Archaeal SRP RNA and SRP19 facilitate the assembly of SRP54-FtsY targeting complex.

The signal recognition particle (SRP) plays an essential role in protein translocation across biological membranes. Stable complexation of two GTPases in the signal recognition particle (SRP) and its receptor (SR) control the delivery of nascent polypeptide to the membrane translocon. In archaea, protein targeting is mediated by the SRP54/SRP19/7S RNA ribonucleoprotein complex (SRP) and the FtsY protein (SR). In the present study, using fluorescence resonance energy transfer (FRET), we demonstrate that archaeal 7S RNA stabilizes the SRP54·FtsY targeting complex (TC). Moreover, we show that archaeal SRP19 further assists 7S RNA in stabilizing the targeting complex (TC). These results suggest that archaeal 7S RNA and SRP19 modulate the conformation of the targeting complex and thereby reinforce TC to execute protein translocation via concomitant GTP hydrolysis.

Protease Inhibitory Effect of Natural Polyphenolic Compounds on SARS-CoV-2: An In Silico Study.

The current pandemic, caused by SARS-CoV-2 virus, is a severe challenge for human health and the world economy. There is an urgent need for development of drugs that can manage this pandemic, as it has already infected 19 million people and led to the death of around 711,277 people worldwide. At this time, in-silico studies are providing lots of preliminary data about potential drugs, which can be a great help in further in-vitro and in-vivo studies. Here, we have selected three polyphenolic compounds, mangiferin, glucogallin, and phlorizin. These compounds are isolated from different natural sources but share structural similarities and have been reported for their antiviral activity. The objective of this study is to analyze and predict the anti-protease activity of these compounds on SARS-CoV-2main protease (Mpro) and TMPRSS2 protein. Both the viral protein and the host protein play an important role in the viral life cycle, such as post-translational modification and viral spike protein priming. This study has been performed by molecular docking of the compounds using PyRx with AutoDock Vina on the two aforementioned targets chosen for this study, i.e., SARS-CoV-2 Mpro and TMPRSS2. The compounds showed good binding affinity and are further analyzed by (Molecular dynamic) MD and Molecular Mechanics Poisson-Boltzmann Surface Area MM-PBSA study. The MD-simulation study has predicted that these natural compounds will have a great impact on the stabilization of the binding cavity of the Mpro of SARS-CoV-2. The predicted pharmacokinetic parameters also show that these compounds are expected to have good solubility and absorption properties. Further predictions for these compounds also showed no involvement in drug-drug interaction and no toxicity.

Investigating the role of Ebp1 in Chandipura virus infection.

ErbB-3 binding protein 1 (Ebp1) is a host protein which binds ErbB-3 receptor to induce signalling events for cell growth regulation. In addition, Ebp1 also interacts with ribonucleoprotein complexes. In recent times, Ebp1 was found to play an antagonistic role in viral infections caused by Influenza and Rinderpest viruses. In our present work we have tried to understand the role of Ebp1 in Chandipura virus (CHPV) infection. We have observed an induction in Ebp1 expression upon CHPV infection similar to other viruses. However, unlike other viruses an overexpressed Ebp1 only reduces viral protein expression, but does not affect its progeny formation. Additionally, this effect is being carried out in an indirect manner, as there is no interaction between Ebp1 and viral proteins. This is despite Ebp1's presence in viral inclusion bodies.

Astrakurkurone, a sesquiterpenoid from wild edible mushroom, targets liver cancer cells by modulating Bcl-2 family proteins.

Induction of apoptosis is the target of choice for modern chemotherapeutic treatment of cancer, where lack of potent "target-specific" drugs has led to extensive research on anticancer compounds from natural sources. In our study, we have used astrakurkurone, a triterpene isolated from wild edible mushroom, Astraeus hygrometricus. We have discussed the structure and stability of astrakurkurone employing single-crystal X-ray crystallography and studied its potential apoptogenicity in hepatocellular carcinoma (HCC) cells. Our experiments reveal that it is cytotoxic against the HCC cell lines (Hep 3B and Hep G2) at significantly low doses. Further investigations indicated that astrakurkurone acts by inducing apoptosis in the cells, disrupting mitochondrial membrane potential and inducing the expression of Bcl-2 family proteins, for example, Bax, and the downstream effector caspases 3 and 9. A molecular docking study also predicted direct interactions of the drug with antiapoptotic proteins Bcl-2 and Bcl-xL. Thus, astrakurkurone could become a valuable addition to the conventional repertoire of future anticancer drugs. © 2019 IUBMB Life, 1-11, 2019.

Network analysis reveals common host protein/s modulating pathogenesis of neurotropic viruses.

Network analysis through graph theory provides a quantitative approach to characterize specific proteins and their constituent assemblies that underlie host-pathogen interactions. In the present study, graph theory was used to analyze the interactome designed out of 50 differentially expressing proteins from proteomic analysis of Chandipura Virus (CHPV, Family: Rhabdoviridae) infected mouse brain tissue to identify the primary candidates for intervention. Using the measure of degree centrality, that quantifies the connectedness of a single protein within a milieu of several other interacting proteins, DJ-1 was selected for further molecular validation. To elucidate the generality of DJ-1's role in propagating infection its role was also monitored in another RNA virus, Japanese Encephalitis Virus (JEV, Family: Flaviviridae) infection. Concurrently, DJ-1 got over-expressed in response to reactive oxygen species (ROS) generation following viral infection which in the early phase of infection migrated to mitochondria to remove dysfunctional mitochondria through the process of mitophagy. DJ-1 was also observed to modulate the viral replication and interferon responses along with low-density lipoprotein (LDL) receptor expression in neurons. Collectively these evidences reveal a comprehensive role for DJ-1 in neurotropic virus infection in the brain.