Since in silico ADMET prediction can help early drug design and evaluation, ADMET properties of the 67 key compounds were predicted by SwissADME and pkCSM. Chemical properties including molecular weight (MW), rotatable bonds count, H-bond acceptors and donors count, TPSA and leadlikeness violations were calculated by SwissADME and shown as Fig. 8A. It is worth mentioning that 21 (31.34 %) compounds passed the stringent lead-like criteria (250 g/mol ≤ MW ≤ 350 g/mol, XLOGP ≤ 3.5 and rotatable bonds ≤ 7), which are excellent candidates for drug discovery (Fig. 7 A). And these lead-likeness compounds were further predicted by pkCSM, with the exception of S3 (low gastrointestinal absorption)
Fig. 7 Chemical properties statistics of hub components in the formulae. A: Molecular weight, B: rotatable bond count, C: H-bond acceptors count, D: H-bond donors count, E: topological polar surface area (TPSA), F: leadlikeness violations, G: pharmacokinetic and toxicity evaluated parameters of 20 leadlikeness compounds by pkCSM; green = good, yellow = tolerable, red = bad. Caco2: Caco-2 Permeability,HIA: Intestinal Absorption (Human), Skin: Skin Permeability, VDss: volume of distribution, FU: Fraction Unbound (Human), BBB: Blood Brain Barrier permeability, CNS: Central Nervous System permeability,TC: Total Clearance, OCT2: Renal Organic Cation Transporter 2, AMES: AMES toxicity, MTDD: Maximum Tolerated Dose (Human), hERG I/II: hERG I and II Inhibitors, LD50: Oral Rat Acute Toxicity (LD50), HT: Hepatotoxicity, SS: Skin Sensitisation, MT: Minnow toxicity. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 8 Schematic (3D and 2D) representation that molecular model of specific compounds of each formulae with COVID-19 proteins. A: M3 and E protein [ion channel], B: M3 and nsp13 [Helicase NCB site], C: S1 and nsp13 [Helicase ADP site], D: S1 and PLpro, E: X2 and Mpro, F: O2 and Mpro. M: MXSG, S: SGMH, X: XCH, O: Others.