The validation of artificial anti‐monkeypox antibodies by in silico and experimental approaches

Abstract

As a result of smallpox immunization programs that ended more than 40 years ago, a significant portion of the world's population is not immune. Moreover, due to the lack of anti‐monkeypox drugs and vaccines against monkeypox, the spread of this virus may be the beginning of another challenge. In this study, novel antibodies against monkeypox virus were modeled based on a heavy chain of human antibody and a small peptide fragment. Docking of modeled antibodies with C19L protein showed the range of docking energy, and root‐mean‐square deviation (RMSD) was from −124 to −154 kcal/mL and 4–6 angstrom, respectively. Also, docking of modeled antibodies‐C19L complex with gamma Fc receptor type I illustrated the range of docking energy, and RMSD was from −132 to −155 kcal/ml and 5–7 angstrom, respectively. Moreover, molecular dynamics simulation showed that antibody 62 had the highest stability with the lowest energy level and RMSD. Interestingly, no modeled antibodies had immunogenicity, allergenicity, and toxicity. Although all of them had good stability, only antibodies 25, 28, 54, and 62 had a half‐life of >10 h. Moreover, the interaction between C19L protein and anti‐C19L antibodies (wild‐type and synthetic) was evaluated by the SPR method. We found that K D in synthetic antibodies was lower than wild antibody. In terms of δH°, TδS°, and δG°, the results were consistent with binding parameters. Here, the lowest value of thermodynamic parameters was obtained for antibody 62. These data show that the synthetic antibodies, especially antibody 62, had a higher affinity than the wild‐type antibody.

Exploring monkeypox virus proteins and rapid detection techniques

“…The interaction between the C19L protein and the synthetic and wild-type anti-C19L antibodies was analyzed using SPR. The findings showed that synthetic antibodies’ K D value was lower than wild antibodies, 0.1 and 0.8 nM, respectively, meaning that synthetic antibodies had a higher affinity for MPXV C19L protein ( Shabani et al., 2023 ). In this manner, SPR enabled a label-free, direct, and real-time quantitative assessment of molecular interactions ( Shi et al., 2022 ).…”

“…Likewise, the same study employed SPR to study the affinity of the MPXV L1R protein to GAG. Shabani et al (2023) designed a new synthetic anti-MPXV C19L antibody (antibody 62) based on a heavy chain of human antibodies and a small peptide fragment at its beginning. The docking and molecular simulation analysis of the designed anti-MPXV C19L antibodies were applied to select the one with superior stability.…”

“…Likewise, the same study employed SPR to study the affinity of the MPXV L1R protein to GAG. Shabani et al. (2023) designed a new synthetic anti-MPXV C19L antibody (antibody 62) based on a heavy chain of human antibodies and a small peptide fragment at its beginning.…”