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•Treatment for moderately ill COVID-19 patients might arise from drug repurposing•RdRp, spike protein, and Mpro are relevant SARS-CoV-2 molecular targets.•Targeting human furin may ...contain viral infection and inflammation.•Molecular docking and clinical experience is useful for drug repurposing.
Several clinical trials to treat Coronavirus 2019 (COVID-19) are in progress around the world. Some of them rely on clinical experience, whereas others include computational predictions. Here, we provide an overview of current efforts in the search for COVID-19 therapies, focusing on structural information of relevant targets. We elaborate on a robust pharmacological rationale for the repurposing of existing drugs, highlighting key advantages of dual therapies with antiviral and anti-inflammatory activity. Furthermore, we provide a consensus list of molecules that could undergo preliminary randomized clinical trials against COVID-19.
Two Multi-particle collision dynamics algorithms that simulate nematic liquid crystals are generalised to reproduce active behaviour. One of the algorithms is due to Shendruk and Yeomans and is based ...on particles that carry an orientation vector ordered by a mean-field energy T. N. Shendruk and J. M. Yeomans,
Soft Matter
, 2015,
11
, 5101. In the other algorithm, due to Mandal and Mazza, particles possess an order parameter tensor which evolves according to the Qian-Sheng model of nematohydrodynamics S. Mandal and M. G. Mazza,
Phys. Rev. E
, 2019,
99
, 063319. For both methods activity is incorporated through a force proportional to the divergence of the local average order parameter tensor. Both implementations produce disclination curves in the nematic fluid that undergo nucleation and self-annihilation dynamics. Topological defects are found to be consistent with those observed in recent experiments of three-dimensional active nematics. Results permit to compare the length-scales over which the different nematic Multi-particle collision dynamics methods operate. The structure and dynamics of the orientation and flow fields agree with those obtained recently in numerical studies of continuum three-dimensional active nematics. Overall, our results open the opportunity to use mesoscopic particle-based approaches to study active liquid crystals in situations such as nonequilibrium states driven by flow or colloidal particles in active anisotropic solvents.
Multi-particle collision dynamics simulations based on mean-field interactions, conservation laws, and nematohydrodynamics are extended to active nematic liquid crystals to produce consistent dynamic topological structures and fields of orientation and flow.
The cyclopropane ring-opening reaction of riolozatrione, a natural product obtained from Jatropha dioica, afforded a 2,2-disubstituted 1,3-cyclohexandione displaying an alkyl methyl ether group at ...position 5. The conformational analysis of this product showed a high preference for the trans-diaxial conformation in both solution and solid state. Such conformation was possible from the noncovalent intramolecular nX → π*CO interactions (X = an element having an unshared electron pair), allowing the determination of the interaction energies. Since the nX → π*CO interactions can be regarded as additive, the energy values ranged from 4.52 to 6.51 kcal mol–1 for each carbonyl group with a strong dependency on the interatomic distances. The rigorous analysis of the electron density in the topological theory of atoms in molecules framework clearly shows that the origin of O–CO interactions are through the nO → π*CO electron transfer mechanism. Such interactions are slightly weaker than a canonical hydrogen bond but seemingly stronger than a van der Waals interaction. This interaction must be considered as a stereoelectronic effect due the electronic transfer between the interacting groups, which are limited by their relative stereochemistry and can be represented by a bond–no bond interaction, causing the pyramidalization of the carbonyl, which is the charge acceptor group.
We investigate numerically the motion of active elongated colloidal particles in a nematic liquid crystal. Active particles imposing three different anchoring conditions on the orientation field of ...the solvent are considered: homeotropic, planar, and Janus, which combine both homeotropic and planar conditions at different proportions. Active forces are parallel to the main symmetry axis of the colloidal particles. Our numerical approach sustains topological defects, thermal fluctuations and nematohydrodynamic flow. It is shown that the direction of motion of the active particles is determined by anchoring conditions. Transportation of active colloids with planar (homeotropic) anchoring occurs mainly parallel (perpendicular) to the nematic director field, whereas Janus particles exhibit an intermediate propagation direction. Results apply for active motion at low Reynolds and Ericksen numbers, where distortions on defects surrounding active particles are small.
•Multi-particle Collision Dynamics simulates colloidal particles with different anchoring conditions in nematic liquid crystals.•Anisotropic Janus particles in liquid crystals equilibrate at oblique angles with the nematic director.•Trajectories of active particles in liquid crystals can be tuned by anchoring conditions.
The noncovalent dyad of tetraphenylporphine and C
60
fullerene (H
2
TPP C
60
) and the tetraphenylporphine dimer (H
2
TPP H
2
TPP) were studied by density functional theory (DFT), using functionals ...that incorporate empirical dispersion correction (DFT-D), functionals that use a long-range correction (LC) scheme, a hybrid functional (B3LYP) and a highly parametrized empirical exchange-correlation functional (M05-2X). The results were compared to X-ray structures and interaction energies reported in previous experimental and theoretical studies. It was found that B3LYP and CAM-B3LYP functionals fail to reproduce the X-ray structures and binding energies of the TPP C
60
system. DFT-D functionals overestimated the π π energy interactions for both systems, however, the optimized structures agree well with those observed experimentally. The LC-BLYP functional predicts geometries similar to X-ray structures; nevertheless, due to the lack of correction in the dispersion energy, the predicted energies for both model systems are low. On the other hand, the M05-2X functional exhibited the best performance. Both the structures and binding energies calculated with M05-2X are consistent with experimental and theoretical evidence reported by other authors, as well as with our experimental results obtained by means of atomic force microscopy on H
2
TPP thin films grown on the HOPG/C
60
substrate by physical vapor deposition.
The exceptional ability of M05-2X/6-31G(d,p) calculations to describe binding energies and separation distances in porphyrin-fullerene complexes.
The noncovalent dyad of tetraphenylporphine and C
60
fullerene (H
2
TPP⋯C
60
) and the tetraphenylporphine dimer (H
2
TPP⋯H
2
TPP) were studied by density functional theory (DFT), using functionals ...that incorporate empirical dispersion correction (DFT-D), functionals that use a long-range correction (LC) scheme, a hybrid functional (B3LYP) and a highly parametrized empirical exchange–correlation functional (M05-2X). The results were compared to X-ray structures and interaction energies reported in previous experimental and theoretical studies. It was found that B3LYP and CAM-B3LYP functionals fail to reproduce the X-ray structures and binding energies of the TPP⋯C
60
system. DFT-D functionals overestimated the π⋯π energy interactions for both systems, however, the optimized structures agree well with those observed experimentally. The LC-BLYP functional predicts geometries similar to X-ray structures; nevertheless, due to the lack of correction in the dispersion energy, the predicted energies for both model systems are low. On the other hand, the M05-2X functional exhibited the best performance. Both the structures and binding energies calculated with M05-2X are consistent with experimental and theoretical evidence reported by other authors, as well as with our experimental results obtained by means of atomic force microscopy on H
2
TPP thin films grown on the HOPG/C
60
substrate by physical vapor deposition.
The noncovalent dyad of tetraphenylporphine and C sub(60) fullerene (H sub(2)TPP...C sub(60)) and the tetraphenylporphine dimer (H sub(2)TPP...H sub(2)TPP) were studied by density functional theory ...(DFT), using functionals that incorporate empirical dispersion correction (DFT-D), functionals that use a long-range correction (LC) scheme, a hybrid functional (B3LYP) and a highly parametrized empirical exchange-correlation functional (M05-2X). The results were compared to X-ray structures and interaction energies reported in previous experimental and theoretical studies. It was found that B3LYP and CAM-B3LYP functionals fail to reproduce the X-ray structures and binding energies of the TPP...C sub(60) system. DFT-D functionals overestimated the pi ... pi energy interactions for both systems, however, the optimized structures agree well with those observed experimentally. The LC-BLYP functional predicts geometries similar to X-ray structures; nevertheless, due to the lack of correction in the dispersion energy, the predicted energies for both model systems are low. On the other hand, the M05-2X functional exhibited the best performance. Both the structures and binding energies calculated with M05-2X are consistent with experimental and theoretical evidence reported by other authors, as well as with our experimental results obtained by means of atomic force microscopy on H sub(2)TPP thin films grown on the HOPG/C sub(60) substrate by physical vapor deposition.
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