TY - JOUR T1 - Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants JF - bioRxiv DO - 10.1101/2021.09.10.459744 SP - 2021.09.10.459744 AU - Gerald Wirnsberger AU - Vanessa Monteil AU - Brett Eaton AU - Elena Postnikova AU - Michael Murphy AU - Benedict Braunsfeld AU - Ian Crozier AU - Franz Kricek AU - Janine Niederhöfer AU - Alice Schwarzböck AU - Helene Breid AU - Anna Sanchez Jimenez AU - Agnes Bugajska-Schretter AU - Alexander Dohnal AU - Christine Ruf AU - Romana Gugenberger AU - Astrid Hagelkruys AU - Nuria Montserrat AU - Michael R. Holbrook AU - Chris Oostenbrink AU - Robert H. Shoemaker AU - Ali Mirazimi AU - Josef M. Penninger Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/09/10/2021.09.10.459744.abstract N2 - 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.Competing Interest StatementJ.M.P. declares a conflict of interest as a founder and shareholder of Apeiron Biologics. G.W., R.G., A.S., J.N, A.S.J, and H.B. are employees of Apeiron Biologics. Apeiron holds a patent on the use of ACE2 for the treatment of various diseases and is currently testing APN01 (soluble recombinant human ACE2) for treatment in COVID-19. The other authors do not declare any conflict of interest. ER -