitzpatrick, Elizabeth A
AU  - Fitzpatrick EA
AD  - Dept. of Microbiology, Immunology and Biochemistry, University of Tennessee 
      Health Science Center, Memphis, TN.
FAU - Jonsson, Colleen B
AU  - Jonsson CB
AD  - Regional Biocontainment Laboratory, University of Tennessee Health Science 
      Center, Memphis, TN.
FAU - Schinazi, Raymond F
AU  - Schinazi RF
AD  - Emory University School of Medicine and Children's Healthcare of Atlanta, 
      Department of Pediatrics, Atlanta, GA.
FAU - Block, David S
AU  - Block DS
AD  - Gliknik Inc., Baltimore, MD.
FAU - Olsen, Henrik S
AU  - Olsen HS
AD  - Gliknik Inc., Baltimore, MD.
LA  - eng
PT  - Journal Article
DEP - 20220823
PL  - United States
TA  - Pathog Immun
JT  - Pathogens & immunity
JID - 101683909
PMC - PMC9438944
OTO - NOTNLM
OT  - ACE2
OT  - COVID-19
OT  - SARS-CoV-2 antiviral agents
OT  - anti-inflammatory
COIS- RFS is a Director of Gliknik Inc. His conflict of interest has been reviewed and 
      approved by Emory University. Neither RFS nor LB received any funding from 
      Gliknik Inc. to conduct any of the studies presented herein. EYM, RFS, HSO, and 
      DSB hold equity in Gliknik Inc.
EDAT- 2022/09/09 06:00
MHDA- 2022/09/09 06:01
PMCR- 2022/08/23
CRDT- 2022/09/08 02:28
PHST- 2021/11/18 00:00 [received]
PHST- 2022/05/02 00:00 [accepted]
PHST- 2022/09/08 02:28 [entrez]
PHST- 2022/09/09 06:00 [pubmed]
PHST- 2022/09/09 06:01 [medline]
PHST- 2022/08/23 00:00 [pmc-release]
AID - pai.v7i1.491 [pii]
AID - 10.20411/pai.v7i1.491 [doi]
PST - epublish
SO  - Pathog Immun. 2022 Aug 23;7(1):104-121. doi: 10.20411/pai.v7i1.491. eCollection 
      2022.