Flavonoids as magical bullets: In silico ADMET profile and molecular docking study against hMPX Virus

As zoonotic diseases become a bigger threat to human survival and monkeypox and other poxviruses become more common, we need to look into pharmacopoeia more to find ways to treat these diseases. The variola virus, which causes smallpox, closely links with the monkeypox virus (MPXV), an orthopoxvirus. Nigeria observed the cases on 7th May, 2022. This study used a virtual screening approach to identify potential treatments for this virus using natural products. We extracted the proteins from the NCBI and PDB databases. The PBD files of phytochemicals were downloaded from the IMPPAT web server. The SWISS ADMET Server assessed drug-likeness and pharmacokinetic properties. Four host proteins and eight viral proteins were chosen to bind to 26 flavonoid phytochemicals after being screened by pharmacophore, pharmacokinetic, and We used the GASS web server to assess the active site.using the GASS web server. The docking was done by PyRx software embedded with AutoDockVina 4.0 after creating the grid box for individual proteins. At the conclusion of the analysis, Chrysoeriol (IMPHY004433) demonstrated the optimal docking pose with DNA polymerase (8HG1), scoring -8.6. The drug Galanganal (IMPHY000021) exhibited the lowest docking score with Ser/Thr kinase (OPG198), with a -5.1 score. There are two drugs, genistein (IMPHY004643) and 6-hydroxyluteolin (IMPHY005447). Genistein has the best docking poses with VPS54 (with a score of -7.0), while 6-hydroxyluteolin has the best docking poses with C2L (with a score of -9.6 and host-range proteins C7L and OPG027) (with scores of -6.5 and -8.0). The ligands were shown to hydrogen bond, alkylate, and pi-pi interact with their targets. In conclusion, Chrysoeriol, galangin, genistein, and 6-hydroxyluteolin can be good candidates against the human monkeypox virus. There is a need to perform an in vitro antiviral test to assess the antiviral activities of these lead flavonoids.