The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (RBD_CoV2) has a higher binding affinity to the human receptor angiotensin-converting enzyme 2 (ACE2) than the SARS-CoV RBD (RBD_CoV). Here, we performed molecular dynamics (MD) simulations, binding free energy (BFE) calculations, and interface residue contact network (IRCN) analysis to explore the mechanistic origin of different ACE2-binding affinities of the two RBDs. The results demonstrate that, when compared to the RBD_CoV2-ACE2 complex, RBD_CoV-ACE2 features enhanced dynamicsand inter-protein positional movements and increased conformational entropy and conformational diversity. Although the inter-protein electrostatic attractive interactions are the primary determinant for the high ACE2-binding affinities of both RBDs, the significantly enhanced electrostatic attractive interactions between ACE2 and RBD_CoV2 determine the higher ACE2-binding affinity of RBD_CoV2 than of RBD_CoV. Comprehensive comparative analyses of the residue BFE components and IRCNs between the two complexes reveal that it is the residue changes at the RBD interface that lead to the overall stronger inter-protein electrostatic attractive force in RBD_CoV2-ACE2, which not only tightens the interface packing and suppresses the dynamics of RBD_CoV2-ACE2, but also enhances the ACE2-binding affinity of RBD_CoV2. Since the RBD residue changes involving gain/loss of the positively/negatively charged residues can greatly enhance the binding affinity, special attention should be paid to the SARS-CoV-2 variants carrying such mutations, particularly those near or at the binding interfaces with the potential to form hydrogen bonds and/or salt bridges with ACE2.

The indispensable role of the SARS-CoV-2 main protease (Mpro) in the viral replication cycle and its dissimilarity to human proteases make Mpro a promising drug target. In order to identify the non-covalent Mpro inhibitors, we performed a comprehensive study using a combined computational strategy. We first screened the ZINC purchasable compound database using the pharmacophore model generated from the reference crystal structure of Mpro complexed with the inhibitor ML188. The hit compounds were then filtered by molecular docking and predicted parameters of drug-likeness and pharmacokinetics. The final molecular dynamics (MD) simulations identified three effective candidate inhibitors (ECIs) capable of maintaining binding within the substrate-binding cavity of Mpro. We further performed comparative analyses of the reference and effective complexes in terms of dynamics, thermodynamics, binding free energy (BFE), and interaction energies and modes. The results reveal that, when compared to the inter-molecular electrostatic forces/interactions, the inter-molecular van der Waals (vdW) forces/interactions are far more important in maintaining the association and determining the high affinity. Given the un-favorable effects of the inter-molecular electrostatic interactions—association destabilization by the competitive hydrogen bond (HB) interactions and the reduced binding affinity arising from the un-compensable increase in the electrostatic desolvation penalty—we suggest that enhancing the inter-molecular vdW interactions while avoiding introducing the deeply buried HBs may be a promising strategy in future inhibitor optimization.

In order to evaluate the feasibility of using sugarcane bagasse (SCB) as a substitute for peat in lily cultivation, this study examines the effects of replacing different amounts of peat (0%, 25%, 50%, 75%, and 100%) with SCB on the physical and chemical properties of the substrate. The impact on the growth of cut flower and bulbs of the oriental lily variety ‘Siberia’ was investigated. The results show that the pH value, organic matter content, and reducing sugar content of the substrate were significantly increased (p < 0.05) when peat was replaced with SCB. Moreover, the bulk density, permeability porosity, water-holding porosity, and EC value, as well as the contents of hydrolyzed nitrogen, available phosphorus, available potassium, exchangeable calcium, and exchangeable magnesium were significantly decreased (p < 0.05). The bulk density (0.15–0.17 g·cm³), total porosity (64.2–69.6%), and water-holding porosity (41.0–48.4%) of the mixed media were in a suitable range. The addition of SCB led to shorter plant height, a thinner stalk, and a smaller leaf and flower diameter. The contents of total chlorophyll, chlorophyll a and b in leaves, as well as the activities of sucrose synthetase (SS) and sucrose phosphate synthetase (SPS) decreased with the increase in SCB in the substrates at different growth stages of lily cut flowers. The correlation analysis showed that, except for bulb height, other quality traits of cut flowers and bulbs were significantly negatively correlated with the pH, organic matter, and reducing sugar content of substrates. Plant height, stem diameter, leaf number, leaf length and width, flower diameter of cut flowers, as well as the fresh weight, starch content, the activities of SS and SPS of bulbs were significantly positively correlated with the bulk density, total porosity, water-holding porosity, and hydrolyzed N content of substrates (p < 0.05). The load factors of the principal components indicated that the diameter of stem and flower, leaf number, the content of chlorophyll a and b, and total chlorophyll of cut flowers and SPS activity in bulbs could be used as the core indicators for evaluating the suitability of lily cultivation substrate. In conclusion, when the proportion of peat replaced with SCB was lower than 50%, the quality of cut flowers and bulbs was the same as that found with whole peat. Thus, SCB has broad application prospects in the soilless cultivation of lily plants.