Molecular recognition has central role on the development of rational drug design. Binding affinity and interactions are two key components which aid to understand the molecular recognition in drug-receptor complex and crucial for structure-based drug design in medicinal chemistry. Herein, we report the binding affinity and the nonbonding interactions of azelaic acid and related compounds with the receptor DNA polymerase I (2KFN). Quantum mechanical calculation was employed to optimize the modified drugs using B3LYP/6-31G(d,p) level of theory. Charge distribution, dipole moment and thermodynamic properties such as electronic energy, enthalpy and free energy of these optimized drugs are also explored to evaluate how modifications impact the drug properties. Molecular docking calculation was performed to evaluate the binding affinity and nonbonding interactions between designed molecules and the receptor protein. We notice that all modified drugs are thermodynamically more stable and some of them are more chemically reactive than the unmodified drug. Promise in enhancing hydrogen bonds is found in case of fluorine-directed modifications as well as in the addition of trifluoroacetyl group. Fluorine participates in forming fluorine bonds and also stimulates alkyl, pi-alkyl interactions in some drugs. Designed drugs revealed increased binding affinity toward 2KFN. A1, A2 and A3 showed binding affinities of -8.7, -8.6 and -7.9 kcal/mol, respectively against 2KFN compared to the binding affinity -6.7 kcal/mol of the parent drug. Significant interactions observed between the drugs and Thr358 and Asp355 residues of 2KFN. Moreover, designed drugs demonstrated improved pharmacokinetic properties. This study disclosed that 9-octadecenoic acid and drugs containing trifluoroacetyl and trifluoromethyl groups are the best 2KFN inhibitors. Overall, these results can be useful for the design of new potential candidates against DNA polymerase I.

Paracetamol or acetaminophen is a medication commonly used in pain and fever. It is typically used for mild to moderate pain relief. It can produce selective inhibition to the prostaglandin synthesis. We envisage the density functional theory (DFT) with B3LYP/6-31G+(d,p) basis set to optimize the newly modified derivatives. Thermodynamic properties, molecular orbital features, dipole moment, atomic partial charge and electrostatic potential have been calculated in order to compare their physicochemical and biological properties. Molecular docking, nonbonding interactions, and dynamics simulation have been performed against prostaglandin H2 (PGH2) synthase protein 5F19 to investigate their binding affinity, binding modes, and stability of the protein-drug complex. ADMET prediction has been utilized to compare the absorption, metabolism, and carcinogenic properties of new derivatives with parent drug (PCT). From physicochemical data, all modified structures are thermodynamically stable; most of them are chemically more reactive and show better binding affinity than the parent drug. ADMET calculations predict the improved pharmacokinetic properties of modified derivatives. Based on physicochemical, docking, dynamics simulation and ADMET prediction results, this study can be helpful to design a new analgesic and antipyretic drug.

Cordycepin is a small molecule from medicinal mushroom Cordyceps, which has been reported for anticancer properties. In this study, we investigated cordycepin effect on cervical cancer cells in vitro. Results indicate that treatment of cordycepin controlled SiHa and Hela cervical cancer cell growth, increased the rate of their apoptosis, and interfered with cell cycle, specifically elongated S-phase. By using qPCR, we investigated the expression of anti-apoptotic and pro-apoptotic proteins as well as cell cycle protein's expression in mRNA levels, and found there was a downregulation of cell cycle proteins CDK-2, CYCLIN-A2 and CYCLIN-E1 by cordycepin treatment but no significant change in pro-apoptotic or anti-apoptotic proteins. The intracellular reactive oxygen species (ROS) level in cordycepin treated cells was increased significantly, implying that apoptosis might be induced by ROS. Western blot analysis confirmed significant decrease of Cdk-2 and mild decrease of Cyclin-E1 and Cyclin-A2 by cordycepin, which might be responsible for regulating cell cycle. Molecular docking simulation indicated high binding affinity of cordycepin against Cdk-2. Molecular dynamics simulation further confirmed that the docked pose of cordycepin-Cdk2 complex remained within the binding pocket for 10ns. Thus, our study suggests that cordycepin is effective against cervical cancer cells, and regulating cell cycle via cell cycle proteins, especially downregulating Cdk-2, and inducing apoptosis by generating ROS are among the mechanisms of anticancer activities of cordycepin.

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Background: SARS-CoV-2 is a coronavirus, of which infection causing COVID-19 was first reported in Wuhan, China at the end of 2019, and the outbreak became pandemic in February of 2020. Till now there is no effective drug or vaccine against this virus that can make complete cure; however, a number of drugs are in trials. Objectives: In this review, we have focused on an alternative therapeutic approach using natural products utilizing host anti-viral responses for resolving COVID-19 pathogenesis. Methods: We have searched databases like PubMed, Scopus, Web of Science and Google Scholar for articles related to natural products and viral diseases, with a specific focus on coronaviruses, as well as other RNA viruses and recent updates on COVID-19 pandemic, and collected articles and reviewed comprehensively. Results: Scientific studies clarified the viral pathogenesis that involved viral entrance into host cells, and antiviral response inside the cells, which can be effectively targeted by numerous natural compounds from different sources. Many of these compounds can potentially target viral genomic material or protein machinery. Natural products which were found effective against other coronaviruses, especially SARS-CoV or MERS-CoV (which emerged in 2002 and 2012, respectively) might be effective against SARS-CoV-2 due to their structural similarities; however, it needs time to establish the clinical success of these drugs. Conclusion: COVID-19 pandemic is a global emergency problem and urgent drug development is necessary. Natural products can be the biggest source of drugs, as they have been found effective in other coronaviruses previously; however, it needs time to establish these drugs for clinical application.

The exploration of alternative antimalarial therapeutics is a requisite for the emergence of resistance against Artemisinin. Considering the required cost and time length of classical small molecule drug discovery process, phytochemical screening of traditionally used medicinal plant which are repertoire of active compounds with antimalarial activity has become popular. To investigate the antimalarial property of traditionally used medicinal plants, a number of Erythrina spp have been reviewed systematically where less studied E. fusca has been selected for further analysis. Phytochemical investigation yielded five compounds namely; Phaseolin, Phytol, β-amyrin, Lupeol, and Stigmasterol. In-vitro antimalarial drug sensitivity HRP-II ELISA was carried out against chloroquine (CQ) sensitive 3D7 and CQ-resistant Dd2 strains. Extracts showed significant antimalarial activity against 3D7 and Dd2 strains (IC50 4.94 – 22 µg/mL) and these compounds have been reported here for the first time. Molecular docking analysis showed high binding energy (−9.0 ± 0.32 kcal/mole) indicating high degree of interaction between Phaseolin and 14 clinically important Plasmodium falciparum proteins at the active site. Stable interaction was also observed between ligand and protein from molecular dynamics simulation analysis with high free energy (−75.156 ± 11.459) that substantiates the potential of Phaseolin as an antimalarial drug candidate.