Outcomes of various clinical studies for the coronavirus disease 2019 (COVID-19) treatment indicated that the drug acts via inhibition of multiple pathways (targets) is likely to be more successful and promising. Keeping this hypothesis intact, the present study describes for the first-time, Grazoprevir, an FDA approved anti-viral drug primarily approved for Hepatitis C Virus (HCV), mediated multiple pathway control via synergistic inhibition of viral entry targeting host cell Angiotensin-Converting Enzyme 2 (ACE-2)/transmembrane serine protease 2 (TMPRSS2) and viral replication targeting RNA-dependent RNA polymerase (RdRP). Molecular modeling followed by in-depth structural analysis clearly demonstrated that Grazoprevir interacts with the key residues of these targets. Futher, Molecular Dynamics (MD) simulations showed stability and burial of key residues after the complex formation. Finally, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) analysis identified the governing force of drug-receptor interactions and stability. Thus, we believe that Grazoprevir could be an effective therapeutics for the treatment of the COVID-19 pandemic with a promise of unlikely drug resistance owing to multiple inhibitions of eukaryotic and viral proteins, thus warrants further clinical studies.

The review focuses on the tumor pyruvate kinase M2 (PKM2) modulators. Both activators and inhibitors developed against PKM2 are discussed.

Fluorenones are important constituents in material, medical and chemical sciences with potential applications in various domains. The key factors responsible for the diverse usage of fluorenones in material sciences are their intriguing and tunable photo, as well as physico‐chemical properties. Besides this, the presence of conjugated poly‐(en)ynes in the fluorenones makes them molecules of interest in material sciences. Fluorenones show various biological activities like antibiotics, anticancer, antiviral, and neuromodulatory, etc. Organic chemists are developing various protocols for the synthesis of fluorenones. Despite several protocols developed for their synthesis since 1931, there is no review covering their entire synthetic protocols. This review includes several classical and novel synthetic approaches for the synthesis of fluorenones. Furthermore, we delineated the mechanism by which they have been synthesized.

Discovery of novel and potent lead molecules for the specific therapeutic targets by de novo drug design is still in infancy. Here, we disclose the unprecedented development of imidazopyri(mi)dine-based tumor pyruvate kinase M2 (PKM2) modulators by subsequent link and grow strategy. The most potent modulator 15n acts as a PKM2 activator with an AC₅₀ of 90 nM, with considerable cancer cell-selectivity and membrane-permeability. NMR metabolomics studies also revealed that treatment with 15n results in diminution in lactate concentrations in MCF-7 cells. 15n binds to a previously reported site at PKM2 adjacent to the interface of two monomers. In molecular dynamics (MD) simulation studies, it was observed that 15n stabilizes the PKM2 at the dimeric interface, assisting in the formation of a biologically active tetramer conformation. 15n was also screened on MCF-7 breast cancer cell lines grown on 3-D scaffolds, and the results exhibited better anticancer potential compared to control, paving the way for future clinical studies.

Potassium tertiary butoxide (KO ^t Bu) mediated constructions of C–C, C–O, C–N, and C–S bonds are reviewed with special emphasis on their synthetic applications.