There is an emergent need to search for possible medications. Method: Utilization of the available sequence information, homology modeling, and in slico docking a number of available medications might prove to be effective in inhibiting the SARS-CoV-2 two main drug targets, the spike glycoprotein, and the 3CL protease. Results: Several compounds were determined from the in silico docking models that might prove to be effective inhibitors for SARS-CoV-2. Several antiviral medications: Zanamivir, Indinavir, Saquinavir, and Remdesivir show potential as and 3CL PRO main proteinase inhibitors and as a treatment for COVID-19. Conclusion: Zanamivir, Indinavir, Saquinavir, and Remdesivir are among the exciting hits on the 3CL PRO main proteinase. It is also exciting to uncover that Flavin Adenine Dinucleotide (FAD) Adeflavin, B2 deficiency medicine, and Coenzyme A, a coenzyme, may also be potentially used for the treatment of SARS-CoV-2 infections. The use of these off-label medications may be beneficial in the treatment of the COVID-19.

Recent advances in 3D printing have led to a rise in the use of 3D printed materials in prosthetics and external medical devices. These devices, while inexpensive, have not been adequately studied for their ability to resist biofouling and biofilm buildup. Bacterial biofilms are a major cause of biofouling in the medical field and, therefore, hospital-acquired, and medical device infections. These surface-attached bacteria are highly recalcitrant to conventional antimicrobial agents and result in chronic infections. During the COVID-19 pandemic, the U.S. Food and Drug Administration and medical officials have considered 3D printed medical devices as alternatives to conventional devices, due to manufacturing shortages. This abundant use of 3D printed devices in the medical fields warrants studies to assess the ability of different microorganisms to attach and colonize to such surfaces. In this study, we describe methods to determine bacterial biofouling and biofilm formation on 3D printed materials. We explored the biofilm-forming ability of multiple opportunistic pathogens commonly found on the human body including Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus to colonize eight commonly used polylactic acid (PLA) polymers. Biofilm quantification, surface topography, digital optical microscopy, and 3D projections were employed to better understand the bacterial attachment to 3D printed surfaces. We found that biofilm formation depends on surface structure, hydrophobicity, and that there was a wide range of antimicrobial properties among the tested polymers. We compared our tested materials with commercially available antimicrobial PLA polymers.

BackgroundEscherichia coli C forms more robust biofilms than other laboratory strains. Biofilm formation and cell aggregation under a high shear force depend on temperature and salt concentrations. It is the last of five E. coli strains (C, K12, B, W, Crooks) designated as safe for laboratory purposes whose genome has not been sequenced.ResultsHere we present the complete genomic sequence of this strain in which we utilized both long-read PacBio-based sequencing and high resolution optical mapping to confirm a large inversion in comparison to the other laboratory strains. Notably, DNA sequence comparison revealed the absence of several genes thought to be involved in biofilm formation, including antigen 43, waaSBOJYZUL for lipopolysaccharide (LPS) synthesis, and cpsB for curli synthesis. The first main difference we identified that likely affects biofilm formation is the presence of an IS3-like insertion sequence in front of the carbon storage regulator csrA gene. This insertion is located 86 bp upstream of the csrA start codon inside the − 35 region of P4 promoter and blocks the transcription from the sigma32 and sigma70 promoters P1-P3 located further upstream. The second is the presence of an IS5/IS1182 in front of the csgD gene. And finally, E. coli C encodes an additional sigma70 subunit driven by the same IS3-like insertion sequence. Promoter analyses using GFP gene fusions provided insights into understanding this regulatory pathway in E. coli.ConclusionsBiofilms are crucial for bacterial survival, adaptation, and dissemination in natural, industrial, and medical environments. Most laboratory strains of E. coli grown for decades in vitro have evolved and lost their ability to form biofilm, while environmental isolates that can cause infections and diseases are not safe to work with. Here, we show that the historic laboratory strain of E. coli C produces a robust biofilm and can be used as a model organism for multicellular bacterial research. Furthermore, we ascertained the full genomic sequence of this classic strain, which provides for a base level of characterization and makes it useful for many biofilm-based applications.

Fibrous phosphorus is a crystalline structure belonging to the extensive family of phosphorus allotropes. The material’s structure consists of 1D tubular layers held together by van der Waals forces and is a semiconductor with an optical band gap of 2.1 eV in its bulk form. With these properties in mind, we developed a facile solution-based method for the fabrication of fibrous phosphorus quantum dots (FPQDs). The FPQDs were prepared by sonicating the material in N-methylpyrrolidone and centrifuging to separate by size. The average size of the quantum dots is 3.8 ± 0.9 nm with a height profile of 2.7 ± 1.3 nm. The as-prepared FPQDs show fluorescence properties with emission in the indigo-blue region and a band gap of 3.3 eV and show remarkable stability when exposed to air and light. As a proof-of-concept of its properties, we used FPQDs as a fluorescent label in the bioimaging of human adenocarcinoma cells.

Biofilm infections have no approved effective medical treatments and can only be disrupted via physical means. This means that any biofilm infection that is not addressable surgically can never be eliminated and can only be managed as a chronic disease. Therefore, there is an urgent need for the development of new classes of drugs that can target the metabolic mechanisms within biofilms which render them recalcitrant to traditional antibiotics. Persister cells within the biofilm structure may play a large role in the enhanced antibiotic recalcitrance of bacteria biofilms. Biofilm persister cells can be resistant to up to 1000 times the minimal inhibitory concentrations of many antibiotics, as compared to their planktonic envirovars; they are thought to be the prokaryotic equivalent of metazoan stem cells. Their metabolic resistance has been demonstrated to be an active process induced by the stringent response that is triggered by the ribosomally-associated enzyme RelA in response to amino acid starvation. This 84-kD pyrophosphokinase produces the “magic spot” alarmones, collectively called (p)ppGpp. These alarmones act by directly regulating transcription by binding to RNA polymerase. These transcriptional changes lead to a major shift in cellular function to both upregulate oxidative stress-combating enzymes and down regulate major cellular functions associated with growth and replication. These changes in gene expression produce the quiescent persister cells. In this work, we describe a hybrid in silico laboratory pipeline for identifying and validating small-molecule inhibitors of RelA for use in the combinatorial treatment of bacterial biofilms as re-potentiators of classical antibiotics.

19Escherichia coli C forms more robust biofilms than the other laboratory strains. Biofilm formation 20 and cell aggregation under a high shear force depends on temperature and salt concentrations. It is 21 the last of five E. coli strains (C, K12, B, W, Crooks) designated as safe for laboratory purposes 22 whose genome has not been sequenced. Here we present the complete genomic sequence of this 23 strain in which we utilized both long-read PacBio-based sequencing and high resolution optical 24 mapping to confirm a large inversion in comparison to the other laboratory strains. Notably, DNA 25 sequence comparison revealed the absence of several genes thought to be involved in biofilm 26 formation, including antigen 43, waaSBOJYZUL for LPS synthesis, and cpsB for curli synthesis. 27 The first main difference we identified that likely affects biofilm formation is the presence of an 28 IS3-like insertion sequence in front of the carbon storage regulator csrA gene. This insertion is 29 located 86 bp upstream of the csrA start codon inside the -35 region of P4 promoter and blocks the 30 transcription from the sigma 32 and sigma 70 promoters P1-P3 located further upstream. The second 31 is the presence of an IS5/IS1182 in front of the csgD gene, which may drive its overexpression in 32 biofilm. And finally, E. coli C encodes an additional sigma 70 subunit overexpressed in biofilm and 33 driven by the same IS3-like insertion sequence. Promoter analyses using GFP gene fusions and 34 total expression profiles using RNA-seq analyses comparing planktonic and biofilm envirovars 35 provided insights into understanding this regulatory pathway in E. coli. 36 IMPORTANCE Biofilms are crucial for bacterial survival, adaptation, and dissemination in 37 natural, industrial, and medical environments. Most laboratory strains of E. coli grown for decades 38 in vitro have evolved and lost their ability to form biofilm, while environmental isolates that can 39 cause infections and diseases are not safe to work with. Here, we show that the historic laboratory 40 3 strain of E. coli C produces a robust biofilm and can be used as a model organism for multicellular 41 bacterial research. Furthermore, we ascertained the full genomic sequence as well as gene 42 expression profiles of both the biofilm and planktonic envirovars of this classic strain, which 43 provide for a base level of characterization and make it useful for many biofilm-based applications. 44 Introduction 45Escherichia coli is a model prokaryote and a key organism for laboratory and industrial 46 applications. E. coli strain C was isolated at the Lister Institute and deposited into the National 47Collection of Type Cultures, London, in 1920 (Strain No. 122). It was characterized as more 48 spherical than other E. coli strains and its nuclear matter was shown to be peripherally distributed 49 in the cell (1). E. coli C, called a restrictionless strain, is permissive for most coliphages and has 50 been used for such studies since the early 1950's (2). Genetic tests ...

Biofilm infections have no effective medical treatments and can only be disrupted via physical means. This means that any biofilm infection that is not addressable surgically can never be eliminated and can only be managed as a chronic disease. Therefore, there is an urgent need for the development of new classes of drugs that can target the metabolic mechanisms within biofilms which render them recalcitrant to traditional antibiotics. This antibiotic recalcitrance of bacterial biofilms can be attributed largely to the formation of persister cells within the biofilm structure. These biofilm persister cells can be resistant to up to 1000 times the minimal inhibitory concentrations of many antibiotics as compared to their planktonic envirovars; they are thought to be the prokaryotic equivalent of metazoan stem cells. Their metabolic resistance has been demonstrated to be an active process induced by the stringent response that is triggered by the ribosomally-associated enzyme RelA in response to amino acid starvation. This 84-kD pyrophosphokinase produces the “magic spot” alarmones, collectively called (p)ppGpp. These alarmones act by directly regulating transcription by binding to RNA polymerase. These transcriptional changes lead to a major shift in cellular function to both upregulate oxidative stress-combating enzymes and down regulate major cellular functions associated with growth and replication. These changes in gene expression produce the quiescent persister cells. In this work, we describe a hybrid in silico-laboratory pipeline for identifying and validating small-molecule inhibitors of RelA for use in the combinatorial treatment of bacterial biofilms as re-potentiators of classical antibiotics.

Since the onset of the SARS-CoV-2 pandemic, the world has witnessed over 617 million confirmed cases and more than 6.54 million confirmed deaths, but the actual totals are likely much higher. The virus has mutated at a significantly faster rate than initially projected, and positive cases continue to surge with the emergence of ever more transmissible variants. According to the CDC, and at the time of this manuscript submission, more than 77% of all current US cases are a result of the B.5 (omicron). The continued emergence of highly transmissible variants makes clear the need for more effective methods of mitigating disease spread. Herein, we have developed an antimicrobial fabric capable of destroying a myriad of microbes including betacoronaviruses. We have demonstrated the capability of this highly porous and nontoxic metal organic framework (MOF), γ-CD-MOF-1, to serve as a host for varied-length benzalkonium chlorides (BACs; active ingredient in Lysol). Molecular docking simulations predicted a binding affinity of up to −4.12 kcal·mol–1, which is comparable to that of other reported guest molecules for this MOF. Similar Raman spectra and powder X-ray diffraction patterns between the unloaded and loaded MOFs, accompanied by a decrease in the Brunauer–Emmett–Teller surface area from 616.20 and 155.55 m2 g–1 respectively, corroborate the suggested potential for pore occupation with BAC. The MOF was grown on polypropylene fabric, exposed to a BAC-loading bath, washed to remove excess BAC from the external surface, and evaluated for its microbicidal activity against various bacterial and viral classes. Significant antimicrobial character was observed against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, bacteriophage, and betacoronavirus. This study shows that a common mask material (polypropylene) can be coated with BAC-loaded γ-CD-MOF-1 while maintaining the guest molecule’s antimicrobial effects.