ABSTRACT:
Extending the Digital Twin v3.0 published by Morais et al. (IJRPAS, May/2026), this work presents Digital Twin v3.1 — a seven-layer computational framework that expands the Mpro (6LU7) inhibition model into a dual-target paradigm, simultaneously incorporating the S/ACE2 protein (PDB: 6M17) as the second antiviral target of SARS-CoV-2. Layer 6 integrates real CHARMm36 molecular dynamics (MD) data from Li & Cheng (2023) for the alliin–6M17 and allicin–6M17 complexes: neither equilibrates over 100 conformations (in contrast to 6LU7, where alliin equilibrates at ~50 conformations); the mean RMSF in the 17-residue S/ACE2 interface active pocket is 0.857 Å (alliin) and 1.128 Å (allicin), a difference of 0.271 Å (24.9%). Layer 7 introduces three novel metrics: DTIS (Dual-Target Inhibition Score), DTAUC and SVEI (SARS-CoV-2 Viral Entry Inhibition). The Allicin/Al₁₂N₁₂ complex achieves NEFI_dual = 14.8×, DTAUC = 42.03 days·inhib. (vs. 2.84 for free allicin), Peak DTIS = 70.1%, and EDc = −8.10 kcal/mol for S/ACE2 — a more negative binding energy than for Mpro itself (−6.74 kcal/mol). The ACE2/Mpro ratio = 1.20 indicates structural preference of the nanocomplex for the S/ACE2 interface, suggesting that the primary mechanism of action of Allicin/Al₁₂N₁₂ may be viral entry blockade. The Digital Twin-predicted RMSF for Allicin/Al₁₂N₁₂ at the S/ACE2 interface is 0.169 Å — a 6.66-fold reduction below free allicin. The framework remains adaptive: new experimental data (in vitro stability, real GROMACS MD, ADMET) can recalibrate the model within minutes.