Structural implications of SARS-CoV-2 Surface Glycoprotein N501Y mutation within receptor-binding domain [499-505]–computational analysis of the most frequent Asn501 polar uncharged amino acid mutations

The aim of this study was to evaluate the impact of the most frequent Asn501 polar uncharged amino acid mutations upon important structural properties of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Surface Glycoprotein RBD–hACE2 (human angiotensin-converting enzyme 2) heterodimer. Mutations N501Y, N501T and N501S were considered and their impact upon complex solubility, secondary motifs formation and intermolecular hydrogen bonding interface was analyzed. Results and findings are reported based on 50 ns run in Gromacs molecular dynamics simulation software. Special attention is paid on the biomechanical shifts in the receptor-binding domain (RBD) [499-505]: ProThrAsn(Tyr)GlyValGlyTyr, having substituted Asparagine to Tyrosine at position 501. The main findings indicate that the N501S mutation increases SARS-CoV-2 S-protein RBD–hACE2 solubility over N501T, N501 (wild type): (Formula presented.), (Formula presented.). The N501Y mutation shifts (Formula presented.) -helix S-protein RBD [366-370]: SerValLeuTyrAsn into π-helix for t > 38.5 ns. An S-protein RBD [503-505]: ValGlyTyr shift from (Formula presented.) -helix into a turn is observed due to the N501Y mutation in t > 33 ns. An empirical proof for the presence of a Y501-binding pocket, based on RBD [499-505]: PTYGVGY (Formula presented.) 's RMSF peak formation is presented. There is enhanced electrostatic interaction between Tyr505 (RBD) phenolic -OH group and Glu37 (hACE2) side chain oxygen atoms due to the N501Y mutation. The N501Y mutation shifts the (Formula presented.) hydrogen bond into permanent polar contact;(Formula presented.);(Formula presented.). © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Beyond Lyophilization

The company's Lyoguard trays are being used in the production of mAbs;diagnostics tests for COVID-19 virus or antibodies;and some of the key raw materials used in messenger RNA (mRNA) vaccines, including synthetic oligonucleotides, adjuvants, and lipid nanoparticles, he says. [...]it's a question of capacity. Another problem is the fact that lyophilization involves very slow cooling, at a rate of one degree Kelvin per second, says Bill Williams, a professor at the University of Texas and inventor of the thin-film freezing process, which he developed years ago at the Dow Chemical Co. TFF Pharma licensed his technology and commercialized it in 2019. Williams and his team, with corporate and US government funding, are now focusing on research designed to optimize use of thin-film freezing to improve the processing and delivery of biologics, including vaccines, along with the cold chain.

Research on the 6XS6 of the SARS-CoV-2 Spike Protein

The 6XS6 is the structure of the SARS-CoV-2 spike protein. The physiological role of the spike protein is relative to the respiratory syndrome coronavirus and has a stronger infect on the human body than the ancestor virus. The purification of the 6XS6 is in the homo sapiens cell by the affinity chromatography, PBS supplemented and Size Exclusion chromatography. At last, using the Cryo-Electron Microscopy to see the structure. This paper is using the D614G mutation to illustrate the structure of the 6XS6. The N-terminal domain and C-terminal domain of the 6XS6 protein are ALA27 and VAL1137. Furthermore, the mutation doesn't have the hydrogen bond because the Asp614 is substituted by the Gly614, and the molecule that interacts with the Ala 647 may occur. While the 6XS6 structure has lots of non-covalent and disulfide bonds. Comparing the structure of the 6XS6 and 6VXX, both are glycoproteins, have three monomers, have two subunits, and have the same category of expression and classification. The different conformations of the two structures can affect the binding ability with the ACE2. This paper can help the researchers to further understand the structure and function of the 6XS6 which can be used in future experiments. © 2023 SPIE.

Recent advances in the effect of ultrasound on the binding of protein−polyphenol complexes in foodstuff

Foodstuff is a complex system that consists of a variety of nutrients. Protein is the basis of human life and health, which is made up of amino acids combined in different proportional orders. Polyphenols are a class of small molecule active substances with strong pro-life health effects. It has been found that protein and polyphenols can be combined by covalent and non-covalent interactions to form complex delivery carriers. The interaction between the two can effectively improve the physiological activities of proteins and enhance the bio-accessibility of polyphenols. With the maturation of ultrasound technology, several studies have shown that ultrasound can promote the production of protein−polyphenol complexes. To promote the study of protein–polyphenol interactions in foodstuff by ultrasound technology, the preparation methods of protein−polyphenol complexes, the effects of ultrasound on complex generation, and analytical methods were systematically summarized based on an extensive literature review, and further research directions were proposed. It provides the reference for the ultrasound study of protein−polyphenol complexes.

Crystal Growth, Structural, Vibrational, Effects of Hydrogen Bonding(C-H…O and C-H…N), Chemical Reactivity, Antimicrobial Activity, Inhibitory Effects and Molecular Dynamic Simulation of 4-Methoxy-N-(Nitrobenzylidene)-Aniline

The present study aims to provide deeper knowledge about the structural, vibrational, chemical, antimicrobial activity, molecular dynamic simulation and drug likeness of synthesized compound 4-Methoxy-N-(nitrobenzylidene)-aniline. The FT-IR and FT-Raman spectra of 4-Methoxy-N-(nitrobenzylidene)-aniline have been recorded in the powder form in the region 4000–500 cm−1 and 3500–50 cm−1. The vibrational analysis were carried out with the help of normal coordinate analysis (NCA). The molecular geometry, hydrogen bonding interaction and vibrational frequencies have been calculated using the density functional method (DFT/B3LYP) with 6-311 G (D) basis set. The natural bond orbital (NBO), atoms in molecule (AIM), and Hirshfeld surface analysis and RDG were applied to evaluate the relative strength of hydrogen bond interactions and represent their effect on the stabilities of molecular arrangements. Related molecules were compared by computation in order to understand the effect of non-bonded interactions (i.e. intermolecular and intramolecular hydrogen bonding). The HOMO and LUMO analysis was used to determine the charge transfer within the molecule. Furthermore, the in vitro antimicrobial study was carried out for the title compound against Aspergillus niger and Staphylococcus aureus. The antimicrobial activity was confirmed on the compounds with molecular docking (A.niger, S.aureus, Homosapians, Sars-Cov-19 and anticancer) studies and molecular dynamic simulation. The non-linear optical (NLO) properties were also analyzed for the molecules.

Structure property relationship in two thiazole derivatives: Insights of crystal structure, Hirshfeld surface, DFT, QTAIM, NBO and molecular docking studies

Detailed structural and noncovalent interactions in two thiazole derivatives (N-(4-Bromophenyl)-2-(methylthio)thiazole-5-carboxamide and Ethyl-5-((4-bromophenyl)carbamoyl)thiazole-4-carboxylate) are investigated by single crystal X-ray diffraction study and computational approaches. The structure investigation revealed that various interactions like C-H…O, N-H…O, and N-H…N hydrogen bonds and Br…Br interactions are involved in constructing ring motifs to stabilize the crystal packing. Hirshfeld surface analysis and fingerprint plots were carried out to study the differences and similarities in the relative contribution of noncovalent interactions in both the molecules. The FMOs and other global reactive parameters are analyzed for thiazole derivatives. The strength and nature of weak interactions present in the molecule were characterized by RDG-based NCI and QTAIM analyses. Natural bond orbital (NBO) analysis unravels the importance of non-covalent and hyperconjugative interactions for the stability of the molecules in their solid state. Further, molecular docking of N-(4-Bromophenyl)-2-(methylthio)thiazole-5-carboxamide and Ethyl-5-((4-bromophenyl)carbamoyl)thiazole-4-carboxylate with SARS-Covid-19 have been carried out. © 2023 Taylor & Francis Group, LLC.

Elucidating the Role of Noncovalent Interactions in Favipiravir, a Drug Active against Various Human RNA Viruses; a 1H-14N NQDR/Periodic DFT/QTAIM/RDS/3D Hirshfeld Surfaces Combined Study.

Favipiravir (6-fluoro-3-hydroxypyrazine-2-carboxamide, FPV), an active pharmaceutical component of the drug discovered and registered in March 2014 in Japan under the name Avigan, with an indication for pandemic influenza, has been studied. The study of this compound was prompted by the idea that effective processes of recognition and binding of FPV to the nucleic acid are affected predominantly by the propensity to form intra- and intermolecular interactions. Three nuclear quadrupole resonance experimental techniques, namely 1H-14N cross-relaxation, multiple frequency sweeps, and two-frequency irradiation, followed by solid-state computational modelling (density functional theory supplemented by the quantum theory of atoms in molecules, 3D Hirshfeld Surfaces, and reduced density gradient) approaches were applied. The complete NQR spectrum consisting of nine lines indicating the presence of three chemically inequivalent nitrogen sites in the FPV molecule was detected, and the assignment of lines to particular sites was performed. The description of the nearest vicinity of all three nitrogen atoms was used to characterize the nature of the intermolecular interactions from the perspective of the local single atoms and to draw some conclusions on the nature of the interactions required for effective recognition and binding. The propensity to form the electrostatic N-H···O, N-H···N, and C-H···O intermolecular hydrogen bonds competitive with two intramolecular hydrogen bonds, strong O-H···O and very weak N-H···N, closing the 5-member ring and stiffening the structure, as well as π···π and F···F dispersive interactions, were analysed in detail. The hypothesis regarding the similarity of the interaction pattern in the solid and the RNA template was verified. It was discovered that the -NH2 group in the crystal participates in intermolecular hydrogen bonds N-H···N and N-H···O, in the precatalytic state only in N-H···O, while in the active state in N-H···N and N-H···O hydrogen bonds, which is of importance to link FVP to the RNA template. Our study elucidates the binding modes of FVP (in crystal, precatalytic, and active forms) in detail and should guide the design of more potent analogues targeting SARS-CoV-2. Strong direct binding of FVP-RTP to both the active site and cofactor discovered by us suggests a possible alternative, allosteric mechanism of FVP action, which may explain the scattering of the results of clinical trials or the synergistic effect observed in combined treatment against SARS-CoV-2.

Impact of Drug Repurposing on SARS-Cov-2 Main Protease

Abstract: The recent emergence of the severe acute respiratory disease caused by a novel coronavirus remains a concern posing many challenges to public health and the global economy. The resolved crystal structure of the main protease of SARS-CoV-2 or SCV2 (Mpro) has led to its identification as an attractive target for designing potent antiviral drugs. Herein, we provide a comparative molecular impact of hydroxychloroquine (HCQ), remdesivir, and β-D-N4-Hydroxycytidine (NHC) binding on SCV2 Mpro using various computational approaches like molecular docking and molecular dynamics (MD) simulation. Data analyses showed that HCQ, remdesivir, and NHC binding to SARS-CoV-2 Mpro decrease the protease loop capacity to fluctuate. These binding influences the drugs' optimum orientation in the conformational space of SCV2 Mpro and produce noticeable steric effects on the interactive residues. An increased hydrogen bond formation was observed in SCV2 Mpro–NHC complex with a decreased receptor residence time during NHC binding. The binding mode of remdesivir to SCV2 Mpro differs from other drugs having van der Waals interaction as the force stabilizing protein–remdesivir complex. Electrostatic interaction dominates in the SCV2 Mpro−HCQ and SCV2 Mpro–NHC. Residue Glu166 was highly involved in the stability of remdesivir and NHC binding at the SCV2 Mpro active site, while Asp187 provides stability for HCQ binding. © 2022, Pleiades Publishing, Ltd.

Synthesis, crystal structure, DFT calculations, and Hirshfeld surface analysis of an NNN pincer type compound

The novel benzamide derivative NNN pincer type, N,N'-(azanediylbis(2,1-phenylene))bis(3-chlorobenzamide) (H3L), was synthesized from bis(2-nitrophenyl)amine starting material. The pincer ligand was characterized by 1H NMR, 13C NMR, COSY, HMQC, and FT-IR techniques. The geometry of pincer ligand was also confirmed by a single-crystal X-ray diffraction analysis. Structural analysis demonstrate that H3L is monoclinic and space group P21/n with Z = 4. It was find out the molecular conformation of the structure is promoted by intramolecular (N[sbnd]H⋅⋅⋅O, N[sbnd]H⋅⋅⋅N, and C[sbnd]H⋅⋅⋅O) and intermolecular (N(2)-H(2)⋅⋅⋅O(2)i, symmetry code (i) = 1/2 + x, 3/2-y, 1/2 + z) hydrogen bonds. The theoretical study of H3L was performed in the gaseous phase by B3LYP/6-311G(d,p) method to determine the structural properties of the title molecule, as a consequence the obtained data showed that the considerable agreement between the experimental and theoretical results. The reactivity and stability of the molecule were evaluated by calculating the HOMO–LUMO energy gap which was found as 6.5163 eV. In addition, FMO, NBO, NLO, DOS, RDG, MEP surface, and Mulliken atomic charge analyses were carried out. Hirshfeld surface analysis and two-dimensional fingerprint plots were investigated and the obtained data exposed that the most significant contributions to the crystal packing are from C···H/H···C (33.2%), H···H (31.5%), and H···Cl/Cl··H (18.9%) contacts. Furthermore, the molecular docking studies were performed to reveal the binding affinity between the title compound and the main protease (6LU7) of COVID-19 coronavirus. © 2023 Elsevier B.V.

4-(4-methoxyphenyl)-6-methyl-3-phenyl-4H-1,2,4-oxadiazin-5(6H)-one: Synthesis, crystal structure, Hirshfeld surface analysis, noncovalent, ADMET studies and biological evaluation

Oxadiazines are heterocyclic compounds containing two nitrogen and one oxygen atom in a six-membered ring. The synthesis and crystal structure of 4-(4-methoxyphenyl)-6-methyl-3-phenyl-4H-1,2,4-oxadiazin-5(6H)-one (MPMP-OXA) was reported. The organic crystal structure of the synthesized compound was fully characterized by various spectroscopic techniques (Fourier Transform Infrared Spectroscopy, NMR and LC/MS-TOF) and single-crystal X-ray diffraction studies. The MPMP-OXA crystal structure crystallizes in the triclinic system and space group P-1 with a = 5.9395(15) Å, b = 11.471(3) Å, c = 11.901(3) Å, α = 70.075(4)°, β = 83.454(4)°, γ = 78.016(4)°, V = 744.9(3) Å3, Z = 2 cell parameters. This work is aimed to study the weak interactions in the crystal packing of a new synthesized oxadiazine derivate. The contributions of the most important intermolecular interactions in the crystal structure were investigated by 3D-Hirshfeld surface (HS) and 2D-fingerprint analysis. The C[sbnd]H···O interactions as the most important contributors to the crystal packing between the oxygen of the oxadiazine ring and the hydrogen atom of phenyl ring appear as bright red spots visible on the HS surface. The hydrogen-bonded interaction of MPMP-OXA has been investigated using noncovalent interactions approach. The molecular docking studies for the synthesized compound were performed to gain insight into the inhibition nature of this molecule against DNA Gyrase B Candida and 3-chymotrypsin-like protease (SARS-CoV main protease) proteins and resulted in good activities for new anti-agents. Lastly, Bioavailability, druggability as well as absorption, distribution, metabolism, excretion, and toxicity parameters (ADMET), and gastrointestinal absorption (BOILED-Egg method) properties of newly synthesized compound using smile codes were performed in detail. © 2023 Elsevier B.V.

Double-Network Protein Hydrogels as Flexible Pressure Sensors for Contactless Delivery

To meet the growing demand for sustainable development and ecofriendliness, hydrogels based on biopolymers have attracted widespread attention for developing flexible pressure sensors. Natural globular proteins exhibit great potential for developing biobased pressure sensors owing to their advantages of high water solubility, easy gelation, biocompatibility, and low production cost. However, realizing globular protein hydrogel-based sensors with interfacial and bulk toughness for pressure sensing and use in wearable devices remains a challenge. This study focuses on developing a high-performance flexible pressure sensor based on a biobased protein hydrogel. Consequently, a flexible protein/polyacrylamide (PAM) hydrogel with a featured double-network (DN) structure linked covalently with hydrogen bonds was first synthesized via a one-pot method based on natural ovalbumin (OVA). The unique DN structure of the as-synthesized OVA/PAM hydrogel affords excellent mechanical performance, flexibility, and adhesion properties. The mechanical properties of the DN hydrogel were enhanced after further cross-linking with Fe3+ and treatment with glycerol. Subsequently, the flexible pressure sensor was constructed by sandwiching a microstructured OVA/PAM dielectric layer between two flexible silver nanowire electrodes. The obtained sensor exhibits a high sensitivity of 2.9 kPa-1 and a short response time of 18 ms, ensuring the ability to monitor physiological signals. Based on its excellent performance, the fabricated sensor was used for monitoring the signals obtained using practical applications such as wrist bending, finger knocking, stretching, international Morse code, and pressure distribution. Particularly, we implemented a contactless delivery system using the fabricated OVA-based pressure sensors linked to unmanned vehicles and global positioning systems, providing a solution for low-risk commodity distribution during Coronavirus disease 2019 (COVID-19). © 2023 American Chemical Society.

Evaluation of the black soybean hulls agro-industrial waste for chloroquine removal from aqueous medium and treatment of multi-components

The COVID-19 pandemic increased the pollution of water resources by some contaminants, e.g., chloroquine (CQN), due to its probable benefit in the treatment of the virus. Thus, is necessary the removal of CQN from water through advanced techniques. Black soybeans have been widely used due to their benefits to human health, and as a result, there was an increase in soybean husk residue, the main by-product of the soybean processing industry. Given the current scenario and the need to develop new uses for this agricultural residue, this study aimed to establish an economical and environmental biotechnology by the CQN adsorption process onto black soybean hulls (BSH) for the first time. BSH was characterized by physicochemical and spectroscopic techniques that demonstrated porosity, organic functional groups and negative surface charges. The pH study did not affect CQN adsorption pronouncedly, indicating that π-interactions and hydrogen bonds are the main mechanisms of the adsorption process. The maximum adsorption capacity was 75.06 ± 2.24 mg g−1 with 240 min of contact time at 288 K. In order to verify the biosorbent applicability, the safranin orange dye and triclosan adsorption were also evaluated onto BSH. The absorption peaks of the contaminants used in the synthetic mixture demonstrated a removal rate of 90.81 ± 0.80% for safranin orange, 66.79 ± 1.12% for triclosan and 70.62 ± 0.67% for CQN. The satisfactory removal of other contaminants indicates that BSH is a promising, affordable and environmentally friendly biosorbent with applicability potential for alternative treatment of contaminated water. © 2023 Taylor & Francis Group, LLC.

Molecular docking analysis of novel quercetin derivatives for combating SARS-CoV-2

Quercetin belongs to the flavonoid family, which is one of the most frequent types of plant phenolics. This flavonoid compound is a natural substance having a number of pharmacological effects, including anticancer and antioxidant capabilities, as well as being a strong inhibitor of various toxicologically important enzymes. We discuss the potential of newly recently synthesized quercetin-based derivatives to inhibit SARS-CoV-2 protein. ADMET analysis indicated that all of the studied compounds had low toxicities and good absorption and solubility properties. The molecular docking results revealed that the propensity for binding to SARS-CoV-2 main protease is extraordinary. The results are remarkable not only for the binding energy values, which outperform several compounds in prior studies, but also for the number of hydrogen bonds formed. Compound 7a was capable of forming 10 strong hydrogen bonds as well as interact to the protein receptor with a binding energy of -7.79 kcal/mol. Therefore, these compounds should be highlighted in further experimental studies in the context of treating SARS-CoV-2 infection and its effects.

All-atom simulations of the trimeric spike protein of SARS-CoV-2 in aqueous medium: Nature of interactions, conformational stability and free energy diagrams for conformational transition of the protein.

The spike protein of SARS-CoV-2 exists in two major conformational states, namely the 'open' and 'closed' states which are also known as the 'up' and 'down' states, respectively. In its open state, the receptor binding domain (RBD) of the protein is exposed for binding with ACE2, whereas the spike RBD is inaccessible to ACE2 in the closed state of the protein. In the current work, we have performed all-atom microsecond simulations of the full-length trimeric spike protein solvated in explicit aqueous medium with an average system size of ~0.7 million atoms to understand the molecular nature of intra- and inter-chain interactions, water-bridged interactions between different residues that contribute to the stability of the open and closed states of the protein, and also the free energy landscape for transition between the open and closed states of the protein. We have also examined the changes of such interactions that are associated with switching from one state to the other through both unbiased and biased simulations at all-atom level with total run length of 4 µs. Interestingly, after about 0.8 µs of unbiased molecular dynamics run of the spike system in the open state, we observed a gradual transition of the monomeric chain (B) from open to its partially closed or down state. Initially the residues at the interface of chain B RBD in the open state spike protein were at non-hydrogen-bonding distances from the residues of chain C RBD. However, the two RBDs gradually came closer and finally the residue S459 of the RBD of chain B made a hydrogen bond with F374 of chain C in the last 200 ns of the simulation along with formation of a few more hydrogen bonds involving other residues. Since no transition from closed to the open state of the protein is observed in the present 1 µs unbiased simulation of the closed state protein, the current study seems to suggest that the closed conformational state is preferred for the spike protein of SARS-CoV-2 in aqueous medium. Furthermore, calculations of the free energy surface of the conformational transition from open (up) to the closed (down) state using a biased simulation method reveal a free energy barrier of ~3.20 kcal/mol for the transition of RBD from open to the closed state, whereas the barrier for the reverse process is found to be significantly higher.

Assessment of relationship between aging and contaminant-carryover for different filter layer of surgical mask under urban environmental stressors

Abundant disposable surgical masks (SMs) remain in the environment and continue to age under urban environmental stressors. This study aimed to investigate the aging characteristics of SMs and the effect of different aged layers of SMs on phenanthrene (PHE), tylosin (TYL), and sulfamethazine (SMT) under two different urban environmental stressors (UV and ozone). The results show that UV exposure causes more severe aging of the SM layers than ozone. The middle layer, made of melt-brown fabric, has displayed the highest degree of aging due to its smaller diameter and mechanical strength. The two-dimensional correlation spectroscopy (2D-COS) analysis reveals the different aging sequences of functional groups and three layers in aged SMs under the two urban environmental stressors. Whether the SMs are aged or not, the adsorptions of three organic pollutants on SMs are positively correlated with the octanol-water partition coefficient. Furthermore, except for the dominant hydrophobic interaction, aged SMs can promote the adsorption of three organic pollutants by accessory interactions (hydrogen bonding and partition), depending on their structures. These findings highlight the environmental effects of new microplastic (MP) sources and coexisting pollutants under the influence of COVID-19, which is helpful in accurately evaluating the biological toxicity of SMs. © 2022 Elsevier B.V.

Virtual screening of sulfur compounds of Allium against coronavirus proteases: E-Ajoene is a potential dual protease targeting covalent inhibitor

Mitigation of the activity of the main protease (Mpro) and papain-like protease (PLpro) of SARS CoV-2 has direct implications in combating the ongoing deadly COVID-19 pandemic. The active site of these proteases contains cysteine thiols which are covalently modified by the sulfur drugs such as ebselen and disulfiram. The natural product of Allium contains several reactive sulfur compounds that may covalently modify the active site cysteine thiols of coronavirus proteases. The report has assessed the binding affinity of the 52 different sulfur compounds of Allium against both Mpro and PLpro of coronavirus by conventional docking methods. Three of the top six compounds have demonstrated high affinity for both the proteases, namely, E-ajoene (S3), S-(3-pentanyl)-L-cysteine-sulfoxide (S49), and 1-propenyl allyl thiosulfinate (S14). The reactive sulfur compounds E-ajoene and 1-propenyl allyl thiosulfinate were subjected to the calculation of energetics of the putative reactions and covalent docking studies. The results indicate they covalently modify the active site cysteine thiols of the proteases through S-thioallylation, S-thioallyl sulfinyl propenylation, and S-thiopropenylation. The diversity of covalent modifications, high affinity for both the proteases and sulfur-mediated hydrogen bonds at the active site indicate that E-ajoene is a potential dual protease targeting covalent inhibitor of SARS CoV-2.

Electrospray-on-Electrospun Breathable, Biodegradable, and Robust Nanofibrous Membranes with Photocatalytic Bactericidal Activity

The increasing emergence of infectious diseases like COVID-19 has created an urgent need for filtration/purification materials coupled with multifunctional features such as mechanical integrity, excellent airflow/filtration, and antibacterial/antimicrobial properties. Polymer membranes and metal-organic frameworks (MOFs) have demonstrated high effectiveness in air filtration and purification. MOF nanoparticles have been introduced into electrospun polymer nanofibrous membranes through embedding or postsolution growth. However, the derived hybrids are still facing the issue of (1) limited MOF exposure, which leads to low efficacy;and (2) uncontrollable growth, which leads to pore blocking and low breathability. In this work, we customized an electrospray-on-electrospinning in situ process to dynamically integrate MOF nanoparticles into a robust and elastic continuous nanofibrous membrane for advanced properties including high mechanical strength and flexibility, excellent breathability, particle filtration, and good antimicrobial performance. Biodegradable polylactic acid was reinforced by the poly(hydroxybutyrate)-di-poly(DLA-CL)x copolymer (PHBR) and used as an electrospinning matrix, while MOF nanoparticles were simultaneously electrically sprayed onto the nanofibers with easily controllable MOF loading. The MOF nanoparticles were homogeneously deposited onto nanofibers without clogging the pores in the membrane. The collision of PLA and MOF under the wet status during electrospinning and the hydrogen bonding through C═O and N-H bonds strengthen the affinity between PLA nanofibers and MOF nanoparticles. Because of these factors, the MOF-incorporated PLA/PHBR nanofibrous membrane achieved over 95% particle filtration efficiency with enhanced mechanical properties while maintaining high breathability. Meanwhile, it exhibits excellent photocatalytic antibacterial performance, which is necessary to kill microbes. The electrospray-on-electrospinning in situ process provides an efficient and straightforward way to hybridize one-dimensional (1D) or two-dimensional (2D) nanomaterials into a continuous nanofibrous membrane with strong interaction and controllable loading. Upon integrating proper functionalities from the materials, the obtained hybrids are able to achieve multifunctionalities for various applications. © 2023 American Chemical Society.

Protein Crystallography: Achievements and Challenges

Proteins are the most important biological macromolecules, and are involved in almost all aspects of life. Therefore, the study of the structure of proteins is of great practical and fundamental importance. On the one hand, knowledge of the spatial structure is necessary to study the basic principles of protein functioning;for example, the mechanisms of enzymatic reactions. On the other hand, knowledge of the spatial structure of proteins is used, for example, in biotechnology, for the design of enzymes with desired properties, as well as in drug design. Today, the main method for determining the spatial structure of a protein is X-ray structural analysis of protein crystals. The main difficulty in applying this method is in obtaining a perfect protein-crystal. This review is devoted to the successes and challenges of modern protein crystallography.

Infrared Spectroscopy Study on Temperature Characteristics of Several Common Antibiotics and Therapeutic COVID-19 Drugs

The far infrared (1~10 THz) and mid-infrared (400~4 000 cm-1) spectra of six common antibiotics (Ofloxacin capsules, Ofloxacin tablets, Norfloxacin capsules, Azithromycin tablets, Roxithromycin tablets and Levofloxacin hydrochloride tablets), three antiviral drugs for COVID-19 (Ribavirin tablets, Abidol hydrochloride tablets and Chloroquine phosphate tablets) and an expectorant drug (Ambroxol hydrochloride tablets) within shelf-life were studied. The effects of vehicles and another high temperature environment (65 ℃) on the structure and crystal form of drugs were simulated and fed back to the changes in infrared spectra. After two months of continuous experiments, it was found that the structure and crystal form of other drugs had hardly changed except in ambroxol hydrochloride tablets. When capsule drugs were placed in high-temperature environment for a long time, the epidermis would become brittle and easy to rupture, but the efficacy of internal drugs had hardly changed. Taking fluoroquinolone antibiotics (Ofloxacin and Norfloxacin) as examples, combined with density functional theory (DFT) and the potential energy distribution (PED) method, the theoretical infrared spectra of the two antibiotics monomers, polymers and crystals were calculated by Crystal 14 and Gaussian 16 software with B3LYP/6-311++G(d,p) basis set. The vibrational modes and their contribution rates corresponding to all characteristic peaks were obtained, and the experimental spectrum was accurately identified. It was also found that from monomer to polymer and then to crystal, the stacking force (π-π interaction) between lattices accounted for the largest proportion of inter-molecular interaction, more than 90%. Therefore, the theoretical calculation was more consistent with the experimental results only when the crystal with periodic boundary conditions was taken as the initial configuration. The vibrational modes in the far infrared band mainly came from the collective vibration of molecules (vibration accounts for more than 99%, rotation and translation account for less than 1%), and the out-of-plane bending caused by inter-molecular hydrogen bond and Van der Waals force contributes the most, more than 90%. In the mid-infrared band, there were also a certain proportion of inter-molecular interactions. For example, the peaks of norfloxacin at 1 440 cm-1 and ofloxacin at 1 524 cm-1 can only be reproduced in the theoretical spectrum with the crystal as the configuration, respectively, from the collective vibration and the stretching of O-H…O bonds. © 2022 Science Press. All rights reserved.

Multi-ligand molecular docking, simulation, free energy calculations and wavelet analysis of the synergistic effects between natural compounds baicalein and cubebin for the inhibition of the main protease of SARS-CoV-2.

Combination drugs have been used for several diseases for many years since they produce better therapeutic effects. However, it is still a challenge to discover candidates to form a combination drug. This study aimed to investigate whether using a comprehensive in silico approach to identify novel combination drugs from a Chinese herbal formula is an appropriate and creative strategy. We, therefore, used Toujie Quwen Granules for the main protease (Mpro) of SARS-CoV-2 as an example. We first used molecular docking to identify molecular components of the formula which may inhibit Mpro. Baicalein (HQA004) is the most favorable inhibitory ligand. We also identified a ligand from the other component, cubebin (CHA008), which may act to support the proposed HQA004 inhibitor. Molecular dynamics simulations were then performed to further elucidate the possible mechanism of inhibition by HQA004 and synergistic bioactivity conferred by CHA008. HQA004 bound strongly at the active site and that CHA008 enhanced the contacts between HQA004 and Mpro. However, CHA008 also dynamically interacted at multiple sites, and continued to enhance the stability of HQA004 despite diffusion to a distant site. We proposed that HQA004 acted as a possible inhibitor, and CHA008 served to enhance its effects via allosteric effects at two sites. Additionally, our novel wavelet analysis showed that as a result of CHA008 binding, the dynamics and structure of Mpro were observed to have more subtle changes, demonstrating that the inter-residue contacts within Mpro were disrupted by the synergistic ligand. This work highlighted the molecular mechanism of synergistic effects between different herbs as a result of allosteric crosstalk between two ligands at a protein target, as well as revealed that using the multi-ligand molecular docking, simulation, free energy calculations and wavelet analysis to discover novel combination drugs from a Chinese herbal remedy is an innovative pathway.