Аннотация:Viral infections represent a constant threat for public health and have a potential forunpredictable emergence and expansion to the pandemic scale. The use of small-molecule antiviraldrugs is one of the most impotant strategies of prophylaxis and treatment of viral infections, adding toor extending the vaccination programs. Combination of phenotypic and target-oriented screening insilico and in vitro allows to achieve the maximal efficiency on the early stages of antiviral drugdiscovery and development. In this presentation, we will present several examples of realisation of thisstrategy with specific emphasis on performance of both in silico and in vitro driven approaches.Analysis of the antiviral activity big data from the publicly available databases with the help ofmachine learning and dimensionality reduction methods [1-4] allowed us to reveal the newchemotypes of inhibitors of reproduction of tick-borne encephalitis virus (TBEV) and otherflaviviruses [4-7], enteroviruses [8], as well as SARS-CoV-2 coronavirus [3, 6, 9]. Antiviral activity ofthese compounds was confirmed experimentally in vitro. We have also developed the in silico and invitro methods for studying the interactions of small molecules with viral protein targets, such as TBEVenvelope protein E and methyl transferase, and SARS-CoV-2 3CLpro protease [9]. These methods canbe applied to study the mechanisms of viral reproduction inhibition, as well as the target-basedscreening. Structural virology approaches are being employed to study the ligand-protein complexes ofthe most potent and promising compounds for further optimisation.Combination of the aforementioned approaches allowed us to establish the integrated workflowof antiviral drug discovery and development, which simplifies the translation of fundamental studiesinto clinically relevant data. A new compound may enter the workflow on each stage to receive thefeedback required for progression in the antiviral pipeline.This study was supported by the State Research Funding for FSASI "Chumakov FSC R&D IBPRAS" (Institute of Poliomyelitis) (projects No. FNZG-2021-0001 & FNZG-2022-0002).