Innovative phytochemicals based In-Silico drug design and molecular dynamics simulation targeting norovirus induced gastroenteritis

Norovirus, a linear non-segmented RNA virus belongs to the family Caliciviridae that causes gastroenteritis. This study offers a computational based de novo drug discovery mediated by random antiviral active compounds screened against the virulent protein (6GVZ), which is one of the main factors influencing the virus's pathogenesis. The target protein was validated through Ramachandran plot with 94 % of residues located in the favored region. Using bioinformatics approaches, cyclocommunol was among the most powerful active chemical drug compounds. This study aims to transform the use of drugs as a possible treatment approach for norovirus infection. The option of cyclocommunol as a drug candidate was screen among 24 antiviral drugs compounds. Cyclocommunol the top candidate with the lowest binding affinity was selected as a drug chemical compound, with -7.8 Kcal/mol binding affinity, -4.27 water solubility, 107.22 Ų TPSA score, 6.71 synthetic accessibility, and high GI absorption; hence cyclocommunol follows the Lipinski rule of five. Toxicity analysis of cyclocommunol predicted that this compound is the least toxic and safe to be used as a drug candidate. Additionally, Molecular Dynamic Simulation (MD) results confirmed the effectiveness of cyclocommunol as a drug against norovirus infection. A 100-nanosecond simulation carried out on the dock complex of 6GVZ and cyclocommunol indicate well stability and good interactions during the whole course of 100 ns simulation. Cyclocommunol can be one of the best active compounds, as proved by the use of different bioinformatics analyses, performed in the current study. Here we report the computational based discovery of cyclocommunol which are used as a potential therapeutic strategy for norovirus infection. Furthermore, we suggest that cyclocommunol-related compounds should test in the future with emphasis on the experimental validation utilizing in vitro and in vivo models.