Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants
Autor: | Monteil, Vanessa, Eaton, Brett, Postnikova, Elena, Murphy, Michael, Braunsfeld, Benedict, Crozier, Ian, Kricek, Franz, Niederhöfer, Janine, Schwarzböck, Alice, Breid, Helene, Devignot, Stephanie, Klingström, Jonas, Thålin, Charlotte, Kellner, Max J, Christ, Wanda, Havervall, Sebastian, Mereiter, Stefan, Knapp, Sylvia, Sanchez Jimenez, Anna, Bugajska‐Schretter, Agnes, Dohnal, Alexander, Ruf, Christine, Gugenberger, Romana, Hagelkruys, Astrid, Montserrat, Nuria, Kozieradzki, Ivona, Hasan Ali, Omar, Stadlmann, Johannes, Holbrook, Michael R, Schmaljohn, Connie, Oostenbrink, Chris, Shoemaker, Robert H, Mirazimi, Ali, Wirnsberger, Gerald, Penninger, Josef M |
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Jazyk: | angličtina |
Rok vydání: | 2022 |
Předmět: |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
viruses Alpha (ethology) Biology Peptidyl-Dipeptidase A Vacunes Article law.invention Clinical trials law Potency Humans Beta (finance) Neutralizing antibody skin and connective tissue diseases Vaccines SARS-CoV-2 fungi COVID-19 Clinical grade Vaccine efficacy Virology respiratory tract diseases COVID-19 Drug Treatment body regions Recombinant DNA biology.protein Molecular Medicine Angiotensin-Converting Enzyme 2 Assaigs clínics |
Zdroj: | bioRxiv article-version (status) pre article-version (number) 1 EMBO Mol Med. Dipòsit Digital de la UB Universidad de Barcelona |
Popis: | The recent emergence of multiple SARS-CoV-2 variants has caused considerable concern due to reduced vaccine efficacy and escape from neutralizing antibody therapeutics. It is therefore paramount to develop therapeutic strategies that inhibit all known and future SARS-CoV-2 variants. Here we report that all SARS-CoV-2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, and Delta, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human soluble ACE2 (APN01). Importantly, soluble ACE2 neutralized infection of VeroE6 cells and human lung epithelial cells by multiple VOC strains with markedly enhanced potency when compared to reference SARS-CoV-2 isolates. Effective inhibition of infections with SARS-CoV-2 variants was validated and confirmed in two independent laboratories. These data show that SARS-CoV-2 variants that have emerged around the world, including current VOC and several variants of interest, can be inhibited by soluble ACE2, providing proof of principle of a pan-SARS-CoV-2 therapeutic. |
Databáze: | OpenAIRE |
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