The AutoDockVina (ADV) and OpenBabel (OB) using mmff94s force-field algorithms (included into the PyRx-0.98/1.0 packages) were employed. ADV and OB were selected because of their high accuracies and world-wide ongoing improvements . In particular ADV docking was employed to: i) initial identification of CSP ligands (L) and cavities (C), ii) quantify ADV-conformer affinities in ~ nM, iii) identify nearby amino acids in ADV docked complexes and iv) confirm the CSP cavities targeted by ADV-conformers. A wide grid of 90x90x90 Å centered to the PyMol / centerofmass, surrounding most of the CSP model molecules (~ blinddocking) was employed for ADV docking. The output ADV-conformer docking-scores in -Kcal/mol were converted to ~ nM affinities by applying the formula, 10 9 *(exp (Kcal/mol/0.592) ). To identify the CSP amino acids nearby 4 Å distance of each ADV-conformer, a Python script was designed to be run in PyMol-opened *.pdb or *.pdbqt files. After preliminary ADV tests, to estimate the percentage of cavities targeted, the following CSP virtual cavities were defined by selected amino acids: Bc (bottom cavity between the 2 largest SP and Cterminal α-helices): 347K and/or 364I and/or 366K, Sc (side of the CSP): 66K and/or 63Y and/or 368I and Tc (top of the TSR): 296T and/or 366S and/or 411Y. The approximated percentages of the targeted cavities by thousands of ADV-conformers were calculated using one PyMol/Python home-script (nearby11.py) . This script calculated cavity percentages by the formula, 100 * number of ADV-conformers in each virtual cavity / total numbers of docked ADV-conformers. The resulting approximations accounted for ~75-120 % of the total numbers of ADV-conformers because of some overlapping between the 3 amino acids defining the cavities. The Plasmodium falciparum reference 3D7-strain circumsporozoite protein (PF3D7_0304600), XM_001351086.1 mRNA was submitted to alphafold. One of the most representative predicted models was chosen for this study. Amino acid 310-375 residues (RIII-RII) aligned to 10 Plasmodium species showed high conservation of their 338 C-369 C and 342 C-374 C disulphide bonds and 37.3% of their amino acid sequences. Blue, main CSP domains. Most of these domains were mapped to Supplementary Materials / GraphycalAbstract.