Unearthing the role of septins in viral infections.

Septin proteins are a subfamily of closely related GTP-binding proteins conserved in all species except for higher plants and perform essential biological processes. Septins self-assemble into heptameric or octameric complexes and form higher-order structures such as filaments, rings, or gauzes by end-to-end binding. Their close association with cell membrane components makes them central in regulating critical cellular processes. Due to their organisation and properties, septins function as diffusion barriers and are integral in providing scaffolding to support the membrane's curvature and stability of its components. Septins are also involved in vesicle transport and exocytosis through the plasma membrane by co-localising with exocyst protein complexes. Recently, there have been emerging reports of several human and animal diseases linked to septins and abnormalities in their functions. Most of our understanding of the significance of septins during microbial diseases mainly pertains to their roles in bacterial infections but not viruses. This present review focuses on the known roles of septins in host-viral interactions as detailed by various studies.

Antiviral Activities of Streptomyces KSF 103 Methanolic Extracts against Dengue Virus Type-2.

Dengue has long been a serious health burden to the global community, especially for those living in the tropics. Despite the availability of vaccines, effective treatment for the infection is still needed and currently remains absent. In the present study, the antiviral properties of the Streptomyces sp. KSF 103 methanolic extract (Streptomyces KSF 103 ME), which consists of a number of potential antiviral compounds, were investigated against dengue virus serotype 2 (DENV-2). The effects of this extract against DENV-2 replication were determined using the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Findings from the study suggested that the Streptomyces KSF 103 ME showed maximum inhibitory properties toward the virus during the virus entry stage at concentrations of more than 12.5 µg/mL. Minimal antiviral activities were observed at other virus replication stages; adsorption (42% reduction at 50 µg/mL), post-adsorption (67.6% reduction at 50 µg/mL), prophylactic treatment (68.4% and 87.7% reductions at 50 µg/mL and 25 µg/mL, respectively), and direct virucidal assay (48% and 56.8% reductions at 50 µg/mL and 25 µg/mL, respectively). The Streptomyces KSF 103 ME inhibited dengue virus replication with a 50% inhibitory concentration (IC50) value of 20.3 µg/mL and an International System of Units (SI) value of 38.9. The Streptomyces KSF 103 ME showed potent antiviral properties against dengue virus (DENV) during the entry stage. Further studies will be needed to deduce the antiviral mechanisms of the Streptomyces KSF 103 ME against DENV.

Avian Influenza Virus Tropism in Humans.

An influenza pandemic happens when a novel influenza A virus is able to infect and transmit efficiently to a new, distinct host species. Although the exact timing of pandemics is uncertain, it is known that both viral and host factors play a role in their emergence. Species-specific interactions between the virus and the host cell determine the virus tropism, including binding and entering cells, replicating the viral RNA genome within the host cell nucleus, assembling, maturing and releasing the virus to neighboring cells, tissues or organs before transmitting it between individuals. The influenza A virus has a vast and antigenically varied reservoir. In wild aquatic birds, the infection is typically asymptomatic. Avian influenza virus (AIV) can cross into new species, and occasionally it can acquire the ability to transmit from human to human. A pandemic might occur if a new influenza virus acquires enough adaptive mutations to maintain transmission between people. This review highlights the key determinants AIV must achieve to initiate a human pandemic and describes how AIV mutates to establish tropism and stable human adaptation. Understanding the tropism of AIV may be crucial in preventing virus transmission in humans and may help the design of vaccines, antivirals and therapeutic agents against the virus.

The Putative Roles and Functions of Indel, Repetition and Duplication Events in Alphavirus Non-Structural Protein 3 Hypervariable Domain (nsP3 HVD) in Evolution, Viability and Re-Emergence.

Alphavirus non-structural proteins 1-4 (nsP1, nsP2, nsP3, and nsP4) are known to be crucial for alphavirus RNA replication and translation. To date, nsP3 has been demonstrated to mediate many virus-host protein-protein interactions in several fundamental alphavirus mechanisms, particularly during the early stages of replication. However, the molecular pathways and proteins networks underlying these mechanisms remain poorly described. This is due to the low genetic sequence homology of the nsP3 protein among the alphavirus species, especially at its 3' C-terminal domain, the hypervariable domain (HVD). Moreover, the nsP3 HVD is almost or completely intrinsically disordered and has a poor ability to form secondary structures. Evolution in the nsP3 HVD region allows the alphavirus to adapt to vertebrate and insect hosts. This review focuses on the putative roles and functions of indel, repetition, and duplication events that have occurred in the alphavirus nsP3 HVD, including characterization of the differences and their implications for specificity in the context of virus-host interactions in fundamental alphavirus mechanisms, which have thus directly facilitated the evolution, adaptation, viability, and re-emergence of these viruses.

Actinobacteria-a promising natural source of anti-biofilm agents

A biofilm is a community of microorganisms attached to a surface and embedded in a matrix of extracellular polymeric substances. Biofilms confer resistance towards conventional antibiotic treatments; thus, there is an urgent need for newer and more effective antimicrobial agents that can act against these biofilms. Due to this situation, various studies have been done to investigate the anti-biofilm effects of natural products including bioactive compounds extracted from microorganisms such as Actinobacteria. This review provides an insight into the anti-biofilm potential of Actinobacteria against various pathogenic bacteria, which hopefully provides useful information, guidance, and improvements for future antimicrobial studies. Nevertheless, further research on the anti-biofilm mechanisms and compound modifications to produce more potent anti-biofilm effects are required

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Actinobacteria-a promising natural source of anti-biofilm agents.

A biofilm is a community of microorganisms attached to a surface and embedded in a matrix of extracellular polymeric substances. Biofilms confer resistance towards conventional antibiotic treatments; thus, there is an urgent need for newer and more effective antimicrobial agents that can act against these biofilms. Due to this situation, various studies have been done to investigate the anti-biofilm effects of natural products including bioactive compounds extracted from microorganisms such as Actinobacteria. This review provides an insight into the anti-biofilm potential of Actinobacteria against various pathogenic bacteria, which hopefully provides useful information, guidance, and improvements for future antimicrobial studies. Nevertheless, further research on the anti-biofilm mechanisms and compound modifications to produce more potent anti-biofilm effects are required.

Interaction of Recombinant Gallus gallus SEPT5 and Brain Proteins of H5N1-Avian Influenza Virus-Infected Chickens.

Septin forms a conserved family of cytoskeletal guanosine triphosphate (GTP) binding proteins that have diverse roles in protein scaffolding, vesicle trafficking, and cytokinesis. The involvement of septins in infectious viral disease pathogenesis has been demonstrated by the upregulation of SEPT5 protein and its mRNA in brain tissues of H5N1-infected chickens, thus, providing evidence for the potential importance of this protein in the pathogenesis of neurovirulence caused by the avian influenza virus. In this study, cloning, expression, and purification of Gallus gallus SEPT5 protein was performed in Escherichia coli. The SEPT5 gene was inserted into the pRSETB expression vector, transformed in the E. coli BL21 (DE3) strain and the expression of SEPT5 protein was induced by IPTG. The SEPT5 protein was shown to be authentic as it was able to be pulled down by a commercial anti-SEPT5 antibody in a co-immunoprecipitation assay. In vivo aggregation of the recombinant protein was limited by cultivation at a reduced temperature of 16 °C. Using co-immunoprecipitation techniques, the purified recombinant SEPT5 protein was used to pull down host's interacting or binding proteins, i.e., proteins of brains of chickens infected with the H5N1 influenza virus. Interacting proteins, such as CRMP2, tubulin proteins, heat-shock proteins and other classes of septins were identified using LCMS/MS. Results from this study suggest that the codon-optimized SEPT5 gene can be efficiently expressed in the E. coli bacterial system producing authentic SEPT5 protein, thus, enabling multiple host's proteins to interact with the SEPT5 protein.