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The Non-Structural protein 1 (NS1) of the Dengue virus is a crucial viral protein that plays a key role in host evasion and viral replication. The present study explores the pathophysiology of the host during the interaction with the viral protein via computational methods like protein–protein docking, virtual screening, and molecular dynamic simulation. Therefore, in this study we have focused on Dengue NS1 and the Human RPL18, to explore the binding mechanism and study their importance in viral proliferation. The results provided an insight into the vital amino acids of DENV NS1 (Gln_70 Glu_74 and Gly_161) which are responsible for viral-host interaction. The screening results showed that the Enamine_2436, NCI_99799, Malarial_19966, and FDA_54, had the strongest interaction with a docking score of −10.71, −8.11, −7.78, and −7.19 kcal/mol. In addition to the screening, the efficacy of the leads was validated through HOMO–LUMO studies. The Molecular dynamics simulation, PCA/FEL, and MMPBSA analysis showed that the Malarial_19966 maintained overall stability and binding affinity when compared to other leads. Hence the study comprehensively provides an insight into the biological phenomena of Dengue virus NS1 binding with Human RPL18 protein, along with possible inhibitors to suppress the Dengue viral translation and proliferation. [ABSTRACT FROM AUTHOR]

Coronavirus subverts the host cell cycle to create a favorable cellular environment that enhances viral replication in host cells. Previous studies have revealed that nucleocapsid (N) protein of the coronavirus porcine epidemic diarrhea virus (PEDV) interacts with p53 to induce cell cycle arrest in S-phase and promotes viral replication. However, the mechanism by which viral replication is increased in the PEDV N protein-induced S-phase arrested cells remains unknown. In the current study, the protein expression profiles of PEDV N protein-induced S-phase arrested Vero E6 cells and thymidine-induced S-phase arrested Vero E6 cells were characterized by tandem mass tag-labeled quantitative proteomic technology. The effect of differentially expressed proteins (DEPs) on PEDV replication was investigated. The results indicated that a total of 5709 proteins, including 20,560 peptides, were identified, of which 58 and 26 DEPs were identified in the PEDV N group and thymidine group, respectively (P

Numerous studies have shown that viruses can utilize or manipulate ribosomal proteins to achieve viral protein biosynthesis and replication. In our recent studies using proteomics analysis of virus-infected cells, we found that ribosomal protein L18 (RPL18) was the highest up-regulated differentially expressed protein, along with the increasingly expressed viral proteins later in Newcastle disease virus (NDV) infection. However, the association of RPL18 with viral protein biosynthesis and NDV replication remains unclear. In this study, we found that the expression and transcription levels of RPL18 was reduced early in NDV infection but increased later in NDV infection. In addition, the presence of cytoplasmic NDV matrix (M) protein was responsible for the increased expression of RPL18 in both virus-infected cells and plasmid-transfected cells. Moreover, cytoplasmic M protein increased RPL18 expression in a dose-dependent manner, even though they did not interact with each other. Furthermore, siRNA-mediated knockdown of RPL18 or overexpression of RPL18 dramatically reduced or enhanced NDV replication by decreasing or increasing viral protein translation rather than viral RNA synthesis and transcription. Taken together, these results suggested that the increased expression of RPL18 might be associated with the physical clumping together of the M protein, which in turn promoted viral protein biosynthesis and NDV replication. The increased expression of RPL18 is associated with the presence of cytoplasmic M protein. Cytoplasmic M protein increases RPL18 expression in a dose-dependent manner. Knockdown of RPL18 reduces NDV replication by decreasing viral protein translation. Overexpression of RPL18 enhances NDV replication by increasing viral protein translation. [ABSTRACT FROM AUTHOR]

Rice stripe virus (RSV) transmitted by the vector, small brown planthopper (SBPH), can cause a severe rice disease. The nucleocapsid (N) protein is the major component of RSV ribonucleoprotein particles (RNPs), and it plays important roles in viral persistent-propagative transmission by SBPH. To gain further insights into the vector components enabling RSV transmission, a GAL4-based yeast two-hybrid system was utilized to find unknown vector factors that interact with the N protein. Thirteen different proteins were identified as factors that interact with the N protein. The interaction between 60S ribosomal protein L18 (RPL18) and the N protein was further studied. Although the expression of RPL18 was not altered in insects during RSV infection, RPL18 was validated to bind directly to RSV RNPs and interact with RSV N protein. Knockdown of RPL18 dramatically reduced viral RNA and protein levels, especially viral protein expression, indicating a requirement for RPL18 in RSV translation and replication. Our results provide evidence that RPL18 is a critical factor required for RSV accumulation in SBPH, which suggests that the vector factor RPL18 may be as a potential target to develop for controlling the transmission of rice virus. [ABSTRACT FROM AUTHOR]

• The differentially expressed protein profiles of PEDV N-induced S-phase arrest cells were firstly characterized. • The ribosomal proteins were associated with viral replication increase in PEDV N-induced S-phase arrest cells. • The 60S ribosomal protein L18 could significantly enhance PEDV replication. Coronavirus subverts the host cell cycle to create a favorable cellular environment that enhances viral replication in host cells. Previous studies have revealed that nucleocapsid (N) protein of the coronavirus porcine epidemic diarrhea virus (PEDV) interacts with p53 to induce cell cycle arrest in S-phase and promotes viral replication. However, the mechanism by which viral replication is increased in the PEDV N protein-induced S-phase arrested cells remains unknown. In the current study, the protein expression profiles of PEDV N protein-induced S-phase arrested Vero E6 cells and thymidine-induced S-phase arrested Vero E6 cells were characterized by tandem mass tag-labeled quantitative proteomic technology. The effect of differentially expressed proteins (DEPs) on PEDV replication was investigated. The results indicated that a total of 5709 proteins, including 20,560 peptides, were identified, of which 58 and 26 DEPs were identified in the PEDV N group and thymidine group, respectively (P < 0.05; ratio ≥ 1.2 or ≤ 0.8). The unique DEPs identified in the PEDV N group were mainly involved in DNA replication, transcription, and protein synthesis, of which 60S ribosomal protein L18 (RPL18) exhibited significantly up-regulated expression in the PEDV N protein-induced S-phase arrested Vero E6/IPEC-J2 cells and PEDV-infected IPEC-J2 cells (P < 0.05). Further studies revealed that the RPL18 protein could significantly enhance PEDV replication (P < 0.05). Our findings reveal a mechanism regarding increased viral replication when the PEDV N protein-induced host cells are in S-phase arrest. These data also provide evidence that PEDV maintains its own replication by utilizing protein synthesis-associated ribosomal proteins. [ABSTRACT FROM AUTHOR]