Antiviral Synthetic RNP Decoy Granules Prevent Infection by the Delta and Omicron Variants

About three years into the COVID pandemic, the new virus is becoming an endemic pathogen. This is due to the emergence of new variants, some more infectious or virulent than the previous ones. New variants can escape antibodies produced by a vaccine reaction or used in treatments such as Regeneron. Paxlovid, a drug that inhibits a bottleneck protein in coronavirus replication, reduces severe illness but promotes reinfection. The current pharmaceutical course will result in an array of variant-dependent booster shots, vaccines, or drugs.

We have developed a variant-independent antiviral candidate (ACE2P) that can be used against multiple strains of the coronavirus. In doing so, we first developed a methodological pipeline which allowed us to screen antiviral candidates in lab conditions. The pipeline consists of a cell-free and virus-free assay (VEx beads), based on fluorescent polystyrene beads coated with the viral receptor-binding domain (RBD).

Of the candidate antivirals that were screened using VEx beads, ACE2P clustered around the beads compared to a non-ACE2 control, indicating its selectivity and specificity for the virus. To confirm the antiviral activity of ACE2P, a plaque assay was performed against the Delta and Omicron (BA.1) variants in Vero E6 cells, with and without ACE2P. ACE2P managed to eliminate all infection events for both the Delta and Omicron variants in protein component concentration >10μg/ml, which is comparable to all currently available anti-covid treatments. Consequently, we demonstrated the first pan-variant COVID antiviral, which should remain effective so long as the virus progeny utilizes ACE2 as the cellular receptor.