De novo design mini-binder proteins targeting the capsid-forming domain of type 2 PRRSV nucleocapsid protein to inhibit PRRSV replication in vitro.

Porcine reproductive and respiratory syndrome virus (PRRSV) has caused huge economic losses to swine industry but there is no effective antiviral drug. Nucleocapsid (N) protein is highly conserved in type 2 PRRSV and is considered as an important target for antiviral development. Mini-binders are novel protein drugs de novo designed for a specific protein target using a computational approach, which has great application prospects.

Minibinders targeting Staphylococcus aureus α-toxin exert protective effects in vivo.

Staphylococcus aureus is a leading bacterial pathogen worldwide. It secrets α-toxin, a pore-forming cytotoxin that significantly contributes to the pathogenesis of pneumonia, skin necrosis, and lethal infections. Targeting α-toxin has emerged as a promising strategy for developing therapeutics against S.

De novo design mini-binder proteins targeting the glycoproteins D to inhibit PRV replication in PK15 cells.

The recent resurgence of Pseudorabies virus (PRV) has led to considerable economic losses in pig farms across China. As a zoonotic pathogen, the increasing number of human PRV infection cases highlights the urgent need for effective prevention and treatment strategies. Since PRV entry is initiated when glycoprotein D (gD) binds to cellular receptors such as Nectin-1, blocking this interaction presents a promising strategy for inhibiting PRV replication.

De novo designed mini-binders targeting glyceraldehyde-3-phosphate dehydrogenase of Streptococcus equi ssp. zooepidemicus provided partial protection in mice model of infection.

Streptococcus equi ssp. zooepidemicus (Streptococcus zooepidemicus, SEZ) is an important zoonotic pathogen that greatly threatens the health of pigs in China. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been identified as a critical virulence factor that contributes to the adhesion of SEZ to host.

Rapid discovery of pseudorabies virus inhibitors repurposed from the antimicrobial agent ciprofloxacin.

Pseudorabies virus (PRV) is a significant pathogen impacting swine health and poses high zoonotic risks to humans. Effective antiviral treatments for PRV remain limited, underscoring the need for novel therapeutic strategies. In this study, ciprofloxacin was identified as a repurposed promising candidate with significant in vitro inhibition of PRV replication based on our inference from PNU-183792, an HSV-1 DNA polymerase inhibitor, that quinolones have the potential to act as anti-PRV drugs.

Mini-binders targeting Streptococcus equi ssp. zooepidemicus M-like protein inhibit the bacterial adhesion and exert protective effects in vivo.

Streptococcus equi ssp. zooepidemicus (Streptococcus zooepidemicus, SEZ) is one of the most common pathogens causing streptococcal disease in pigs in China and has been identified as a zoonotic pathogen, and thus poses great threat to the health of humans and pigs. The M-like protein (SzM) is the primary virulence factor of SEZ.

Design of minibinder proteins specific to TNFR1.

TNFα inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. However, the use of TNFα blockade may be accompanied by side effects. The cases of bacterial and viral infections, lymphoproliferative disorders, and anti-TNFα-induced lupus, have been reported among the rheumatoid arthritis or Crohn's disease patients treated with TNFα blockers.

De novo design of mini-binder proteins against IL-2 receptor β chain.

IL-2 regulates the immune response by interacting with different IL-2 receptor (IL-2R) subunits. High dose of IL-2 binds to IL-2Rβγ heterodimer, which induce various side effects while activating immune function. Disrupting IL-2 and IL-2R interactions can block IL-2 mediated immune response.

Development of nanobodies specific to clumping factors A of Staphylococcus aureus by yeast surface display.

The Staphylococcus aureus clumping factor A (ClfA) is a fibrinogen (Fg) binding protein that plays an important role in the clumping of S. aureus in blood plasma. The current anti-infective approaches targeting ClfA are mainly based on monoclonal antibodies but showed less impressive efficacy for clinical applications.

De novo design of a protein binder against Staphylococcus enterotoxin B.

Staphylococcus enterotoxin B (SEB) interacts with MHC-II molecules to overactivate immune cells and thereby to produce excessive pro-inflammatory cytokines. Disrupting the interactions between SEB and MHC-II helps eliminate the lethal threat posed by SEB. In this study, a de novo computational approach was used to design protein binders targeting SEB.

Development of nanobodies against Staphylococcus enterotoxin B through yeast surface display.

Staphylococcus enterotoxin B (SEB) is one of the primary virulence factors of Staphylococcus aureus but there is still a lack of targeted drugs. SEB activates immune cells via interacting with MHC-II on antigen-presenting cells, leading to the production of large amounts of pro-inflammatory cytokines. Blocking the interaction between SEB and MHC-II can avert the overactivation of immune cells.