In silico investigation hit anti-SARS-CoV-2 activity of molecules isolated from Africa flora Marthe Prudence Elionore Koubitobtob, Désiré Bikele Mama, Ndom Jean Claude Department of Chemistry, University of Douala, Cameroon In a context of high comorbidities and social promiscuity like Africa, preparation must be made to handle any deadly pandemics as the case of coronavirus. Ethnobotanical proofs has led to the enumeration of the antiSARS- COV2 bioactive structures (Oyereet al., 2021). RNA-dependent RNA polymerase (RdRp), is a key component of the virus' replication machinery which is being exploited for drug targets (Dai et al. , 2020). This study is devoted to search for new anti-SARS-COV2 molecules in our chemical library of African medicinal plants with good pharmacokinetic and toxicity parameters and good interaction with the RNA-dependant RNA polymerase target protein. We built a chemical library based on a similarity of anti-covid-19 ethnobotanically (Oyereet al., 2021). For molecular screening we proceeded to the analysis of the pharmacokinetic and toxicity parameters (ADMET) by calculating the values of the descriptors of each parameter which we then analyzed using tools of Rapid medicinal screening constraints (Lipinski, opreah and verdonk rules successively). To study the interaction between the hit compound and the protein receptor, we used the docking method. A molecular library from 42 bioactive molecules divided into eight families (Alkaloids, Diarylheptanoids, Flavonoids, Phenolics, Saponin, Diterpenoids, Triterpenoids, Xanthone) was belt. The tryptanthrin was the unique molecule meeting all these initial constraints, such as the ability to diffuse in a passive way, the crossing of the blood brain barrier, a good penetration into kidney cells and easy elimination. The human ether-a go-go related gene encoding a potassium ion (HERG K + ) reveals the fact that the tryptanthrin is not potentially toxic for the heart. In addition, the binding to human serum albumin (log K HSA ) parameter indicates an adequate binding of the tryptanthrin to plasma-protein. Its circulation in the blood stream is appreciable. The logarithm of IC 50 of the tryptanthrin (0.06) lower than that of the remdesivir (0.07) and the galidesivir (0,31 μM) justifies its lower toxicity compared to these two market reference drugs. Examination of interaction between tryptanthrin and RNA-dependant RNA polymerase target protein by the mean of the Docking guarantees its good binding of the molecule in the pocket and consequently its anti-SARS-COV2
good activity. References
1. Dai, W., Zhang, B., Jiang, X.-M., Su, H., Li, J., Zhao, Y., Xie, X., Jin, Z., Peng, J., Liu, F., Li, C., Li, Y., Bai, F., Wang, H., Cheng, X., Cen, X., Hu, S., Yang, X., Wang, J., Liu, X., Xiao, G., Jiang, H., Rao, Z., Zhang, L.-K., Xu, Y., Yang, H., Liu, H., 2020. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science 368, 1331– 1335. https://doi.org/10.1126/science.abb4489 2. OyereT. E., SmithB.B, FideleNK. 2021. Natural Products asPotential Lead Compounds for Drug Discovery Against SARS‑CoV‑2. Natural Products and Bioprospecting 11:611–628. https://doi.org/10.1007/s13659-021-00317-w
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