In-Silico Molecular Docking and Pharmaco-Kinetic Activity Analysis of Potential Inhibitors against SARS-CoV-2 Spike Glycoproteins

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) is a causative agent of the potentially fatal coronavirus disease (COVID-19). Coronavirus targets the human respiratory system primarily. It can also infect the gastrointestinal, hepatic, and central nervous systems of humans, avians, bats, livestock, mice, and many other wild animals, as these are primary targets of the pathogen. This study aims to screen out the most potent inhibitor for SARS-CoV-2 (COVID-19) spike glycoproteins among the selected drugs, and computational tools have been utilized for this purpose. The selected drugs have been designed to explore their structural properties in this study by molecular orbital calculation. To inhibit the spike glycoproteins, the performance of these drugs was also examined by molecular docking calculation. In improving the performance of drugs, non-bond interactions play a significant role. To determine the chemical reactivity of all the medicines, HOMO and LUMO energy values were also calculated. The combined calculations exhibited that Ledipasvir among the selected drugs can be the most potent drug to treat SARS-CoV-2 compared to other medications.

QSAR and Ab Initio studies of quinolon-4(1H)-imine derivatives as antimalarial agents

Study on antimalarial activity of 22 quinolon-4(1H)-imine derivatives by using Quantitative Structure-Activity Relationships (QSAR) has been performed. Electronic and molecular descriptors were used in Quantitative Structure-Activity Relationships (QSAR) model and it was obtained from Hartree-Fock (HF) molecular orbital calculation with 6-31G basis set. QSAR analysis has been performed by multiple linear regression (MLR) method. The best equation of QSAR model on this study is: pEC50 = -4,177 + (37,902 x qC3) + (171,282 x qC8) + (9,061 x qC10) + (125,818 x qC11) + (-149,125 x qC17) + (191,623 x qC18), with statistical parameters, n = 22; r2 = 0,910; SEE = 0,171; Fcal/Ftab = 4,510 and PRESS = 0,697. The best equation can applied to design and predict new compounds with higher antimalarial activity.

Molecular Orbital Calculation of Lead-Free Perovskite Compounds for Efficient Use of Alkaline and Alkaline Earth Metals

The effective ionic charges of lead-free perovskite dielectric complex compounds were investigated with molecular orbital calculation. The base model was a double perovskite cluster that consisted of octahedral oxygen cages with a transition metal ion of titanium, niobium, or zirconium located at each of their centers, and alkali and/or alkaline earth metal ions located at the body center, corners, edge centers, or face centers of the cluster. The results showed significant covalent bonds between the transition metals and the oxygens, and the alkali metals, especially sodium and oxygen. On the other hand, the alkaline earth metals have weak covalency. Calculation was also performed with the replacement of some of the oxygens with chlorine or fluorine; such replacement enhances the covalency of the transition metals. These trends provide good guidelines for the design properties of lead-free perovskite piezoelectrics based on ubiquitous sodium use.

Intermolecular Interaction Among Remdesivir, RNA and RNA-Dependent RNA Polymerase of SARS-CoV-2 Analyzed by Fragment Molecular Orbital Calculation

<p>COVID-19, a disease caused by a new strain of coronavirus (SARS-CoV-2) originating from Wuhan, China, has now spread around the world, triggering a global pandemic, leaving the public eagerly awaiting the development of a specific medicine and vaccine. In response, aggressive efforts are underway around the world to overcome COVID-19. In this study, referencing the data published on the Protein Data Bank (PDB ID: 7BV2) on April 22, we conducted a detailed analysis of the interaction between the complex structures of the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 and Remdesivir, an antiviral drug, from the quantum chemical perspective based on the fragment molecular orbital (FMO) method. In addition to the hydrogen bonding and intra-strand stacking between complementary strands as seen in normal base pairs, Remdesivir bound to the terminus of an primer-RNA strand was further stabilized by diagonal π-π stacking with the -1A base of the complementary strand and an additional hydrogen bond with an intra-strand base, due to the effect of chemically modified functional group. Moreover, stable OH/π interaction is also formed with Thr687 of the RdRp. We quantitatively revealed the exhaustive interaction within the complex among Remdesivir, template-primer-RNA, RdRp and co-factors, and published the results in the FMODB database.</p>

Intermolecular Interaction Among Remdesivir, RNA and RNA-Dependent RNA Polymerase of SARS-CoV-2 Analyzed by Fragment Molecular Orbital Calculation

<p>COVID-19, a disease caused by a new strain of coronavirus (SARS-CoV-2) originating from Wuhan, China, has now spread around the world, triggering a global pandemic, leaving the public eagerly awaiting the development of a specific medicine and vaccine. In response, aggressive efforts are underway around the world to overcome COVID-19. In this study, referencing the data published on the Protein Data Bank (PDB ID: 7BV2) on April 22, we conducted a detailed analysis of the interaction between the complex structures of the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 and Remdesivir, an antiviral drug, from the quantum chemical perspective based on the fragment molecular orbital (FMO) method. In addition to the hydrogen bonding and intra-strand stacking between complementary strands as seen in normal base pairs, Remdesivir bound to the terminus of an primer-RNA strand was further stabilized by diagonal π-π stacking with the -1A base of the complementary strand and an additional hydrogen bond with an intra-strand base, due to the effect of chemically modified functional group. Moreover, stable OH/π interaction is also formed with Thr687 of the RdRp. We quantitatively revealed the exhaustive interaction within the complex among Remdesivir, template-primer-RNA, RdRp and co-factors, and published the results in the FMODB database.</p>