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The recent emergence of novel coronavirus (SARS-CoV-2) has been a major threat to human society, as the challenge of finding suitable drug or vaccine is not met till date. With increasing morbidity and mortality, the need for novel drug candidates is under great demand. The investigations are progressing towards COVID-19 therapeutics. Among the various strategies employed, the use of repurposed drugs is competing along with novel drug inventions. Based on the therapeutic significance, the chemical constituents from the extract of Tinospora cordifolia belonging to various classes like alkaloids, lignans, steroids and terpenoids are investigated as potential drug candidates for COVID-19. The inhibition potential of the proposed compounds against viral spike protein and human receptor ACE2 were evaluated by computational molecular modeling (Auto dock), along with their ADME/ T properties. Prior to docking, the initial geometry of the compounds were optimized by Density functional theory (DFT) method employing B3LYP hybrid functional and 6-311 ? ? G (d,p) basis set. The results of molecular docking and ADME/T studies have revealed 6 constituents as potential drug candidates that can inhibit the binding of SARS-CoV-2 spike protein with the human receptor ACE2 protein. The narrowed down list of constituents from Tinospora cordifolia paved way for further tuning their ability to inhibit COVID-19 by modifying the chemical structures and by employing computational geometry optimization and docking methods.

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An in vitro antidiabetic activity on α-amylase and α–glucosidase activity of novel 10-chloro-4-(2-chlorophenyl)-12-phenyl-5,6-dihydropyrimido[4,5-a]acridin-2-amines (3a–3f) were evaluated. Structures of the synthesized molecules were studied by FT-IR, 1H NMR, 13C NMR, EI-MS, and single crystal X-ray structural analysis data. An in silico molecular docking was performed on synthesized molecules (3a–3f). Overall studies indicate that compound 3e is a promising compound leading to the development of selective inhibition of α-amylase and α-glucosidase.

On treatment of copper(II) acetate with aryl hydrazone ligands, four new solid derivatives of copper(II) were produced in appreciable yields. Various characterization techniques including infrared, UV–visible, NMR, electron paramagnetic resonance and mass spectroscopies, elemental analysis, scanning electron microscopy, powder X‐ray diffraction and thermogravimetric analysis revealed a tetra‐coordination in all the mononuclear crystalline complexes with high thermal stability. Further, significant interaction of these novel complexes with calf thymus DNA via intercalative mode of binding was revealed by electronic absorption spectroscopy. The chemical nuclease activity of the complexes on pBR322 DNA was investigated in the presence and absence of oxidizing agent (H2O2). A potent nuclease activity was observed only in the presence of H2O2. Further, antibacterial and antifungal studies of the new ligands and complexes revealed that the latter possessed comparatively better activity.

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Human immunodeficiency virus type 1 protease is essential for virus replication and maturation and has been considered as one of the important drug target for the antiretroviral treatment of HIV infection. The majority of HIV infections are caused due to non-B subtypes in developing countries. Subtype AE is spreading rapidly and infecting huge population worldwide. Understanding the interdependence of active and non-active site mutations in conferring drug resistance is crucial for the development effective inhibitors in subtype AE protease. In this work we have investigated the mechanism of resistance against indinavir due to therapy selected active site mutation V82F, non-active site mutations PF82V and their cooperative effects PV82F in subtype AE-protease using molecular dynamics simulations and binding free energy calculations. The simulations suggested all the three complexes lead to decrease in binding affinity of indinavir, whereas the PF82V complex resulted in an enhanced binding affinity compared to V82F and PV82F complexes. Large positional deviation of indinavir was observed in V82F complex. The preservation of hydrogen bonds of indinavir with active site Asp25/Asp25' and flap residue Ile50/50' via a water molecule is crucial for effective binding. Owing to the close contact of 80s loop with Ile50' and Asp25, the alteration between residues Thr80 and Val82, further induces conformational change thereby resulting in loss of interactions between indinavir and the residues in the active site cavity, leading to drug resistance. Our present study shed light on the effect of active, non-active site mutations and their cooperative effects in AE protease.