Phase Separation: "The Master Key" to Deciphering the Physiological and Pathological Functions of Cells.

Phase separation is a hot research field at present. It involves almost all aspects of cells and plays a significant role in cells, promising to be "a master key" in unlocking the mysteries of nature. In this review, the factors that affect phase separation are introduced, such as own component, electrostatic interaction, and chemical modification. Furthermore, the physiological roles of phase separation in cells, including molecules transport channel, gene expression and regulation, cellular division and differentiation, stress response, proteins refolding and degradation, cell connections, construction of skin barrier, and cell signals transmission, are highlighted. However, the disorder of phase separation leads to pathological condensates, which are associated with neurodegenerative diseases, tumors, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This relationship is considered the potential target for developing corresponded drugs and therapy. Some drugs targeting phase separation have improved meaningful, such as tankyrase, lipoamide, oligonucleotides, elvitagravir, nilotinib, CVL218, PJ34. All in all, mystery phase separation provides a new viewpoint for researchers to explore cells, and is expected to solve many unknown phenomena in nature.

SARS-CoV-2: The Monster Causes COVID-19

Coronaviruses are viruses whose particles look like crowns. SARS-CoV-2 is the seventh member of the human coronavirus family to cause COVID-19 which is regarded as a once-in-a-century pandemic worldwide. It holds has the characteristics of a pandemic, which has broy -55ught many serious negative impacts to human beings. It may take time for humans to fight the pandemic. In addition to humans, SARS-CoV-2 also infects animals such as cats. This review introduces the origins, structures, pathogenic mechanisms, characteristics of transmission, detection and diagnosis, evolution and variation of SARS-CoV-2. We summarized the clinical characteristics, the strategies for treatment and prevention of COVID-19, and analyzed the problems and challenges we face.

Non-RBM Mutations Impaired SARS-CoV-2 Spike Protein Regulated to the ACE2 Receptor Based on Molecular Dynamic Simulation.

The emergence of novel coronavirus mutants is a main factor behind the deterioration of the epidemic situation. Further studies into the pathogenicity of these mutants are thus urgently needed. Binding of the spinous protein receptor binding domain (RBD) of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptor was shown to initiate coronavirus entry into host cells and lead to their infection. The receptor-binding motif (RBM, 438-506) is a region that directly interacts with ACE2 receptor in the RBD and plays a crucial role in determining affinity. To unravel how mutations in the non-RBM regions impact the interaction between RBD and ACE2, we selected three non-RBM mutant systems (N354D, D364Y, and V367F) from the documented clinical cases, and the Q498A mutant system located in the RBM region served as the control. Molecular dynamics simulation was conducted on the mutant systems and the wild-type (WT) system, and verified experiments also performed. Non-RBM mutations have been shown not only to change conformation of the RBM region but also to significantly influence its hydrogen bonding and hydrophobic interactions. In particular, the D364Y and V367F systems showed a higher affinity for ACE2 owing to their electrostatic interactions and polar solvation energy changes. In addition, although the binding free energy at this point increased after the mutation of N354D, the conformation of the random coil (Pro384-Asp389) was looser than that of other systems, and the combined effect weakened the binding free energy between RBD and ACE2. Interestingly, we also found a random coil (Ala475-Gly485). This random coil is very sensitive to mutations, and both types of mutations increase the binding free energy of residues in this region. We found that the binding loop (Tyr495-Tyr505) in the RBD domain strongly binds to Lys353, an important residue of the ACE2 domain previously identified. The binding free energy of the non-RBM mutant group at the binding loop had positive and negative changes, and these changes were more obvious than that of the Q498A system. The results of this study elucidate the effect of non-RBM mutation on ACE2-RBD binding, and provide new insights for SARS-CoV-2 mutation research.