Algorithm to identify and validate novel cofactors as antiviral targets with examples of candidate and validated HIV-1 IN cellular cofactors at particular stages of validation. The algorithm was used in the validation of LEDGF/p75 and TRN-SR2 as cellular cofactors of HIV-1 IN and in validating LEDGF/p75 as an antiviral target. In case of some candidate cofactors, the experimental intervention verifying affect on HIV replication was accompanied by toxicity. These candidates were excluded from follow-up steps of drug target validation. These proteins can still beinvolved in the HIV life cycle but were not considered priority targets.