MINOR COMPOSITION COMPOUNDS OF ALGERIAN HERBAL MEDICINES AS INHIBITORS OF SARS-CoV-2 MAIN PROTEASE: MOLECULAR DOCKING AND ADMET PROPERTIES PREDICTION

A computational predicting of possible inhibitors of the main SARS-CoV-2 protease found in Algerian herbal medicines

“…According to "the rule of 5", an orally active drug may have no more than one violation of the following criteria (Table 3): molecular weight less than 500; not more than 5 H-bond donors, 10 H-bond acceptors and 10 rotatable bonds; an octanol-water partition coefficient log P not greater than 5. The results obtained for all the studied compounds in this work respect Lipinski's rule of five, including warfarin [43]. The N3 inhibitor has three Lipinski violations [30], which is to be expected, since it is a peptide-type inhibitor, characterised by a high MW, and many more than 10 rotational bonds.…”

“…Since the emergence of the Covid -19 pandemic, many phytochemicals were evaluated to find candidates which might be able to combat the primary proteins of SARS-CoV-2 [43][44][45][46][47][48][49][50][51][52]. Several of them have already been shown to display effective activity against SARS-CoV-1 Mpro [44]; others have been evaluated from Algerian herbal medicines [43], from Indian traditional medicine [45,[48][49][50][51], from traditional Vietnamese therapy [52], or from Thailand's National List of Essential Medicines [46] as well as compounds selected from the literature with a wide range of biological activities and which were chosen based on their highest activity according to Dr. Duke's phytochemical and ethnobotanical databases [47].…”

“…Successively, the N3 structure was compared to the docked one (Figure 1a) and 16 interactions were found (Figure 1b [62]). The interactions between warfarin and the Mpro were established previously [43]. For the other interactions between compounds and SARS-CoV-2 main protease, they are shown in Figures 2 (a-f).…”

“…Based on the docking score, only warfarin shows a higher value compared to the N3 inhibitor. The docking results of the best seven molecules based on the docking score show that Warfarin interacts with five residues [43], catalponol with five residues, benzyl salicylate with six, prasterone with two, davana ether with three, chamazulene with three, and rosifoliol with two residues. It is important to notice that the N3 inhibitor forms more than twice the interaction of any of these drug candidates which may infer a weak interaction in case any interaction at all is produced.…”

“…It is important to notice that the N3 inhibitor forms more than twice the interaction of any of these drug candidates which may infer a weak interaction in case any interaction at all is produced. Delving deeper into the analysis of the interactions between warfarin and the Mpro, the interactions include HB with Glu 166, Ser 144 and Cys 145 residues, π-π T-shaped with His 41 residue and π-alkyl with Met 164 residue [43]. Also, the presence of HB and π-π T-shaped interactions in the complex formed by warfarin and Mpro increase the affinity of the complex and may be related with its pharmacological activity.…”