Table 1 A summary table on SARS-CoV-2 infection targeting strategies

Targeting Spike–ACE2 interaction

 Small SARS-CoV-2 Spike protein molecule of 193 aa long containing ACE2-binding domain (RBD)

Effectively blocked the virus entry in cell cultures

Several studies reviewed in Kruse (2020)

 Anti-ACE2 blocking Ab

Immunization of animals and Ab library screening

Human Ab library screening

Reviewed in Kruse (2020), Xiaojie et al. (2020)

 Soluble ACE2-Fc fusion protein to bind and neutralize S protein

Extracellular domain of human ACE2 fused with the Fc region of the human immunoglobulin IgG1 shows high-affinity binding to the RBD of SARS-CoV-2 and potent neuralization of virus entry in vitro in cell lines

Kruse (2020), Lei et al. (2020)

 Recombinant soluble ACE2 ectodomain

Effectively competes with native

ACE2 on cell surface to block the subsequent fusion steps. Inhibit growth of authentic SARS-CoV-2 in Vero cells and in human organoids

Xiaojie et al. (2020), Monteil et al. (2020)

 Recombinant ACE2 mutants

Either bind Spike with a higher affinity or express a low catalytic activity which preserve ACE2 function in physiological processes

Xiaojie et al. (2020), Monteil et al. (2020), Chan et al. (2020)

 Anti-Spike Ab from convalescent plasma

mAbs from a COVID-19 infected subject 21 days after the onset of disease identified by using Spike protein as a bait

Several studies reviewed in Kruse (2020), Lei et al. (2020)

 Bi-specific fusion protein, ACE-MAB

One arm is human high affinity anti-Spike Ab. The other arm is a truncated ACE2 protein that binds to a different epitope of Spike

Sorrento therapeutics (reviewed in Xiaojie et al. 2020)

Targeting Spike–NRP1 interaction

 Anti-NRP1 neutralizing Ab

Incubation of Caco-2 cells with anti-NRP1 neutralizing mAbs reduced SARS-CoV-2 infection compared to a control mAb targeting avian influenza A virus (H11N3) hemagglutinin

Cantuti-Castelvetri et al. (2020), Daly et al. (2020)

 Small molecule EG00229 acting as a selective NRP1 antagonist

Binds the b1 CendR binding pocket and inhibits VEGF-A binding by NRP1. Incubation of Caco-2 cells with EG00229 reduced the efficiency of SARS-CoV-2 infection

Daly et al. (2020)

 Soluble b1b2 domain of NRP1

When SARS-CoV-2 pseudovirus was preincubated with recombinant, soluble extracellular b1b2 domain of NRP1, the wild type significantly reduced cell infection

Cantuti-Castelvetri et al. (2020)

 Small molecule inhibitors for Spike–NRP1 interaction

Approach similar to the one recently used to identify six compounds which effectively disrupted VEGF-A–NRP-1 interaction

Perez-Miller et al. (2020)