Table 1 Prominent examples of viral entry inhibitors that have demonstrated therapeutic or prophylactic efficacy in cross-neutralization, suppression of escape mutants and broad activity against circulating variants and sarbecoviruses
From: Keep out! SARS-CoV-2 entry inhibitors: their role and utility as COVID-19 therapeutics
Inhibitor type | Agent | Study design/model | Main findings | References |
|---|---|---|---|---|
Antibody | ADG-2 | Pseudotypes and WT SARS viruses in vitro and in vivo | Neutralized SARS-CoV, SARS-CoV-2, bat SARSr CoVs, sarbecoviruses and protected mice against SARS-CoV and SARS-CoV-2 | [78] |
| Â | ADI-55689 | Pseudotypes and WT SARS viruses in vitro | Neutralized SARS-CoV, SARS-CoV-2, bat SARS-like WIVI in cells | [79] |
| Â | S2H97, S2X259 | Pseudotypes and WT SARS viruses in vitro and in vivo | Neutralized SARS-CoV-2, all sarbecovirus clades. Prevented escape mutants and neutralized all VOC. Protected Syrian hamsters from SARS-CoV-2 and B.1.351 | |
|  | REGN10987 + REGN10933 | SARS-CoV-2 pseudotypes in vitro | Agents prevented selection of escape mutants in vitro | [82] |
|  | S309 + S304 | Pseudotypes and aunthentic SARS viruses in vitro | Neutralized SARS-CoV-2, SARS-CoV, WIVI pseudotypes as well as live SARS-CoV-2 in cells | [83] |
|  | CV38-142 + COVA1-16 | Pseudotypes and aunthentic SARS viruses in vitro | Neutralized SARS-CoV, SARS-CoV-2, B.1.1.7 and B.1.351 in cells | [84] |
Nanobody | Multiple candidates (e.g. VHH VE) | Pseudotypes and WT SARS viruses in vitro | VE neutralized SARS-CoV, SARS-CoV-2 and escape mutants | [89] |
| Â | Multiple candidates (NB34, 36,N105) | Pseudotypes and WT SARS viruses in vitro | Neutralized SARS-CoV-2 and variants including B.1.1.7 and B.1.351 in cells | |
| Â | Multiple candidates (Nb30, Nb56 trimers) | Pseudotypes in vitro | Neutralized SARS-CoV-2 and VOC (UK and South African variants) in cells | [91] |
| Â | Multiple candidates (S1-1, S1-RBD-15) | Pseudotypes and WT SARS viruses in vitro | Neutralized SARS-CoV, SARS-CoV-2, B.1.351 and escape mutants in cells | [95] |
|  | Multiple candidates (e.g. WNb 2 + 7) | Pseudotypes and WT SARS viruses in vitro and in vivo | Neutralized SARS-CoV-2 in vitro, N501Y D614G variant in vitro and prophylactically reduced viral loads in mice | [96] |
Decoy receptor | sACE22.v2.4 | Pseudotypes and WT SARS viruses in vitro | Neutralized various ACE2-utilizing SARS-related viruses from humans and bats in cells | [102] |
| Â | CTC-445.2d, CTC-445.2t | Pseudotypes and WT SARS viruses in vitro and in vivo | Showed resilience to escape mutants; neutralized SARS-CoV-2 in vitro. Protected mice and hamsters against SARS-CoV-2 | [103] |
| Â | ACE2(740)-Fc | Pseudotypes and WT SARS viruses in vitro | Neutralized SARS-CoV-2 and other ACE2-utilizing CoVs in cells | [102] |
| Â | LCB1 | WT SARS viruses in vitro and in vivo | Neutralized WT SARS-CoV-2 in vitro and prophylactically protected mice against SARS-CoV-2, B.1.1.7 and E484K/N501Y variant | |
Fusion inhibitor | EK1, EK1C4 | Pseudotypes and WT SARS viruses in vitro and in vivo | Inhibited entry of various CoVs including SARS-CoV-2, SARS-CoV, MERS, WIVI, HCoV-NL63, HCoV-0C43 in vitro. Protected mice from MERS, HCoV-0C43, SARS-CoV-2 | |
| Â | IPB-01, IPB-02 | Pseudotypes of SARS viruses in vitro | Inhibited SARS-CoV and SARS-CoV-2 entry in cells | [124] |
| Â | (SARSHRC-PEG4)2-chol | WT SARS-CoV-2 in vitro and in vivo | Inhibited SARS-CoV-2 entry in vitro and prophylactically protected ferrets from SARS-CoV-2 infection | [125] |