In 2019, the novel highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak rapidly led to a global pandemic with more than 346 million confirmed cases worldwide, resulting in 5.5 million associated deaths (January 2022). Entry of all SARS-CoV-2 variants is mediated by the cellular angisin-converting enzyme 2 (ACE2). The virus abundantly replicates in the epithelia of the upper respiratory tract. Beyond vaccines for immunization, there is an imminent need for novel treatment options in COVID-19 patients. So far, only a few drugs have found their way into the clinics, often with modest success. Specific gene silencing based on small interfering RNA (siRNA) has emerged as a promising strategy for therapeutic intervention, preventing/limiting SARS-CoV-2 entry into host cells or interfering with viral replication. Here, we pursued both strategies. We designed and screened nine siRNAs (siA1-9) targeting the viral entry receptor ACE2. SiA1, (siRNA against exon1 of ACE2 mRNA) was most efficient, with up to 90% knockdown of the ACE2 mRNA and protein for at least six days. In vitro, siA1 application was found to protect Vero E6 and Huh-7 cells from infection with SARS-CoV-2 with an up to
- Friedrich, M.
- Pfeifer, G.
- Binder, S.
- Aigner, A.
- Vollmer Barbosa, P.
- Makert, G. R.
- Fertey, J.
- Ulbert, S.
- Bodem, J.
- König, E. M.
- Geiger, N.
- Schambach, A.
- Schilling, E.
- Buschmann, T.
- Hauschildt, S.
- Koehl, U.
- Sewald, K.
Keywords
- Ace2
- Covid-19
- Nsp1
- RNAi
- SARS-CoV-2
- coronavirus
- therapeutic siRNA
