THE MOLECULAR INTERACTION AND ADMET PREDICTION OF MODIFIED JPH203 AS A POTENTIAL RADIOPHARMACEUTICAL KIT FOR MOLECULAR IMAGING OF CANCER: AN IN SILICO RESEARCH

Objective: In this study, various types of pharmacokinetic modifying linkers and chelators are combined with JPH203 to obtain the best-docked molecule for prospective radiopharmaceutical kits. Methods: AutoDock 4.2.6 and AutoDockTools 1.5.6 programs was used to do the molecular docking simulation and ADMET prediction was done using VNN-ADMET to predict the pharmacokinetics and toxicity of the ligand. Results: The result of this study showed that JPH203-linker K-NOTA has the best affinity with a docking score of about-10.7 kcal/mol and shows hydrogen interaction with Tyr259, which acts as key residue of the active site. Conclusion: Based on the results, JPH203-linker K-NOTA has good potential as a radiopharmaceutical kit of cancer.

Dual-Crosslinked Oxidized Pectin/N-Succinyl Chitosan Hydrogel Containing Graphene Oxide Nanosheets for Tissue Engineering Application

Biopolymer-based hydrogels are commonly used in clinical applications. In the present study, N- succinyl chitosan (NSC), oxidized pectin (OP), and graphene oxide (GO) were used to develop a new dual-crosslinked hydrogel system. The dynamic OP/NSC/GO hydrogel showed quick gelation and great injectability due to the cooperation of hydrogen interaction between the GO nanosheets and the NSC and OP macromolecules and Schiff-based crosslinking by amino and aldehyde functional groups of polysaccharide derivatives. The performance of the above-mentioned hydrogel was improved when the GOs were embedded. When the GO content was 6 (mg/ml), the hydrogel showed the best overall performance, with a 10-minute healing time, a quick gelation time (~ 13s), acceptable swelling ability, suitable conductivity, great hemocompatibility, and strong biological compatibility. These results showed that the composite hydrogel could be used as a promising conductive injectable self-healing hydrogel for tissue engineering applications.

Possible Link between Higher Transmissibility of Alpha, Kappa and Delta Variants of SARS-CoV-2 and Increased Structural Stability of Its Spike Protein and hACE2 Affinity

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak in December 2019 has caused a global pandemic. The rapid mutation rate in the virus has created alarming situations worldwide and is being attributed to the false negativity in RT-PCR tests. It has also increased the chances of reinfection and immune escape. Recently various lineages namely, B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.617.3 have caused rapid infection around the globe. To understand the biophysical perspective, we have performed molecular dynamic simulations of four different spikes (receptor binding domain)-hACE2 complexes, namely wildtype (WT), Alpha variant (N501Y spike mutant), Kappa (L452R, E484Q) and Delta (L452R, T478K), and compared their dynamics, binding energy and molecular interactions. Our results show that mutation has caused significant increase in the binding energy between the spike and hACE2 in Alpha and Kappa variants. In the case of Kappa and Delta variants, the mutations at L452R, T478K and E484Q increased the stability and intra-chain interactions in the spike protein, which may change the interaction ability of neutralizing antibodies to these spike variants. Further, we found that the Alpha variant had increased hydrogen interaction with Lys353 of hACE2 and more binding affinity in comparison to WT. The current study provides the biophysical basis for understanding the molecular mechanism and rationale behind the increase in the transmissivity and infectivity of the mutants compared to wild-type SARS-CoV-2.

Hydrogen Atom and Molecule Adsorptions on FeCrAl (100) Surface: A First-Principle Study

FeCrAl alloys are promising accident-tolerant fuel (ATF) cladding materials for applications in light water reactors (LWRs). Despite the excellent mechanical and antioxidation properties, this series of iron-based alloys has poor hydrogen embrittlement (HE) resistance due to the strong hydrogen uptaking ability. The hydrogen embrittlement effect can cause the degradation and premature failure of the material, and this effect can be enhanced by the high-temperature/high-pressure/high-irradiation environment in reactors. So, the potential danger should be taken seriously. In this paper, we have studied the hydrogen atom and molecule adsorptions on both Fe (100) and FeCrAl (100) surfaces to discover how the hydrogen atom and molecule (H/H2) interact with the Fe and FeCrAl (100) surface in the first place. The results show that there are strong element effects on the FeCrAl surface. The Al atom itself has no interaction with hydrogen. When the Al atom is beside the Fe atom, this Fe atom has a slightly lower interaction with hydrogen. However, the Al atom beside the Cr atom will enhance the hydrogen interaction with this Cr atom. On the other hand, when the Cr atom is beside the Fe atom, these two atoms (Fe–Cr bridge site) can reduce the interactions with H. In addition, when two Cr and two Fe atoms together make a four-fold site (FF site), the two Cr atoms can increase the interaction of the two Fe atoms with H. The element effects discovered can be a good guide for making hydrogen prevention coatings.

Pharmacokinetic predictions and docking studies of substituted aryl amine-based triazolopyrimidine designed inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH)

Background The sixteen (16) designed data set of substituted aryl amine-based triazolopyrimidine were docked against Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) employing Molegro Virtual Docker (MVD) software and their pharmacokinetic property determined through SwissADME predictor. Results The docking studies shows compound D16, 5-((6-methoxy-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)amino)benzo[b]thiophen-4-ol to be the most interactive and stable derivative (re-rank score = − 114.205 kcal/mol) resulting from the hydrophobic as well as hydrogen interactions. The hydrogen interaction produced one hydrogen bond with the active residues LEU359 (H∙∙H∙∙O) at a bond distances of 2.2874 Å. All the designed derivatives were found to pass the Lipinski rule of five tests, supporting the drug-likeliness of the designed compounds. Conclusion The ADME analysis revealed a perfect concurrence with the Lipinski Ro5, where the derivatives were found to possess good pharmacokinetic properties such as molar refractivity (MR), number of rotatable bonds (nRotb), log of skin permeability (log Kp), blood-brain barrier (BBB). These results could a deciding factor for the optimization of novel antimalarial compounds.