Whole proteome screening and identification of potential epitopes of SARS-CoV-2 for vaccine design-an immunoinformatic, molecular docking and molecular dynamics simulation accelerated robust strategy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the most cryptic pandemic outbreak of the 21st century, has gripped more than 1.8 million people to death and infected almost eighty six million. As it is a new variant of SARS, there is no approved drug or vaccine available against this virus. This study aims to predict some promising cytotoxic T lymphocyte epitopes in the SARS-CoV-2 proteome utilizing immunoinformatic approaches. Firstly, we identified 21 epitopes from 7 different proteins of SARS-CoV-2 inducing immune response and checked for allergenicity and conservancy. Based on these factors, we selected the top three epitopes, namely KAYNVTQAF, ATSRTLSYY, and LTALRLCAY showing functional interactions with the maximum number of MHC alleles and no allergenicity. Secondly, the 3D model of selected epitopes and HLA-A*29:02 were built and Molecular Docking simulation was performed. Most interestingly, the best two epitopes predicted by docking are part of two different structural proteins of SARS-CoV-2, namely Membrane Glycoprotein (ATSRTLSYY) and Nucleocapsid Phosphoprotein (KAYNVTQAF), which are generally target of choice for vaccine designing. Upon Molecular Docking, interactions between selected epitopes and HLA-A*29:02 were further validated by 50 ns Molecular Dynamics (MD) simulation. Analysis of RMSD, Rg, SASA, number of hydrogen bonds, RMSF, MM-PBSA, PCA, and DCCM from MD suggested that ATSRTLSYY is the most stable and promising epitope than KAYNVTQAF epitope. Moreover, we also identified B-cell epitopes for each of the antigenic proteins of SARS CoV-2. Findings of our work will be a good resource for wet lab experiments and will lessen the timeline for vaccine construction.Communicated by Ramaswamy H. Sarma.

Nature-Derived Hit, Lead, and Drug-Like Small Molecules: Current Status and Future Aspects Against Key Target Proteins of Coronaviruses.

BACKGROUND: COVID-19 pandemic, the most unprecedented event of the year 2020, has brought millions of scientists worldwide in a single platform to fight against it. Though several drugs are now in the clinical trial, few vaccines are available on the market already, but the lack of an effect of those is making the situation worse. AIM OF THE STUDY: In this review, we demonstrated comprehensive data of natural antiviral products showing activities against different proteins of Human Coronaviruses (HCoV) that are responsible for its pathogenesis. Furthermore, we categorized the compounds into the hit, lead, and drug based on the IC50/EC50 value, drug-likeness, and lead-likeness test to portray their potentiality to be a drug. We also demonstrated the present status of our screened antiviral compounds with respect to clinical trials and reported the lead compounds that can be promoted to clinical trial against COVID-19. METHODS: A systematic search strategy was employed focusing on Natural Products (NPs) with proven activity (in vitro, in vivo, or in silico) against human coronaviruses, in general, and data were gathered from databases like PubMed, Web of Science, Google Scholar, SciVerse, and Scopus. Information regarding clinical trials retrieved from the Clinical Trial Database. RESULTS: Total "245" natural compounds were identified initially from the literature study. Among them, Glycyrrhizin, Caffeic acid, Curcumin is in phase 3, and Tetrandrine, Cyclosporine, Tacrolimus, Everolimus are in phase 4 clinical trial. Except for Glycyrrhizin, all compounds showed activity against COVID-19. CONCLUSION: In summary, our demonstrated specific small molecules with lead and drug-like capabilities clarified their position in the drug discovery pipeline and proposed future research against COVID-19.

Bilingual phonological development across generations: Segmental accuracy and error patterns in second- and third-generation British Bengali children.

INTRODUCTION: While developmental norms for speech sound development have been widely reported for monolingual children, and increasingly for bilingual children, little is known about speech sound development across different generations of children growing up in heritage language settings. The purpose of the present study was to gain a better understanding of inter-generational differences in the phonological development of British Bengali children. METHODS: Typically-developing second-generation and third-generation Bengali heritage children living in Wales (n=19), aged between 4 and 5 years, participated in a picture-naming task in Sylheti and English. The single-word speech samples were transcribed phonetically and analyzed in terms of consonant and vowel accuracy measures, and error patterns. Subsequently, logistic mixed-effects regression models were fitted to identify the factors that predict accurate speech patterns in the children's productions. RESULTS: The results revealed high levels of accuracy in consonant and vowel production by both sets of children, particularly in English. On Sylheti consonants, second-generation children significantly outperformed third-generation children, however only on language-specific sounds. In contrast, generation was not a significant predictor for accuracy on English consonants, but all children performed better on shared sounds than on English-specific categories, and on stops than affricates. The third-generation children exhibited a greater number of error types in Sylheti than the second-generation children, and more common replacement of Sylheti dental stops with alveolars. CONCLUSION: The results suggest that third-generation children have less developed pronunciation patterns in the heritage language, but not the majority language, than their age-matched second-generation peers, however only on language-specific sounds. These findings indicate that differentiating between the phonological norms of monolingual and bilingual children may not be clinically sufficiently sensitive, at least in the minority language, and that more fine-grained language use variables, such as the generation to which a bilingual child belongs, need to be considered.

Identification of salt tolerant rice cultivars via phenotypic and marker-assisted procedures.

Eleven genotypes, including the salt tolerant cultivar Pokkali as check, were used to evaluate salinity tolerance phenotypically and genotypically. Three selected SSR primers viz., RM7075, RM336 and RM253 were used to evaluate rice genotypes for salt tolerance. Two setups were maintained for this study viz., the seedling and reproductive stages. Phenotyping at the seedling stage was done in hydroponic system using salinized (EC 12 dS m(-1)) nutrient solution and at the reproductive stage using salinized tap water (EC 6 dS m(-1)). IRRI standard protocol was followed to evaluate salinity tolerance in rice. The genotypes having similar banding pattern with Pokkali were considered as tolerant. Phenotypically, three genotypes Pokkali, THDB and TNDB-100 and five genotypes RD-2586, TNDB-100, Dhol Kochuri, PNR-519 and Pokkali were identified as salt tolerant at the seedling and reproductive stages, respectively. These genotypes were also identified as salt tolerant genotypically (with markers). Through phenotypic and genotypic study, five genotypes viz., Pokkali, Dhol Kochuri, RD-2586, TNDB-100 and PNR-519 were identified as salt tolerant. Therefore, these microsatellite markers used in this study could be efficiently used for identification of salt tolerant rice varieties in marker-assisted breeding and quantitative trait loci analysis.