Therapeutic efficacy of antibodies and antivirals against a SARS-CoV-2 Omicron variant

Abstract

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the major antigen stimulating the host's protective immune response. A new SARS-CoV-2 variant, designated Omicron, first identified in South Africa and possess many spike protein mutations. Here, we assessed the efficacy of therapeutic monoclonal antibodies (mAbs) against an Omicron variant in Syrian hamsters. Of the mAbs tested (i.e., REGN10987/REGN10933, COV2-2196/COV2-2130, and S309), only COV2-2196/COV2-2130 efficiently inhibited the replication of the Omicron variant in the lungs of hamsters. We also found that treatment of Omicron-infected hamsters with molnupiravir (an inhibitor of the RNA-dependent RNA polymerase of SARS-CoV-2) or S-217622 (an inhibitor of the main protease of SARS-CoV-2) led to a dramatic reduction of virus replication in the lungs. These findings suggest that treatment with the mAb combination COV2-2196/COV2-2130 or the antiviral compounds molnupiravir and S-217622 may be effective against the Omicron variants.

Characterization and antiviral susceptibility of SARS-CoV-2 Omicron/BA.2

“…For the BA.2 (NCD1288)-infected groups, COV2-2196/COV2-2130 treatment suppressed virus infection in the lungs of the animals [mean reduction in viral titer = 2.9 log 10 (PFU/g)] (Fig. 4c), similar to our previous ndings with BA.1 (NC928) 37 . In addition, S309 and REGN10987/REGN10933, which we previously showed were not effective against BA.1, reduced lung virus titers [mean reduction in viral titer = 2.7 and 2.2 log 10 (PFU/g), respectively], although the difference was not statistically signi cant between the REGN10987/REGN10933-and control mAb-treated groups.…”

“…Sera were also collected at this timepoint and tested in an ELISA for RBD-speci c IgG antibodies, which con rmed successful antibody transfer. Similar to our previous experiment 37 , for the D614G (HP095)-infected groups, treatment with S309, REGN10987/REGN10933, or COV2-2196/COV2-2130 markedly reduced virus titers in the lungs compared to those treated with the control mAb (Fig. 4b).…”

“…We recently evaluated the therapeutic effect of FDA-approved mAbs against a BA.1 variant in hamsters 37 .…”

“…We tested REGN10987/REGN10933, S309 (the precursor of sotrovimab), and COV2-2196/COV2-2130 for their therapeutic e cacy against BA.2. We synthesized these mAbs according to publicly available sequences without modi cations in their Fc regions, as described previously 14,37 . Syrian hamsters were inoculated with 10 3 PFU of CoV-2/UT-HP095-1N/Human/2020/Tokyo (D614G; HP095) or BA.2 (NCD1288), and one day later were injected intraperitoneally with S309 (5 mg/kg), the REGN10987/REGN10933 combination (2.5 mg/kg each), or the COV2-2196/COV2-2130 combination (2.5 mg/kg each) (Fig.…”

Activity of Tixagevimab/Cilgavimab against the Omicron variant of SARS-CoV-2 in a hamster model

“…Overall, our results indicate that AZD7442, when used as pre-exposure prophylaxis, has inhibitory activity in vivo against the Omicron BA.1 variant, although this activity is less than against a B.1 G614 virus. This is in line with previous results obtained in vitro [5][6][7][8][9][10] and a recent in vivo study in which a curative treatment with 5mg/kg of antibody cocktail, synthesized without any modification in their Fc region, efficiently inhibited the Omicron variant replication in lungs of hamsters 13 . The U.S. Food Drug Administration (FDA) has published pharmacokinetic data obtained after intramuscular administration of 300mg of AZD7442 14 , the dose used successfully in the PROVENT clinical trial (NCT04625725) 15 .…”