Computational and Rational Design of Single-Chain Antibody against Tick-Borne Encephalitis Virus for Modifying Its
Ivan K Baykov1, Pavel Y Desyukevich1, Ekaterina E Mikhaylova1
1Laboratory of Molecular Microbiology, Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, Russia.
Abstract:
Tick-borne encephalitis virus (TBEV) causes 5-7 thousand cases of human meningitis and encephalitis annually. The neutralizing and protective antibody ch14D5 is a potential therapeutic agent. This antibody exhibits a high affinity for binding with the D3 domain of the glycoprotein E of the Far Eastern subtype of the virus, but a lower affinity for the D3 domains of the Siberian and European subtypes. In this study, a 2.2-fold increase in the affinity of single-chain antibody sc14D5 to D3 proteins of the Siberian and European subtypes of the virus was achieved using rational design and computational modeling. This improvement can be further enhanced in the case of the bivalent binding of the full-length chimeric antibody containing the identified mutation.
