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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]
  ADI-55689 Pseudotypes and WT SARS viruses in vitro Neutralized SARS-CoV, SARS-CoV-2, bat SARS-like WIVI in cells [79]
  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 [80, 81]
  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]
  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 [90, 94]
  Multiple candidates (Nb30, Nb56 trimers) Pseudotypes in vitro Neutralized SARS-CoV-2 and VOC (UK and South African variants) in cells [91]
  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]
  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]
  ACE2(740)-Fc Pseudotypes and WT SARS viruses in vitro Neutralized SARS-CoV-2 and other ACE2-utilizing CoVs in cells [102]
  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 [106, 107]
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 [122, 123]
  IPB-01, IPB-02 Pseudotypes of SARS viruses in vitro Inhibited SARS-CoV and SARS-CoV-2 entry in cells [124]
  (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]
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