Demystifying Bacteriocins of Human Microbiota by Genome Guided Prospects: An Impetus to Rekindle the Antimicrobial Research.

The human microbiome is a reservoir of potential bacteriocins that can counteract multidrug resistant bacterial pathogens. Unlike antibiotics, bacteriocins selectively inhibit a spectrum of competent bacteria and are said to safeguard gut commensals, reducing the chance of dysbiosis. Bacteriocinogenic probiotics or bacteriocins of human origin will be more pertinent in human physiological conditions for therapeutic applications to act against invading pathogens. Recent advancement in the omics approach enables the mining of diverse and novel bacteriocins by identifying biosynthetic gene clusters from the human microbial genome, pangenome or shotgun metagenome, which is a breakthrough in the discovery line of novel bacteriocins. This review summarizes the most recent trends and therapeutic potential of bacteriocins of human microbial origin, the advancement in the in silico algorithms and databases in the discovery of novel bacteriocin, and how to bridge the gap between the discovery of bacteriocin genes from big datasets and their in vitro production. Besides, the later part of the review discussed the various impediments in their clinical applications and possible solution to bring them into the frontline therapeutics to control infections, thereby meeting the challenges of global antimicrobial resistance.

Computationally validated SARS-CoV-2 CTL and HTL Multi-Patch vaccines, designed by reverse epitomics approach, show potential to cover large ethnically distributed human population worldwide.

The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is responsible for the COVID-19 outbreak. The highly contagious COVID-19 disease has spread to 216 countries in less than six months. Though several vaccine candidates are being claimed, an effective vaccine is yet to come. A novel reverse epitomics approach, 'overlapping-epitope-clusters-to-patches' method is utilized to identify the antigenic regions from the SARS-CoV-2 proteome. These antigenic regions are named as 'Ag-Patch or Ag-Patches', for Antigenic Patch or Patches. The identification of Ag-Patches is based on the clusters of overlapping epitopes rising from SARS-CoV-2 proteins. Further, we have utilized the identified Ag-Patches to design Multi-Patch Vaccines (MPVs), proposing a novel method for the vaccine design. The designed MPVs were analyzed for immunologically crucial parameters, physiochemical properties and cDNA constructs. We identified 73 CTL (Cytotoxic T-Lymphocyte) and 49 HTL (Helper T-Lymphocyte) novel Ag-Patches from the proteome of SARS-CoV-2. The identified Ag-Patches utilized to design MPVs cover 768 overlapping epitopes targeting 55 different HLA alleles leading to 99.98% of world human population coverage. The MPVs and Toll-Like Receptor ectodomain complex shows stable complex formation tendency. Further, the cDNA analysis favors high expression of the MPVs constructs in a human cell line. We identified highly immunogenic novel Ag-Patches from the entire proteome of SARS CoV-2 by a novel reverse epitomics approach and utilized them to design MPVs. We conclude that the novel MPVs could be a highly potential novel approach to combat SARS-CoV-2, with greater effectiveness, high specificity and large human population coverage worldwide. Communicated by Ramaswamy H. Sarma.

In silico identification and validation of triarylchromones as potential inhibitor against main protease of severe acute respiratory syndrome coronavirus 2.

The ongoing pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 has emerged as a severe threat to the life of human kind. The identification and designing of appropriate and reliable drug molecule for the treatment of COVID-19 patients is the pressing need of the present time. Among different drug targets, the main protease of SARS-CoV-2 is being considered as most effective target. In addition to the drug repurposing, different compounds of natural as well as synthetic origins are being investigated for their efficacy against different drug targets of SARS-CoV-2 virus. In that context, the chromone based natural flavonols have also exhibited significant antiviral properties against different targets of SARS-CoV-2. The in silico studies presented here discloses the efficacy of triarylchromones (TAC) as potential inhibitor against main protease of SARS-CoV-2. The molecular docking and ADMET study performed using 14 arylchromones which could easily be accessed through simple synthetic protocols, revealed best binding affinities in case of TAC-3 (-11.2 kcal/mol), TAC-4 (-10.5 kcal/mol), TAC-6 (-11.2 kcal/mol), TAC-7 (-10.0 kcal/mol). Additional validation studies including molecular dynamics simulation and binding energy calculation using MMGBSA for protein ligand complex for 100 ns revealed the best binding interaction of TAC-3, TAC-4, TAC-6, TAC-7 against main protease of SARS-CoV-2. Moreover, the in vitro and preclinical validation of identified compounds will help us to understand the molecular mechanisms of regulation of TACs against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Vaccine and vaccination as a part of human life: In view of COVID-19.

BACKGROUND: Vaccination created a great breakthrough toward the improvement to the global health. The development of vaccines and their use made a substantial decrease and control in infectious diseases. The abundance and emergence of new vaccines has facilitated targeting populations to alleviate and eliminate contagious pathogens from their innate reservoir. However, along with the infections like malaria and HIV, effective immunization remains obscure and imparts a great challenge to science. PURPOSE AND SCOPE: The novel Corona virus SARS-CoV-2 is the reason for the 2019 COVID-19 pandemic in the human global population, in the first half of 2019. The need for establishing a protected and compelling COVID-19 immunization is a global prerequisite to end this pandemic. SUMMARY AND CONCLUSION: The different vaccine technologies like inactivation, attenuation, nucleic acid, viral vector, subunit, and viral particle based techniques are employed to develop a safe and highly efficient vaccine. The progress in vaccine development for SARS-CoV2 is much faster in the history of science. Even though there exist of lot of limitations, continuous efforts has put forward so as to develop highly competent and effective vaccine for many human and animal linked diseases due to its unlimited prospective. This review article focuses on the historical outlook and the development of the vaccine as it is a crucial area of research where the life of the human is saved from various potential diseases.

In silico identification of potential inhibitor for TP53-induced glycolysis and apoptosis regulator in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the six most common cancer globally and most common cancer in men in India. The metabolic regulation is highly altered and is considered as a hall mark of HNSCC. TP53-induced glycolysis and apoptosis regulator (TIGAR) plays very important role in the development and progression of HNSCC. The aim of our study is to identify a novel FDA approved anticancer inhibitor against mutated TP53-induced glycolysis and apoptosis regulator (TIGAR) through drug repurposing approach. A library of 105 FDA approved anticancer compounds were screened using molecular docking approach against TIGAR (PDB: 3DCY) both Wild-Type (WT) and mutated (Mut). Specific mutations in TIGAR were identified using cBioPortal, a cancer genomics database and mutated structure was modelled using SWISS-MODEL. Out of 510 sequenced cases/patients samples, 17(3%) patients showed alteration in TIGAR [TIGARWT and TIGARMut (R88W)]. The virtual drug screening showed 45 drugs out of 105 high binding affinity with TIGAR, Trabectedin showed highest binding affinity with both TIGARWT (- 13.3 kcal/mol) as well as TIGARMut (R88W) (- 13.8 kcal/mol). The molecular docking studies were validated using molecular dynamics simulation (MD Simulation) of protein-ligand complex of TIGAR and Trabectedin for 100 ns. The MD Simulation of Trabectedin complex showed more stable with TIGARMut (R88W) compared to TIGARWT. Moreover, the string analysis revealed that metabolic-related genes, HK2, PFKFB1, PFKM, PFKP, PFKL, FBP1 are closely associated with TIGAR in HNSCC. Our findings suggest that Trabectedin can be proposed as an inhibitor for [TIGARMut (R88W)] which can be used to target metabolic signalings in HNSCC. However, further investigation and in vitro and in vivo validation our findings required to understand the molecular mechanisms of regulation of Trabectedin in HNSCC.

Genetic characterization of Chikungunya virus 2009 isolates from South India.

Chikungunya Virus (CHIKV) is a single stranded positive sense enveloped RNA virus. Re-emergence of CHIKV caused a massive outbreak with severe clinical manifestation affecting multiple organs. The genetic diversity of CHIKV, which caused recurring outbreaks in India, was studied. Blood samples were collected from suspected human cases of CHIKV infection in Chennai, Tamil Nadu and three Northern districts of Kerala in Southern India during the CHIKV outbreak in 2009. A partial E2 gene segment was amplified by RT-PCR. Among 119 samples 37 samples were positive for CHIKV by RT-PCR. Phylogenetic analysis revealed that the isolated sequences belonged to Indian Ocean Lineage (IOL) of ECSA genotype. The mutational analysis revealed the presence of substitutions such as S299N, T312M, A344T, S375T, V386G, W339R and S375P in the current study. In addition, a novel mutation V386G was observed in all the sequences. Two isolates found with unique substitutions W339R and S375P are reported. The structural analysis of the wild type and mutant proteins revealed that the structural changes are accompanied by modification in the intraprotein interactions.