The novel coronavirus disease, caused by severe acute respiratory 2 (SARS-CoV-2), rapidly spreading around the world, poses a major threat to global public health. Herein, we demonstrated binding mechanism of PF-07321332, α-ketoamide, lopinavir, and ritonavir 3-chymotrypsin-like-protease (3CLpro) means docking molecular dynamic (MD) simulations. analysis MD trajectories 3CLpro with revealed that 3CLpro–PF-07321332 3CLpro–α-ketoamide complexes remained stable compared 3CLpro–ritonavir...

The rapid spread of the virus, surge in number deaths, and unavailability specific SARS-CoV-2 drugs thus far necessitate identification with anti-COVID-19 activity. enters host cell assembles a multisubunit RNA-dependent RNA polymerase (RdRp) complex viral nonstructural proteins that plays substantial role transcription replication genome. Therefore, RdRp is among most suitable targets viruses. Our aim was to investigate FDA approved antiviral having potential inhibit replication....

Middle East respiratory syndrome coronavirus (MERS-CoV) has evolved to navigate through the sophisticated network of a host's immune system. The evasion mechanism including type 1 interferon and protein kinase R-mediated antiviral stress responses been recently attributed involvement MERS-CoV 4a (p4a) that masks viral dsRNA. However, structural how p4a recognizes establishes contacts with dsRNA is not well explained. In this study, we report dynamic deployed by engage make it unavailable...

Toll-like receptors (TLRs) are a unique category of pattern recognition that recognize distinct pathogenic components, often utilizing the same set downstream adaptors. Specific molecular features extracellular, transmembrane (TM), and cytoplasmic domains TLRs crucial for coordinating complex, innate immune signaling pathway. Here, we constructed full-length structural model TLR4-a widely studied member interleukin-1 receptor/TLR superfamily-using homology modeling, protein-protein docking,...

Antimicrobial resistance (AMR) is a major global public health concern mainly affecting low- and middle-income countries (LMICs) due to lack of awareness, inadequate healthcare sanitation infrastructure, other environmental factors. In this study, we aimed link microbial assembly covariates (body mass index, smoking, use antibiotics) gut microbiome structure correlate the predictive antimicrobial gene prevalence (piARG) using PICRUSt2. We examined gastrointestinal oral profiles healthy...

Excessive signaling by the proinflammatory cytokine TNF is involved in several autoimmune diseases, including rheumatoid arthritis (RA). However, unlike approved biologics currently used to treat this and other conditions, commercially available small-molecule inhibitors of trimerization are cytotoxic or exhibit low potency. Here, we report a TNF-inhibitory molecule (TIM) that reduced vitro was an effective treatment mouse model RA. The initial lead compound, TIM1, attenuated TNF-induced...

Lipopeptides have a widespread role in different pathways of Bacillus subtilis; they can act as antagonists, spreader and immunostimulators.Plipastatin, an antifungal antibiotic, is one the most important lipopeptide nonribosomly produced by subtilis.Plipastatin has strong fungitoxic activity involve inhibition phospholipase A2 biofilm formation.For better understanding molecule pathway which plipastatin synthesized, we present computationally predicted structure using homology...

We report the initial characterization of gastrointestinal tract (gut) and oral microbiota (bacteria) in 32 urban Pakistani adults. Study participants were between ages 18 40, had body mass index 25 Kg/m2, students or early-career professionals. These individuals donated a total 61 samples (32 gut 29 oral) that subjected to 16S ribosomal RNA (rRNA) gene sequencing. Microbiome composition was compared against uBiome database selected who self-reported be excellent health. observed strong...

Toll-like receptor (TLR) signaling plays a critical role in the induction and progression of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, experimental encephalitis, type 1 diabetes mellitus neurodegenerative diseases. Deciphering antigen recognition by antibodies provides insights defines mechanism action into immune responses. Multiple strategies, including phage display hybridoma technologies, have been used to enhance affinity for their respective...

Mycoplasma genitalium is a human pathogen associated with several sexually transmitted diseases.The complete genome of M. G37 has been sequenced and provides an opportunity to understand the pathogenesis identification therapeutic targets.However, understanding bacterial function requires proper annotation its proteins.The consists 475 proteins.Among these, 94 are without any known described as 'hypothetical proteins'.We selected MG_237 for sequence structural analysis using bioinformatics...

Toll-like receptor 3 (TLR3) provides the host with antiviral defense by initiating an immune signaling cascade for production of type I interferons. The X-ray structures isolated TLR3 ectodomain (ECD) and transmembrane (TM) domains have been reported; however, structure a membrane-solvated, full-length remains elusive. We investigated all-residue model embedded inside phospholipid bilayer using molecular dynamics simulations. TLR3-ECD exhibited ~30°–35° tilt on membrane due to electrostatic...

The persistent use of antibiotics for many years has transformed numerous organisms into multiple drug resistant. This made the domain discovery vital to cure several infectious diseases. Staphylococcus aureus is a Gram-positive bacterium that developed resistance drugs. main objective this study identify potential targets. subtractive genomics approach was applied screen out proteins. For identification and characterization non-homologous essential proteins, different bioinformatics tools...

ABSTRACT We describe the characterization of gastrointestinal tract (gut) and oral microbiota (bacteria) in 32 urban Pakistani adults representing seven major geographies six ethnicities country. Study participants were between ages 18 40, had body mass index 25 Kg/m 2 , early-career students or professionals belonging to cities These individuals donated a total 61 samples (32 gut 29 oral) that subjected 16S ribosomal RNA (rRNA) gene sequencing. Microbiome composition was compared against...