In silico screening of JAK-STAT modulators from the antiviral plants of Indian traditional system of medicine with the potential to inhibit 2019 novel coronavirus

Abstract

Aim. The present study was aimed to identify the lead hits from reported anti-viral Indian medicinal plants to modulate the proteins through the JAK-STAT pathway and to identify the proteins that share the domain with coronavirus (COVID19) associated proteins i.e. 3CLpro, PLpro, and spike protein. Methods. The reported anti-viral plants were screened from the available databases and published literature; their phytoconstituents were retrieved, gene-expression was predicted and the modulated proteins in JAK-STAT pathway were predicted. The interaction between proteins was evaluated using STRING and the network between phytoconstituents and proteins was constructed using Cytoscape. The druglikeness score was predicted using MolSoft and the ADMET profile of phytoconstituents was evaluated using admetSAR2.0. The domain of three proteins i.e. 3CLpro, PLpro, and spike protein of coronavirus was compared using NCBI blastP against the RCSB database. Results. The majority of the phytoconstituents from the anti-viral plants were predicted to target TRAF5 protein in the JAK-STAT pathway; among them, vitexilactone was predicted to possess the highest druglikeness score. Proteins targeted in the JAK-STAT pathways were also predicted to modulate the immune system. Similarly, the docking study identified sesaminol 2-O-β-D-gentiobioside to possess the highest binding affinity with spike protein. Similarly, phylogeny comparison also identified the common protein domains with other stains of microbes like murine hepatitis virus strain A59, avian infectious bronchitis virus, and porcine epidemic diarrhea virus CV777. Conclusion. Although, the present study is based on computer simulations and database mining, it provides two important aspects in identifying the lead hits against coronavirus. First, targeting the JAK-STAT pathway in the corona-infected host by folk anti-viral agents can regulate the immune system which would inhibit spreading the virus inside the subject. Secondly, the well-known targets of coronavirus i.e. 3CLpro, PLpro, and spike protein share some common domains with other proteins of different microbial strains.

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