Human transcriptional coactivator PC4 is a highly abundant multifunctional protein which plays diverse important roles in cellular processes, including transcription, replication, and repair. It is also a unique activator of p53 function. Here we report that PC4 is a bona fide component of chromatin with distinct chromatin organization ability. PC4 is predominantly associated with the chromatin throughout the stages of cell cycle and is broadly distributed on the mitotic chromosome arms in a punctate manner except for the centromere. It selectively interacts with core histones H3 and H2B; this interaction is essential for PC4-mediated chromatin condensation, as demonstrated by micrococcal nuclease (MNase) accessibility assays, circular dichroism spectroscopy, and atomic force microscopy (AFM). The AFM images show that PC4 compacts the 100-kb reconstituted chromatin distinctly compared to the results seen with the linker histone H1. Silencing of PC4 expression in HeLa cells results in chromatin decompaction, as evidenced by the increase in MNase accessibility. Knocking down of PC4 up-regulates several genes, leading to the G2/M checkpoint arrest of cell cycle, which suggests its physiological role as a chromatin-compacting protein. These results establish PC4 as a new member of chromatin-associated protein family, which plays an important role in chromatin organization.

The recent emergence of the novel coronavirus (SARS-CoV-2) has raised global concern as it is declared a pandemic by the WHO. However, to date, there is no current regimen to mitigate the molecular pathogenesis of SARS-CoV-2 virus. Curcuminoids, bioactive ingredients present in Curcuma longa (turmeric), are known to exhibit diverse pharmacological properties. To the best of our understanding to date, SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for the host cellular entry. This is mediated via proteins of SARS-CoV-2, especially the spike glycoprotein receptor binding domain. Accordingly, our primary objective is to thwart virus replication and binding to the host system, leading us to probe curcuminoids efficiency towards key surface drug target proteins using the computational biology paradigm approach. Specifically, fourteen natural curcuminoids were studied for their possibility of inhibiting SARS-CoV-2. We studied their in silico properties towards SARS-CoV-2 target proteins by homology modelling, ADME, drug-likeness, toxicity predictions, docking molecular dynamics simulations and MM-PBSA free energy estimation. Among the curcuminoids docked to the receptor binding domain of SARS-CoV-2 spike glycoprotein, the keto and enol forms of curcumin form strong hydrogen bond interactions with ACE2 binding residues Q493, T501, Y505, Y489 and Q498. Molecular dynamics simulations, free energy binding and interaction energy validated the interaction and stability of the docked keto and enol forms of curcumin.