The “enhanced intracellular survival” (eis) gene of Mycobacterium tuberculosis (Mtb) is involved in the intracellular survival of M. smegmatis. However, its exact effects on host cell function remain elusive. We herein report that Mtb Eis plays essential roles in modulating macrophage autophagy, inflammatory responses, and cell death via a reactive oxygen species (ROS)-dependent pathway. Macrophages infected with an Mtb eis-deletion mutant H37Rv (Mtb-Δeis) displayed markedly increased accumulation of massive autophagic vacuoles and formation of autophagosomes in vitro and in vivo. Infection of macrophages with Mtb-Δeis increased the production of tumor necrosis factor-α and interleukin-6 over the levels produced by infection with wild-type or complemented strains. Elevated ROS generation in macrophages infected with Mtb-Δeis (for which NADPH oxidase and mitochondria were largely responsible) rendered the cells highly sensitive to autophagy activation and cytokine production. Despite considerable activation of autophagy and proinflammatory responses, macrophages infected with Mtb-Δeis underwent caspase-independent cell death. This cell death was significantly inhibited by blockade of autophagy and c-Jun N-terminal kinase-ROS signaling, suggesting that excessive autophagy and oxidative stress are detrimental to cell survival. Finally, artificial over-expression of Eis or pretreatment with recombinant Eis abrogated production of both ROS and proinflammatory cytokines, which depends on the N-acetyltransferase domain of the Eis protein. Collectively, these data indicate that Mtb Eis suppresses host innate immune defenses by modulating autophagy, inflammation, and cell death in a redox-dependent manner.

https://ir.ymlib.yonsei.ac.kr/bitstream/22282913/103277/1/T201006016.pdf

Mycobacterium tuberculosis eis regulates autophagy, inflammation, and cell death through redox-dependent signaling

Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis, with development of DM pandemic in countries where tuberculosis (TB) is also endemic. Understanding the impact of DM on TB and the determinants of co-morbidity is essential in responding to this growing public health problem with improved therapeutic approaches. Despite the clinical and public health significance posed by the dual burden of TB and DM, little is known about the immunological and biochemical mechanisms of susceptibility. One possible mechanism is that an impaired immune response in diabetic patients facilitates either primary infection with Mycobacterium tuberculosis or reactivation of latent TB. DM is associated with immune dysfunction and alterations in the components of the immune system, including altered levels of specific cytokines and chemokines. Some effects of diabetes on adaptive immunity that are potentially relevant to TB defence have been identified in humans. In this review, we summarize current findings regarding the alterations in the innate and adaptive immune responses and immunological mechanisms of susceptibility of DM patients to M. tuberculosis infection and disease. This article is protected by copyright. All rights reserved.

Influence of diabetes mellitus on the immunity to human tuberculosis.

https://www.mdpi.com/2079-6374/9/1/38/pdf

Electrochemical Biosensors as Potential Diagnostic Devices for Autoimmune Diseases.

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic instigated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which changed the daily train of the world's population and cause several dead. Despite the significant efforts made in developing vaccines and therapeutic drugs, there is currently no available effective treatment against this new coronavirus infection, hence the need to continue research which is aimed at limiting the progression of this virus. The present study which has as objective to carry out in silico studies on the metabolites of some Cameroonian medicinal plants of the Asteraceae family with a view to propose potential molecules to fight against COVID-19. The selected plants are commonly used to treat respiratory infectious diseases, and for this reason they may contain some constituents which could exhibit an antiviral activity against SARS-CoV-2. In this work, a set of 74 naturally occurring compounds are computed with SARS-CoV-2 main protease protein (PDB ID: 6lu7) and spike protein (PDB ID: 6m0j) for their affinity and stability using binding energy analysis and molecular docking. Chrysoeriol-7-O-β-D-glucuronopyranoside (compound 16) has showed promising results including excellent Absorption, Distribution, Metabolism and Excretion (ADME) parameters as well as insignificant toxicity. Finally, the stability of this compound is complex with the two proteins validated through molecular dynamics (MD) simulation, they displayed stable trajectory and molecular properties with consistent interaction profile in molecular dynamics simulations. These findings call for further in vitro and in vivo challenges of phytoconstituents against the COVID-19 as a potential agent to fight the spread of this dramatic pandemic.Communicated by Ramaswamy H. Sarma.

Cameroonian medicinal plants as potential candidates of SARS-CoV-2 inhibitors.

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - coronavirus disease 2019 (COVID-19) has raised a severe global public health issue and creates a pandemic situation. The present work aims to study the molecular -docking and dynamic of three pertinent medicinal plants i.e. Eurycoma harmandiana, Sophora flavescens and Andrographis paniculata phyto-compounds against SARS-COV-2 papain-like protease (PLpro) and main protease (Mpro)/3-chymotrypsin-like protease (3CLpro). The interaction of protein targets and ligands was performed through AutoDock-Vina visualized using PyMOL and BIOVIA-Discovery Studio 2020. Molecular docking with canthin-6-one 9-O-beta-glucopyranoside showed highest binding affinity and less binding energy with both PLpro and Mpro/3CLpro proteases and was subjected to molecular dynamic (MD) simulations for a period of 100ns. Stability of the protein-ligand complexes was evaluated by different analyses. The binding free energy calculated using MM-PBSA and the results showed that the molecule must have stable interactions with the protein binding site. ADMET analysis of the compounds suggested that it is having drug-like properties like high gastrointestinal (GI) absorption, no blood-brain barrier permeability and high lipophilicity. The outcome revealed that canthin-6-one 9-O-beta-glucopyranoside can be used as a potential natural drug against COVID-19 protease.

Potential inhibitors of SARS-CoV-2 (COVID 19) proteases PLpro and Mpro/ 3CLpro: molecular docking and simulation studies of three pertinent medicinal plant natural components

A novel coronavirus (SARS-CoV2) has caused a major outbreak in humans around the globe, and it became a severe threat to human healthcare than all other infectious diseases. Researchers were urged to discover and test various approaches to control and prevent such a deadly disease. Considering the emergency and necessity, we screened reported antiviral compounds present in the traditional Indian medicinal plants for the inhibition of SARS-CoV2 main protease. In this study, we used molecular docking to screen 41 reported antiviral compounds that exist in Indian medicinal plants and shown amentoflavone from the plant Torreyanucifera with a higher docking score. Furthermore, we performed a 40 ns atomic molecular dynamics simulation and free binding energy calculations to explore the stability of the top five protein-ligand complexes. Through the article, we insist that the amentoflavone, hypericin and Torvoside H from the traditional Indian medicinal plants may be used as a potential inhibitor of SARS-CoV2 main protease and further biochemical experiments could shed light on understanding the mechanism of inhibition by these plant-derived antiviral compounds. Communicated by Ramaswamy H. Sarma.

Structural basis for the inhibition of SARS-CoV2 main protease by Indian medicinal plant-derived antiviral compounds.

Electrochemical Immunosensors: Working Principle, Types, Scope, Applications, and Future Prospects

Tuberculosis is an airborne, bacterial infectious disease that typically affects the lungs (pulmonary TB) and can also affect other organs and tissues (extrapulmonary TB). TB infection spreads from person to person through the air. TB incidences are typically high in countries with low incomes, low standards of living, high HIV infection rates, malnutrition, and insufficient TB infection control programs. Diagnosing TB infection is critical for effective treatment and in controlling the disease. Treatment for TB is done by following DOTS (Directly Observed Treatment, Short-Course), as was developed by the World Health Organization. DOTS involves an antiregimen with four drugs: isoniazid (H), rifampin (R), pyrazinamide (Z), and either ethambutol (E) or streptomycin (S) for 2 months. After 2 months, the treatment continues with only H and R for a further 4 months. Understanding the host immune mechanisms is very important for treating TB patients.

Kevin Kumar Vijayakumar

Papers

Structural basis for the inhibition of SARS-CoV2 main protease by Indian medicinal plant-derived antiviral compounds.

Electrochemical Immunosensors: Working Principle, Types, Scope, Applications, and Future Prospects

Basics of tuberculosis disease and principles of treatment and their effects

Emerging role of exosomes in hematological malignancies

Liposomes: An emerging carrier for targeting Alzheimer's and Parkinson's diseases