Humanized synthetic nanobody library for antivenom development

Posted by
  Humanized synthetic nanobody library for antivenom development Abstract Humanized synthetic nanobodies are increasingly important in biomedical research and therapeutic antibody development owing to their high specificity, small size, superior tissue penetration, and reduced immunogenicity. In this study, we constructed a humanized synthetic nanobody library by combining eight sub-libraries. Each sub-library comprised four framework regions derived from human immunoglobulin framework sequences, whereas the complementarity-determining regions (CDRs) were designed based on camelid nanobody sequences. The resulting combined library reached a titer of 1.8 × 10 8  CFU/mL, with approximately 80% of clones containing correct inserts. To evaluate the functionality of the library, a synthetic 15-mer peptide mimic (Asp49-41) corresponding to an enzymatic region of Asp49 phospholipase A 2  (PLA 2 ) from snake ( Crotalus atrox ) venom was synthesized and used as the target antigen. Four...

Inhibition of Chikungunya virus nsP2 protease in vitro by scorpion venom peptide pantinin-1

Posted by

 


Inhibition of Chikungunya virus nsP2 protease in vitro by scorpion venom peptide pantinin-1

Abstract

Climate change has facilitated the spread of arboviruses like the Chikungunya virus (CHIKV). CHIKV, a re-emerging virus from the Togaviridae family, has caused numerous global outbreaks. The absence of antiviral therapy against CHIKV poses a significant threat to public health. The cleavage of the viral polyprotein relies on the catalytic activity of nsP2, crucial for viral replication. Therefore the nsP2 protease presents a promising target for antiviral drug development. Animal venom-derived peptides demonstrated potential in combating various diseases including infections, cancer, and neurodegenerative disorders. In this study, we assessed the inhibitory effects of pantinin-1, a peptide derived from the scorpion Pandinus imperator with broad antimicrobial activity, against CHIKV nsP2 protease. Pantinin-1 effectively inhibited CHIKV nsP2 protease, with a half-maximal inhibitory concentration (IC₅₀) of 6.4 ± 2.04 µM and complete inhibition at 175 µM. Further examination revealed that pantinin-1 functions as a competitive inhibitor with low micromolar affinity and exhibited no toxicity up to 20 µM in cell culture. Using docking and molecular dynamics simulations, the protein-peptide interaction was analyzed, and the key residues involved in the protease binding were predicted. These findings underscore the potential of pantinin-1 as a lead candidate targeting nsP2 protease.

Mastalipour, M., Coronado, M. A., Hernández González, J. E., Willbold, D., & Eberle, R. J. (2026). Inhibition of Chikungunya virus nsP2 protease in vitro by scorpion venom peptide pantinin-1. PLOS ONE, 21(4), e0346930. https://doi.org/10.1371/journal.pone.0346930