Plant‐based antiviral therapy is the current need for holistic health care management, which can be achieved through screening of phytochemicals and designing of antiviral peptides. There exist certain host's factors which are directly involved for rapid viral replication causing worldwide pandemic. A total of 177 phytochemicals from Ocimum sanctum (L.), Tinospora cordifolia (Thunb.) Miers, Cinnamomum camphora (L.) J. Presl., Allium sativum (L.), Curcuma longa (L.), and Aloe vera (L.) Burm. f. were evaluated for their affinity to all viral proteins of H1N1. Applying drug filters and keeping the threshold of such filters relative to the standards, 82 compounds were found suitable for further analysis. Consensus scoring system was used for screening top ligands from 82 compounds, which screened the top 12 compounds. Highly conserved regions (>80%) which were hydrophilic, flexible, antigenic, and also charged were screened out as potent antiviral peptides. The viral proteins were taken as the targets for the modeled peptides for protein–protein docking. Further, host‐pathogen interacting network was constructed to unveil host factors involved in viral replication, from which unique protein clusters representing their involvement in viral reproduction were selected through mapping with pathway databases. Twelve compounds and five peptides were found to be highly effective against all the proteins of H1N1. Based on the uniqueness, 13 clusters of proteins were obtained which are engaged in cellular process, namely, viral reproduction, fructose‐6‐phosphate metabolism, nitrogen compound metabolism, biosynthesis, cellular process, oligodendrocyte development, localization, multiorganism process, primary metabolism, response to unfolded protein, metabolism, and response to protein and catabolism.
