Altered gut microbiota patterns in COVID-19:Markers for inflammation and disease severity

The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection leads to a severe respiratory illness and alters the gut microbiota,which dynamically interacts with the human immune system.Microbiota alterations include decreased levels of beneficial bacteria and augmentation of opportunistic pathogens.Here,we describe critical factors affecting the microbiota in coronavirus disease 2019(COVID-19)patients.These include,such as gut microbiota imbalance and gastrointestinal symptoms,the pattern of altered gut microbiota composition in COVID-19 patients,and crosstalk between the microbiome and the gut-lung axis/gut-brain-lung axis.Moreover,we have illustrated the hypoxia state in COVID-19 associated gut microbiota alteration.The role of ACE2 in the digestive system,and control of its expression using the gut microbiota is discussed,highlighting the interactions between the lungs,the gut,and the brain during COVID-19 infection.Similarly,we address the gut microbiota in elderly or co-morbid patients as well as gut microbiota dysbiosis of in severe COVID-19.Several clinical trials to understand the role of probiotics in COVID-19 patients are listed in this review.Augmented inflammation is one of the major driving forces for COVID-19 symptoms and gut microbiome disruption and is associated with disease severity.However,understanding the role of the gut microbiota in immune modulation during SARS-CoV-2 infection may help improve therapeutic strategies for COVID-19 treatment.

The 2019 novel coronavirus disease(COVID-19) pandemic: A zoonotic prospective

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a novel coronavirus(CoV),has recently emerged as a significant pathogen for humans and the cause for the recent outbreak of the 2019 novel coronavirus disease(COVID-19)throughout the globe.For developing any preventive measure,an understanding of the zoonotic pattern for this virus is a necessity.We should have a clear knowledge of its reservoir host,its distribution pattern and spreading routes.Information about zoonotic reservoirs and its transmission among them can help to understand the COVID-19 outbreaks.In this article,we discuss about the bats as the zoonotic reservoir of several CoV strains,co-existence of bats and CoV/viruses,the sequence similarity of SARS-CoV-2 with bat SARS-like CoV,the probable source of the origin of SARS-CoV-2 strain and COVID-19 outbreak,intermediate host of CoVs and SARS-CoV-2,human to human transmission and the possibility to maintain the zoonotic barriers.Our knowledge about the zoonotic reservoir of SARS-CoV-2 and its transmission ability may help develop the preventive measures and control for the future outbreak of CoV.

Ebola virus disease: Recent advances in diagnostics and therapeutics

Ebola virus disease(EVD)is associated with haemorrhagic fever in humans and nonhuman primates,with a high rate of fatality(up to 90%).Some outbreaks in human history have proven the lethality of EVD.The recent epidemic of 2014 and 2015 in West Africa was the deadliest of all time(11 284 deaths).To understand the transmission dynamics,we have reviewed the epidemiology of EVD to date.The absence of any licensed vaccines or approved drugs against Ebola virus(EBOV)further highlights the severity and crisis level of EVD.Some organizations(public and private)are making considerable efforts to develop novel therapeutic approaches or vaccines to contain the outbreak of EBOV shortly.Here,we summarized the various potential drugs and vaccines(undergoing multiple phases of clinical trials)that have arisen as an alternative against EBOV,and we highlighted the numerous issues and limitations hindering this process.Alternatively,an increasing focus on strengthening the medical and civic health structure could provide speedy benefits in containing the spread of EVD,as well as offer a resilient foundation for the deployment of novel drugs and vaccines to the affected countries,once such drugs and vaccines become available.

The bacteriophage mu lysis system–A new mechanism of host lysis?

Bacteriophages are viruses that infect bacteria and can choose any one of the two alternative pathways for infection,i.e.,lysis or lysogeny.Phage lysis is one of the conventional biological processes required to spread infection from one bacterium to another.Our analysis suggests that in the paradigm bacteriophage Mu,six proteins might be involved in host cell lysis.Mu has a broad host range,and Mu-like phages were found in both Gram-negative and Gram-positive bacteria.An analysis of the genomes of Mu and Mu-like phages could be useful in elucidating the lysis mechanism in this group of phages.A detailed review of the various mechanisms of phage lysis and different proteins associated with the process will help researchers understand the phage biology and their life cycle in different bacteria.The recent increase in the number of multidrug-resistant(MDR)strains of bacteria and the usual long-term nature of new drug development has encouraged scientists to look for alternative strategies like phage therapy and the discovery of new lysis mechanisms.Understanding the lysis mechanism in the Mu-like phages could be exploited to develop alternative therapeutics to kill drug-resistant pathogenic bacteria.In this review article,we have analyzed the phage Mu-mediated host lysis system,which is unknown till now,and our analysis indicates a possibility of the existence of a new lysis mechanism operating in Mu.

PPARγLBD and its ligand specificity reveal a selection of potential partial agonist:Molecular dynamics based T2D drug discovery initiative

PPARγis a peroxisome proliferator-activated receptor(PPAR)family protein and is a target for type 2 diabetes(T2D).In this paper,we have performed a molecular docking analysis between ligand molecules(CID9816265,CID11608015,CID20251380,CID20251343,CID20556263,CID624491,CID42609928,and CID86287562)and PPARγto determine the ligand specificity.It also helps to understand the ligand-binding domain(LBD)activity of PPARγduring the binding of the ligand.Further,a molecular dynamics simulation study was performed to determine the ligand biding stability in the PPARγLBD.Its ligand specificity informed us about the potentiality of selecting a partial agonist.The study also shows the binding conformation of Ceramicine B having hydrogen bonding affinity with a tricyclic polar head and stabilized theβ-sheet region.On the other hand,the tricyclic polar head of nimbolide also formed hydrogen bonding(Ser342),but it shows a lesser degree of stabilization in theβ-sheet region.It shows the binding conformation of partial agonist(PPARγ)in the Pocket-II of PPARγLBD,which has a significant role in stabilizing theβ-sheet region.It might help to regulate ERK/Cdk5 mediated phosphorylation of Ser245.The study helps us understand the valid pose of a set of ligands confirmation and target protein conformation using docking and molecular dynamics study.This in silico study will also help to initiate a drug discovery process of T2D.

Anti-inflammatory effects of traditional mixed extract of medicinal herbs(MEMH)on monosodium urate crystal-induced gouty arthritis

Korean oriental medicine prescription is widely used for the treatment of gouty diseases. In the present study, we investigated anti-inflammatory effects of modified Korean herbal formulation, mixed extract of medicinal herbs(MEMH), and its modulatory effects on inflammatory mediators associated with gouty arthritis. Both in vitro and in vivo studies were carried out to assess the anti-inflammatory efficacy of MEMH on monosodium urate(MSU) crystals-induced gouty inflammation. MSU crystals stimulated human chondrosarcoma cell line, SW1353, and human primary chondrocytes were treated with MEMH in vitro. The expression levels of pro-inflammatory mediators and metalloproteases were analyzed. The effect of MEMH on NFκB signaling pathway in SW1353 cells was examined. Effect of MEMH on the mR NA expression level of pro-inflammatory mediators and chemotactic factor from human monocytic cell line, THP-1, was also analyzed. The probable role of MEMH in the differentiation process of osteoblast like cells, SaO S-2, after MSU treatment was also observed. To investigate the effects of MEMH in vivo, MSU crystals-induced ankle arthritic model was established. Histopathological changes in affected joints and plasma levels of pro-inflammatory mediators(IL-1β and TNFα) were recorded. MEMH inhibited NFκB signaling pathway and COX-2 protein expression in chondrocytes. MSU-induced mR NA expressions of pro-inflammatory mediators and chemotactic cytokines were suppressed by MEMH. In MSU crystals-induced ankle arthritic mouse model, administration of MEMH relieved inflammatory symptoms and decreased the plasma levels of IL-1β and TNFα. The results indicated that MEMH can effectively inhibit the expression of inflammatory mediators in gouty arthritis, demonstrating its potential for treating gouty arthritis.