The introduction of INF inhibitors has revolutionized the treatment of some chronic inflammatory diseases,e.g.,rheumatoid arthritis and Crohns disease.However,immunogenics ty is one of the important mechanisms behind treatment failure,and generally,switching to another TNF inhibitor will be the first choice for patients and doctors,which results in unmet need for novel anti-TNF agents.Small antibody molecules with less number of epitope may be valuable in less immunogenicity.In this study,with the help of computer-guided molecular design,single-chain variable fragment(scFv)TSA2 was designed using consensus frameworks of human antibody variable region as scaffold to display anti-TNF antagonistic peptides.TSA2 showed evidently improved bioactivity over TSA1(ami-TNF scFv explored before)and almost similar activity as S-Remicade(the scFv form of Remi-cade,anti-TNF antibody approved by FDA),especially in inhibiting TNF-induced cytotoxicity and NF-κB activation.Hitman antibody consensus frameworks with less immunogenicity have been used in the designing of VH domain antibody,scFv TSA1 and TSA2.A serial of TNF-relatcd works convinced us that the novel design strategy was feasible and could be used to design inhibitors targeting more other molecules than TNF-α.More importantly,these designed inhibitors derived from computer modeling may form a virtual antibody library whose size depends on the number of candidate antagonistic peptides,It will be molecular-targeted virtual antibody library because of the specific antagonistic peptides and the potential antibodies could be determined by virtual screening and then confirmed by biologic experiments.