Antiviral activity of Thiosemicarbazones derived from α-amino acids against Dengue virus.

The endemicity and seasonal outbreaks of Dengue disease in most tropical and subtropical countries underscores an urgent need to develop effective prevention and control measures. Development of a Dengue vaccine, which is complicated by the Antibody Dependent Enhancement effect (ADE), a viral inhibitor, seems prudent as it would inhibit the spread of the virus. In vitro methods such as MTT assay and plaque formation unit reduction assays were employed for screening the viral inhibitory property of α-amino acid based Thiosemicarbazides. The results elicits that at concentrations not exceeding the maximum non cytotoxic concentration (MNCC), these compounds completely prevented Dengue virus infection in vero cells as indicated by the absence of cytopathic effects in a dose-dependent manner. The high potency of Bz-Trp-TSC against all four types of Dengue virus infection elevates Thiosemicarbazide as a lead antiviral agent for Dengue disease. Screening small molecules for antiviral activity against the most rapidly spreading mosquito-borne viral disease is being explored by several research groups. Our findings would help to augment the efforts to identify the lead compounds for antiviral therapy to combat the Dengue disease. J. Med. Virol. 89:546-552, 2017. © 2016 Wiley Periodicals, Inc.

Etiological Profile and Clinico Epidemiological Patterns of Acute Encephalitis Syndrome in Tamil Nadu, India.

Introduction: Establishing the etiological cause of acute encephalitis syndrome (AES) is challenging due to the distinct distribution of various etiological agents. This study aims to determine the etiological profiles of both viruses and bacteria and their associated clinico-epidemiological features among the AES suspected cases in Tamil Nadu, India. Methods: Samples of 5136 suspected AES cases from January 2016 to December 2020 (5 years) were subjected to the detection of etiological agents for AES through serological and molecular diagnosis methods. Further, the clinical profile, age- and gender-wise susceptibility of cases, co-infection with other AES etiological agents, and seasonality pattern with respect to various etiological agents were examined. Results: AES positivity was established in 1480 cases (28.82%) among the 5136 suspected cases and the positivity for male and female groups were 57.77% and 42.23%, respectively. The pediatric group was found to be more susceptible than others. Among the etiological agents tested, the Japanese encephalitis virus (JEV) was the predominant followed by Cytomegalovirus, Herpes Simplex virus, Epstein-Barr virus, Varicella Zoster virus, and others. Co-infection with other AES etiological agents was observed in 3.5% of AES-positive cases. Seasonality was observed only for vector-borne diseases such as JEV, dengue virus, and West Nile virus infections in this study. Conclusion: AES was found to be a significant burden for Tamil Nadu with a diverse etiological spectrum including both sporadic and outbreak forms. Overlapping clinical manifestations of AES agents necessitate the development of region-specific diagnostic algorithm with distinct etiological profiles for early detection and effective case management.

Epitope Identification and Designing a Potent Multi-epitope Vaccine Construct against SARS-CoV-2 Including the Emerging Variants.

Introduction: The emergence of a novel coronavirus in China has turned into a SARS-CoV-2 pandemic with high fatality. As vaccines are developed through various strategies, their immunogenic potential may drastically vary and thus pose several challenges in offering immune responses against the virus. Methods: In this study, we adopted an immunoinformatics-aided approach for developing a new multi-epitope vaccine construct (MEVC). In silico approach was taken for the identification of B-cell and T-cell epitopes in the Spike protein, for MEVC various cytotoxic T-lymphocyte, helper T-lymphocyte, and B-cell epitopes with the highest affinity for the respective HLA alleles were assembled and joined by linkers. Results: The computational data suggest that the MEVC is nontoxic, nonallergenic and thermostable and elicit both humoral and cell-mediated immune responses. Subsequently, the biological activity of MEVC was assessed by bioinformatic tools using the interaction between the vaccine candidate and the innate immune system receptors TLR3 and TLR4. The epitopes of the construct were analyzed with that of the strains belonging to various clades including the emerging variants having multiple unique mutations in S protein. Conclusions: Due to the advantageous features, the MEVC can be tested in vitro for more practical validation and the study offers immense scope for developing a potential vaccine candidate against SARS-CoV-2 in view of the public health emergency associated with COVID-19 disease caused by SARS-CoV-2.

Phylodynamic Pattern of Genetic Clusters, Paradigm Shift on Spatio-Temporal Distribution of Clades, and Impact of Spike Glycoprotein Mutations of SARS-CoV-2 Isolates from India.

INTRODUCTION: The COVID-19 pandemic is associated with high morbidity and mortality, with the emergence of numerous variants. The dynamics of SARS-CoV-2 with respect to clade distribution is uneven, unpredictable and fast changing. METHODS: Retrieving the complete genomes of SARS-CoV-2 from India and subjecting them to analysis on phylogenetic clade diversity, Spike (S) protein mutations and their functional consequences such as immune escape features and impact on infectivity. Whole genome of SARS-CoV-2 isolates (n = 4,326) deposited from India during the period from January 2020 to December 2020 is retrieved from Global Initiative on Sharing All Influenza Data (GISAID) and various analyses performed using in silico tools. RESULTS: Notable clade dynamicity is observed indicating the emergence of diverse SARS-CoV-2 variants across the country. GR clade is predominant over the other clades and the distribution pattern of clades is uneven. D614G is the commonest and predominant mutation found among the S-protein followed by L54F. Mutation score prediction analyses reveal that there are several mutations in S-protein including the RBD and NTD regions that can influence the virulence of virus. Besides, mutations having immune escape features as well as impacting the immunogenicity and virulence through changes in the glycosylation patterns are identified. CONCLUSIONS: The study has revealed emergence of variants with shifting of clade dynamics within a year in India. It is shown uneven distribution of clades across the nation requiring timely deposition of SARS-CoV-2 sequences. Functional evaluation of mutations in S-protein reveals their significance in virulence, immune escape features and disease severity besides impacting therapeutics and prophylaxis.