SARS-CoV-2 is highly homologous to SARS-CoV. To date, the main protease (Mpro) of SARS-CoV-2 is regarded as an important drug target for the treatment of Coronavirus Disease 2019 (COVID-19). Some experiments confirmed that several HIV protease inhibitors present the inhibitory effects on the replication of SARS-CoV-2 by inhibiting Mpro. However, the mechanism of action has still not been studied very clearly. In this work, the interaction mechanism of four HIV protease inhibitors Darunavir (DRV), Lopinavir (LPV), Nelfinavir (NFV), and Ritonavire (RTV) targeting SARS-CoV-2 Mpro was explored by applying docking, molecular dynamics (MD) simulations, and MM–GBSA methods using the broad-spectrum antiviral drug Ribavirin (RBV) as the negative and nonspecific control. Our results revealed that LPV, RTV, and NFV have higher binding affinities with Mpro, and they all interact with catalytic residues His41 and the other two key amino acids Met49 and Met165. Pharmacophore model analysis further revealed that the aromatic ring, hydrogen bond donor, and hydrophobic group are the essential infrastructure of Mpro inhibitors. Overall, this study applied computational simulation methods to study the interaction mechanism of HIV-1 protease inhibitors with SARS-CoV-2 Mpro, and the findings provide useful insights for the development of novel anti-SARS-CoV-2 agents for the treatment of COVID-19.

Transforming growth factor-β (TGF-β) mimetic peptides offer significant therapeutic potential due to their superior pharmacological properties over the native cytokine. Our previous work identified two such peptides, TB1 and TB2, which bind to the type II TGF-β receptor (TβRII) yet elicit distinct cellular responses. To uncover the mechanistic basis for the functional divergence, we employed integrated molecular dynamics (MD) simulations with the AlphaFold3-predicted structures. Our analytical results indicated that TB2 stabilizes a dynamic complex with TβRII and is predicted to facilitate type I receptor (TβRI) engagement possibly involving a critical hydrogen bond between TB2-Gly11 and TβRI-Phe60. The resulting trimeric assembly (TB2–TβRII–TβRI) exhibits a higher relative binding affinity (−67.76 ± 7.70 kcal/mol) and structural stability. In contrast, the TB1–TβRII complex fails to productively engage TβRI. These computational results were experimentally validated. Western blot analysis confirmed that TB2, but not TB1, activates the canonical TGF-β/Smad pathway by enhancing the expression and phosphorylation of Smad3. This study will elucidate the dynamic structural basis for the activity of TGF-β mimetic peptides and suggest TB2 as a promising lead candidate for the rational design of tissue-regenerative therapeutics.

This study introduces a novel recombinant humanised collagen (DuCol) developed through codon optimisation and prokaryotic soluble expression, exhibiting exceptional biocompatibility and bioactivity. Structural integrity was confirmed via RP-HPLC, SEM, and CD spectroscopy. In vitro evaluations revealed DuCol’s dose-dependent enhancement of NIH-3T3 fibroblast proliferation, adhesion, and migration. In a D-galactose-induced ageing rat model, subcutaneous implantation of DuCol showcased time-dependent anti-ageing effects. Early-stage intervention (30 days post-injection) markedly upregulated COL1A1 expression through the TGF-β/Smad3 pathway activation, outperforming poly-l-lactic acid (PLLA) in collagen deposition. Histological analysis revealed 23.4% greater dermal thickness in DuCol-treated groups compared to PLLA at 90 days. While PLLA exhibited sustained collagen stimulation beyond 90 days, DuCol exhibited superior early-phase efficacy (p < 0.001) with comparable safety profiles (no inflammatory response observed through 180-day monitoring). The combinatorial PLLA/DuCol (P&C) formulation synergistically enhanced dermal regeneration, achieving a 31.7% thicker collagen matrix than monotherapy groups. These results underscore the potential of DuCol as a novel implantable filler material for skin repair and regeneration.