An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV
The capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, a...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
|
| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2023.2275598 |
| _version_ | 1827211484738879488 |
|---|---|
| author | Hailong Guo Bomsoo Cho Paul R. Hinton Sijia He Yongjun Yu Ashwin Kumar Ramesh Jwala Priyadarsini Sivaccumar Zhiqiang Ku Kristen Campo Sarah Holland Sameer Sachdeva Christopher Mensch Mohamed Dawod Annalis Whitaker Philip Eisenhauer Allison Falcone Rebekah Honce Jason W. Botten Stephen F. Carroll Bruce A. Keyt Andrew W. Womack William R. Strohl Kai Xu Ningyan Zhang Zhiqiang An Sha Ha John W. Shiver Tong-Ming Fu |
| author_facet | Hailong Guo Bomsoo Cho Paul R. Hinton Sijia He Yongjun Yu Ashwin Kumar Ramesh Jwala Priyadarsini Sivaccumar Zhiqiang Ku Kristen Campo Sarah Holland Sameer Sachdeva Christopher Mensch Mohamed Dawod Annalis Whitaker Philip Eisenhauer Allison Falcone Rebekah Honce Jason W. Botten Stephen F. Carroll Bruce A. Keyt Andrew W. Womack William R. Strohl Kai Xu Ningyan Zhang Zhiqiang An Sha Ha John W. Shiver Tong-Ming Fu |
| author_sort | Hailong Guo |
| collection | DOAJ |
| description | The capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-converting enzyme 2 (ACE2) fused to the IgM Fc. This ACE2 decamer viral trap is designed to inhibit SARS-CoV-2 entry function, regardless of viral RBD sequence variations as shown by its high neutralization potency against all known SARS-CoV-2 variants, including Omicron BQ.1, BQ.1.1, XBB.1 and XBB.1.5. In addition, it demonstrates potency against SARS-CoV-1, human NL63, as well as bat and pangolin CoVs. The multivalent trap is effective in both prophylactic and therapeutic settings since a single intranasal dosing confers protection in human ACE2 transgenic mice against viral challenges. Lastly, this molecule is stable at ambient temperature for more than twelve weeks and can sustain physical stress from aerosolization. These results demonstrate the potential of a decameric ACE2 viral trap as an inhalation solution for ACE2-dependent coronaviruses of current and future pandemic concerns. |
| first_indexed | 2024-03-08T11:51:40Z |
| format | Article |
| id | doaj.art-b32daa709614466280c100d037969216 |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2025-03-21T13:44:23Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-b32daa709614466280c100d0379692162024-06-26T10:39:28ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112210.1080/22221751.2023.2275598An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoVHailong Guo0Bomsoo Cho1Paul R. Hinton2Sijia He3Yongjun Yu4Ashwin Kumar Ramesh5Jwala Priyadarsini Sivaccumar6Zhiqiang Ku7Kristen Campo8Sarah Holland9Sameer Sachdeva10Christopher Mensch11Mohamed Dawod12Annalis Whitaker13Philip Eisenhauer14Allison Falcone15Rebekah Honce16Jason W. Botten17Stephen F. Carroll18Bruce A. Keyt19Andrew W. Womack20William R. Strohl21Kai Xu22Ningyan Zhang23Zhiqiang An24Sha Ha25John W. Shiver26Tong-Ming Fu27IGM Biosciences, Mountain View, CA, USAIGM Biosciences, Mountain View, CA, USAIGM Biosciences, Mountain View, CA, USAIGM Biosciences, Mountain View, CA, USAIGM Biosciences, Mountain View, CA, USATexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USATexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USATexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USAIGM Biosciences, Mountain View, CA, USAIGM Biosciences, Mountain View, CA, USAIGM Biosciences, Mountain View, CA, USAIGM Biosciences, Mountain View, CA, USAIGM Biosciences, Mountain View, CA, USACellular, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, VT, USADepartment of Medicine, Division of Pulmonary Disease and Critical Care Medicine, University of Vermont, Burlington, VT, USADepartment of Medicine, Division of Pulmonary Disease and Critical Care Medicine, University of Vermont, Burlington, VT, USADepartment of Medicine, Division of Pulmonary Disease and Critical Care Medicine, University of Vermont, Burlington, VT, USADepartment of Medicine, Division of Pulmonary Disease and Critical Care Medicine, University of Vermont, Burlington, VT, USAIGM Biosciences, Mountain View, CA, USAIGM Biosciences, Mountain View, CA, USAIGM Biosciences, Mountain View, CA, USAIGM Biosciences, Mountain View, CA, USADepartment of Veterinary Biosciences, The Ohio State University, Columbus, OH, USATexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USATexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USAIGM Biosciences, Mountain View, CA, USAIGM Biosciences, Mountain View, CA, USAIGM Biosciences, Mountain View, CA, USAThe capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-converting enzyme 2 (ACE2) fused to the IgM Fc. This ACE2 decamer viral trap is designed to inhibit SARS-CoV-2 entry function, regardless of viral RBD sequence variations as shown by its high neutralization potency against all known SARS-CoV-2 variants, including Omicron BQ.1, BQ.1.1, XBB.1 and XBB.1.5. In addition, it demonstrates potency against SARS-CoV-1, human NL63, as well as bat and pangolin CoVs. The multivalent trap is effective in both prophylactic and therapeutic settings since a single intranasal dosing confers protection in human ACE2 transgenic mice against viral challenges. Lastly, this molecule is stable at ambient temperature for more than twelve weeks and can sustain physical stress from aerosolization. These results demonstrate the potential of a decameric ACE2 viral trap as an inhalation solution for ACE2-dependent coronaviruses of current and future pandemic concerns.https://www.tandfonline.com/doi/10.1080/22221751.2023.2275598SARS-CoVACE2 viral trapneutralizationviral challengeinhalation |
| spellingShingle | Hailong Guo Bomsoo Cho Paul R. Hinton Sijia He Yongjun Yu Ashwin Kumar Ramesh Jwala Priyadarsini Sivaccumar Zhiqiang Ku Kristen Campo Sarah Holland Sameer Sachdeva Christopher Mensch Mohamed Dawod Annalis Whitaker Philip Eisenhauer Allison Falcone Rebekah Honce Jason W. Botten Stephen F. Carroll Bruce A. Keyt Andrew W. Womack William R. Strohl Kai Xu Ningyan Zhang Zhiqiang An Sha Ha John W. Shiver Tong-Ming Fu An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV Emerging Microbes and Infections SARS-CoV ACE2 viral trap neutralization viral challenge inhalation |
| title | An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV |
| title_full | An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV |
| title_fullStr | An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV |
| title_full_unstemmed | An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV |
| title_short | An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV |
| title_sort | ace2 decamer viral trap as a durable intervention solution for current and future sars cov |
| topic | SARS-CoV ACE2 viral trap neutralization viral challenge inhalation |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2023.2275598 |
| work_keys_str_mv | AT hailongguo anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT bomsoocho anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT paulrhinton anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT sijiahe anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT yongjunyu anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT ashwinkumarramesh anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT jwalapriyadarsinisivaccumar anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT zhiqiangku anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT kristencampo anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT sarahholland anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT sameersachdeva anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT christophermensch anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT mohameddawod anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT annaliswhitaker anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT philipeisenhauer anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT allisonfalcone anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT rebekahhonce anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT jasonwbotten anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT stephenfcarroll anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT bruceakeyt anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT andrewwwomack anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT williamrstrohl anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT kaixu anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT ningyanzhang anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT zhiqiangan anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT shaha anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT johnwshiver anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT tongmingfu anace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT hailongguo ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT bomsoocho ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT paulrhinton ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT sijiahe ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT yongjunyu ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT ashwinkumarramesh ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT jwalapriyadarsinisivaccumar ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT zhiqiangku ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT kristencampo ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT sarahholland ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT sameersachdeva ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT christophermensch ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT mohameddawod ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT annaliswhitaker ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT philipeisenhauer ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT allisonfalcone ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT rebekahhonce ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT jasonwbotten ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT stephenfcarroll ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT bruceakeyt ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT andrewwwomack ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT williamrstrohl ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT kaixu ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT ningyanzhang ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT zhiqiangan ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT shaha ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT johnwshiver ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov AT tongmingfu ace2decamerviraltrapasadurableinterventionsolutionforcurrentandfuturesarscov |