Suvro Biswas

Infectious diseases pose a significant threat to human health worldwide. To address this challenge, we conducted a comprehensive study on the leaf and flower extracts of Clitoria ternatea plants. Our research encompassed in vitro assessments of their antibacterial, antibiofilm, antioxidant, and cytotoxic properties. Additionally, we employed in silico screening to identify promising compounds with potential applications in developing novel anti-Escherichia coli medications. Notably, our investigation revealed a remarkable inhibition zone of 13.00±1mm when applying the leaf extract (200μg/ml) against E. coli, showcasing its potent antibacterial properties. Furthermore, both the leaf and flower extracts exhibited substantial biofilm inhibition efficacy against S. aureus, with inhibition percentages of 54 and 58, respectively. In the realm of antioxidant activity, the leaf and flower extracts of C. ternatea displayed noteworthy DPPH free radical scavenging capabilities. Specifically, the leaf extract exhibited a substantial activity of 62.39 at a concentration of 150μg/ml, while the flower extract achieved 44.08 at the same concentration. Our study also evaluated the impact on brine shrimp, where the floral extract displayed a significantly higher mortality rate of 93.33 at a dosage of 200μg/ml compared to the leaf extract. To elucidate potential therapeutic targets, we utilized molecular docking techniques, focusing on the acbR protein (5ENR) associated with antibiotic resistance in E. coli. In this analysis, compounds isolated from the C. ternatea leaf extract, namely D1 (CID-14478556), D2 (CID-6423376), and D3 (CID-20393), exhibited binding energies of 8.2kcal/mol, 6.5kcal/mol, and 6.3kcal/mol, respectively. Additionally, compounds from the flower extract, E1 (CID-5282761), E2 (CID-538757), and E3 (CID-536762), displayed binding energies of 5.4kcal/mol, 5.3kcal/mol, and 5.1kcal/mol, respectively. In conclusion, the leaf and flower extracts derived from C. ternatea represent a promising natural resource with potential therapeutic applications in combating antibiotic-resistant pathogens.

Despite treatments and vaccinations, it remains difficult to develop naturally occurring COVID-19 inhibitors. Here, our main objective is to find potential lead compounds from the retrieved alkaloids with antiviral and other biological properties that selectively target the main SARS-CoV-2 protease (M^pro), which is required for viral replication. In this work, 252 alkaloids were aligned using Lipinskis rule of five and their antiviral activity was then assessed. The prediction of activity spectrum of substances (PASS) data was used to confirm the antiviral activities of 112 alkaloids. Finally, 50 alkaloids were docked with M^pro. Furthermore, assessments of molecular electrostatic potential surface (MEPS), density functional theory (DFT), and absorption, distribution, metabolism, excretion, and toxicity (ADMET) were performed, and a few of them appeared to have potential as candidates for oral administration. Molecular dynamics simulations (MDS) with a time step of up to 100ns were used to confirm that the three docked complexes were more stable. It was found that the most prevalent and active binding sites that limit M^prosactivity are PHE294, ARG298, and GLN110. All retrieved data were compared to conventional antivirals, fumarostelline, strychnidin-10-one (L-1), 2,3-dimethoxy-brucin (L-7), and alkaloid ND-305B (L-16) and were proposed as enhanced SARS-CoV-2 inhibitors. Finally, with additional clinical or necessary study, it may be able to use these indicated natural alkaloids or their analogs as potential therapeutic candidates.

Male infertility is significantly influenced by the plasma-protein sex hormone-binding globulin (SHBG). Male infertility, erectile dysfunction, prostate cancer, and several other male reproductive system diseases are all caused by reduced testosterone bioavailability due to its binding to SHBG. In this study, we have identified 345 phytochemicals from 200 literature reviews that potentially inhibit severe acute respiratory syndrome coronavirus 2. Only a few studies have been done using the SARS-CoV-2 inhibitors to identify the SHBG inhibitor, which is thought to be the main protein responsible for male infertility. In virtual-screening and molecular-docking experiments, cryptomisrine, dorsilurin E, and isoiguesterin were identified as potential SHBG inhibitors with binding affinities of −9.2, −9.0, and −8.8 kcal/mol, respectively. They were also found to have higher binding affinities than the control drug anastrozole (−7.0 kcal/mol). In addition to favorable pharmacological properties, these top three phytochemicals showed no adverse effects in pharmacokinetic evaluations. Several molecular dynamics simulation profiles’ root-mean-square deviation, radius of gyration, root-mean-square fluctuation, hydrogen bonds, and solvent-accessible surface area supported the top three protein–ligand complexes’ better firmness and stability than the control drug throughout the 100 ns simulation period. These combinatorial drug-design approaches indicate that these three phytochemicals could be developed as potential drugs to treat male infertility.

Antibiotic resistance is an alarming threat all over the world, and the biofilm formation efficacy of bacteria is making the situation worse. The antagonistic efficacy of Klebsiella pneumoniae against one of the known fish pathogens, Aeromonas sp., is examined in this study. Moreover, Aeromonas sp.’s biofilm formation ability and in vivo pathogenicity on Artemia salina are also justified here. Firstly, six selected bacterial strains were used to obtain antimicrobial compounds against this pathogenic strain. Among those, Klebsiella pneumoniae, another pathogenic bacterium, surprisingly demonstrated remarkable antagonistic activity against Aeromonas sp. in both in vitro and in vivo assays. The biofilm distrusting potentiality of Klebsiella pneumoniae’s cell-free supernatants (CFSs) was likewise found to be around 56%. Furthermore, the volatile compounds of Klebsiella pneumoniae were identified by GC-MS in order to explore compounds with antibacterial efficacy against Aeromonas sp. through an in silico study, where 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) (PDB: 5B7P) was chosen as a target protein for its unique characteristics and pathogenicity. Several volatile compounds, such as oxime- methoxy-phenyl-, fluoren-9-ol, 3,6-dimethoxy-9-(2-phenylethynyl)-, and 2H-indol-2-one, 1,3-dihydro- showed a strong binding affinity, with free energy of −6.7, −7.1, and −6.4 Kcal/mol, respectively, in complexes with the protein MTAN. Moreover, the root-mean-square deviation, solvent-accessible surface area, radius of gyration, root-mean-square fluctuations, and hydrogen bonds were used to ensure the binding stability of the docked complexes in the atomistic simulation. Thus, Klebsiella pneumoniae and its potential compounds can be employed as an alternative to antibiotics for aquaculture, demonstrating their effectiveness in suppressing Aeromonas sp.

Biofilm inhibition has been identified as a novel drug target for the development of broad-spectrum antibiotics to combat infections caused by drug-resistant bacteria. Although several plant-based compounds have been reported to have anti-biofilm properties, research on the anti-biofilm properties of bacterial bioactive compounds has been sparse. In this study, the efficacy of compounds from a cell-free supernatant of Bacillus subtilis against a biofilm formation of Pseudomonas sp. was studied through in vitro, in vivo and in silico studies. Here, in well diffusion method, Bacillus subtilis demonstrated antibacterial activity, and more than 50% biofilm inhibition activity against Pseudomonas sp. was exhibited through in vitro studies. Moreover, molecular docking and molecular dynamics (MD) simulation gave insights into the possible mode of action of the bacterial volatile compounds identified through GC-MS to inhibit the biofilm-formation protein (PDB ID: 7M1M) of Pseudomonas sp. The binding energy revealed from docking studies ranged from −2.3 to −7.0 kcal mol⁻¹. Moreover, 1-(9H-Fluoren-2-yl)-2-(1-phenyl-1H-ttetrazole5-ylsulfanyl)-ethanone was found to be the best-docked compound through ADMET and pharmacokinetic properties. Furthermore, MD simulations further supported the in vitro studies and formed a stable complex with the tested protein. Thus, this study gives an insight into the development of new antibiotics to combat multi-drug-resistant bacteria.

Honey inhibits bacterial growth due to the high sugar concentration, hydrogen peroxide generation, and proteinaceous compounds present in it. In this study, the antibacterial activity of stingless and sting honey against foodborne pathogenic bacteria isolated from spoiled milk samples was examined. The isolated bacterial strains were confirmed as Bacillus cereus and Listeriamonocytogenes through morphological, biochemical, and 16 s RNA analysis. Physiochemical characterizations of the honey samples revealed that both of the honey samples had an acidic pH, low water content, moderate reducing sugar content, and higher proline content. Through the disc diffusion method, the antibacterial activities of the samples were assayed and better results were observed for the 50 mg/disc honey. Both stingless and sting honey showed the most positive efficacy against Bacillus cereus. Therefore, an in silico study was conducted against this bacterium with some common compounds of honey. From several retrieved constituents of stingless and sting honey, 2,4-dihydroxy-2,5-dimethyl 3(2H)-furan-3-one (furan) and 4H-pyran-4-one,2,3-dihydro of both samples and beta.-D-glucopyranose from the stingless revealed high ligand-protein binding efficiencies for the target protein (6d5z, hemolysin II). The root-mean-square deviation, solvent-accessible surface area, the radius of gyration, root-mean-square fluctuations, and hydrogen bonds were used to ensure the binding stability of the docked complexes in the atomistic simulation and confirmed their stability. The combined effort of wet and dry lab-based work support, to some extent, that the antimicrobial properties of honey have great potential for application in medicine as well as in the food industries.

The emergence of several novel SARS-CoV-2 variants regarded as variants of concern (VOCs) has exacerbated pathogenic and immunologic prominences, as well as reduced diagnostic sensitivity due to phenotype modification-capable mutations. Furthermore, latent and more virulent strains that have arisen as a result of unique mutations with increased evolutionary potential represent a threat to vaccine effectiveness in terms of incoming and existing variants. As a result, resisting natural immunity, which leads to higher reinfection rates, and avoiding vaccination-induced immunization, which leads to a lack of vaccine effectiveness, has become a crucial problem for public health around the world. This study attempts to review the genomic variation and pandemic impact of emerging variations of concern based on clinical characteristics management and immunization effectiveness. The goal of this study is to gain a better understanding of the link between genome level polymorphism, clinical symptom manifestation, and current vaccination in the instance of VOCs.

Mitochondria are major contributors to ATP synthesis, generating more than 90% of the total cellular energy production through oxidative phosphorylation (OXPHOS): metabolite oxidation, such as the β-oxidation of fatty acids, and the Krebs’s cycle. OXPHOS inadequacy due to large genetic lesions in mitochondrial as well as nuclear genes and homo- or heteroplasmic point mutations in mitochondrially encoded genes is a characteristic of heterogeneous, maternally inherited genetic disorders known as mitochondrial disorders that affect multisystemic tissues and organs with high energy requirements, resulting in various signs and symptoms. Several traditional diagnostic approaches, including magnetic resonance imaging of the brain, cardiac testing, biochemical screening, variable heteroplasmy genetic testing, identifying clinical features, and skeletal muscle biopsies, are associated with increased risks, high costs, a high degree of false-positive or false-negative results, or a lack of precision, which limits their diagnostic abilities for mitochondrial disorders. Variable heteroplasmy levels, mtDNA depletion, and the identification of pathogenic variants can be detected through genetic sequencing, including the gold standard Sanger sequencing. However, sequencing can be time consuming, and Sanger sequencing can result in the missed recognition of larger structural variations such as CNVs or copy-number variations. Although each sequencing method has its own limitations, genetic sequencing can be an alternative to traditional diagnostic methods. The ever-growing roster of possible mutations has led to the development of next-generation sequencing (NGS). The enhancement of NGS methods can offer a precise diagnosis of the mitochondrial disorder within a short period at a reasonable expense for both research and clinical applications.

The recent coronavirus outbreak has changed the world’s economy and health sectors due to the high mortality and transmission rates. Because the development of new effective vaccines or treatments against the virus can take time, an urgent need exists for the rapid development and design of new drug candidates to combat this pathogen. Here, we obtained antiviral peptides obtained from the data repository of antimicrobial peptides (DRAMP) and screened their predicted tertiary structures for the ability to inhibit the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using multiple combinatorial docking programs, including PatchDock, FireDock, and ClusPro. The four best peptides, DRAMP00877, DRAMP02333, DRAMP02669, and DRAMP03804, had binding energies of −1125.3, −1084.5, −1005.2, and −924.2 Kcal/mol, respectively, as determined using ClusPro, and binding energies of −55.37, −50.96, −49.25, −54.81 Kcal/mol, respectively, as determined using FireDock, which were better binding energy values than observed for other peptide molecules. These peptides were found to bind with the active cavity of the SARS-CoV-2 main protease; at Glu166, Cys145, Asn142, Phe140, and Met165, in addition to the substrate-binding sites, Domain 2 and Domain 3, whereas fewer interactions were observed with Domain 1. The docking studies were further confirmed by a molecular dynamics simulation study, in which several descriptors, including the root-mean-square difference (RMSD), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), radius of gyration (Rg), and hydrogen bond formation, confirmed the stable nature of the peptide–main protease complexes. Toxicity and allergenicity studies confirmed the non-allergenic nature of the peptides. This present study suggests that these identified antiviral peptide molecules might inhibit the main protease of SARS-CoV-2, although further wet-lab experiments remain necessary to verify these findings.