Monteil, VanessaEaton, BrettPostnikova, ElenaMurphy, MichaelBraunsfeld, BenedictCrozier, IanKricek, FranzNiederhofer, JanineSchwarzbock, AliceBreid, HeleneDevignot, StephanieKlingstrom, JonasThalin, CharlotteKellner, Max JChrist, WandaHavervall, SebastianMereiter, StefanKnapp, SylviaSanchez Jimenez, AnnaBugajska-Schretter, AgnesDohnal, AlexanderRuf, ChristineGugenberger, RomanaHagelkruys, AstridMontserrat, NuriaKozieradzki, IvonaAli, Omar HasanStadlmann, JohannesHolbrook, Michael RSchmaljohn, ConnieOostenbrink, ChrisShoemaker, Robert HMirazimi, AliWirnsberger, GeraldPenninger, Josef M.2022-07-122022-07-122022-07-04Monteil, Vanessa;Eaton, Brett;Postnikova, Elena;Murphy, Michael;Braunsfeld, Benedict;Crozier, Ian;Kricek, Franz;Niederhofer, Janine;Schwarzbock, Alice;Breid, Helene;Devignot, Stephanie;Klingstrom, Jonas;Thalin, Charlotte;Kellner, Max J;Christ, Wanda;Havervall, Sebastian;Mereiter, Stefan;Knapp, Sylvia;Jimenez, Anna Sanchez;Bugajska-Schretter, Agnes;Dohnal, Alexander;Ruf, Christine;Gugenberger, Romana;Hagelkruys, Astrid;Montserrat, Nuria;Kozieradzki, Ivona;Ali, Omar Hasan;Stadlmann, Johannes;Holbrook, Michael R;Schmaljohn, Connie;Oostenbrink, Chris;Shoemaker, Robert H;Mirazimi, Ali;Wirnsberger, Gerald;Penninger, Josef M. Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants. Embo Molecular Medicine, 2022-e15230https://hdl.handle.net/2445/187538The recent emergence of multiple SARS-CoV-2 variants has caused considerable concern due to both 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, Delta, and Omicron, 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 all current 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.application/pdfengcc by (c) Vanessa Monteil et al., 2022http://creativecommons.org/licenses/by/3.0/es/Assaigs clínicsCOVID-19VacunesClinical trialsCOVID-19Vaccinesinfo:eu-repo/semantics/preprint2022-07-12info:eu-repo/semantics/openAccess6554242