SARS-CoV-2: An Update on Genomics, Risk Assessment, Potential Therapeutics and Vaccine Development.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great threat to public health, being a causative pathogen of a deadly coronavirus disease (COVID-19). It has spread to more than 200 countries and infected millions of individuals globally. Although SARS-CoV-2 has structural/genomic similarities with the previously reported SARS-CoV and MERS-CoV, the specific mutations in its genome make it a novel virus. Available therapeutic strategies failed to control this virus. Despite strict standard operating procedures (SOPs), SARS-CoV-2 has spread globally and it is mutating gradually as well. Diligent efforts, special care, and awareness are needed to reduce transmission among susceptible masses particularly elder people, children, and health care workers. In this review, we highlighted the basic genome organization and structure of SARS-CoV-2. Its transmission dynamics, symptoms, and associated risk factors are discussed. This review also presents the latest mutations identified in its genome, the potential therapeutic options being used, and a brief explanation of vaccine development efforts against COVID-19. The effort will not only help readers to understand the deadly SARS-CoV-2 virus but also provide updated information to researchers for their research work.

Identification and analysis of micro-exons in AP2/ERF and MADS gene families.

Micro-exons are a set of ultrashort exons with lengths ≤ 51 nucleotides. Our previous study revealed that micro-exons were enriched in AP2 domains and K-box domains, which are crucial components of AP2/ERF (APETALA2/ethylene-responsive element-binding protein) and MADS-box (an acronym of MCM1, AGAMOUS, DEFICIENS and SRF) genes, respectively. In this study, we analyzed micro-exons in the AP2/ERF family from 63 species and demonstrated that 76.8% of micro-exons are concentrated in AP2 domains. Most micro-exons appeared in the AP2 subfamily of all the terrestrial plants, but not algae. In addition, micro-exons and AP2 domains are conserved and under negative selection. The MIKC gene is a typical MADS-box gene family in terrestrial plants and includes one MADS-box domain and one K-box domain. A total of 92.3% of micro-exons were observed in K-box domains, and two micro-exons usually encoded a region of K-box domain, which is the key to MADS-box protein polymerization. Furthermore, the micro-exons of the K-box domain had higher ratios of nonsynonymous mutations than those of the AP2 domains. Overall, here we explored the relationships and differences among micro-exons in AP2/ERF and MADS families, and revealed potential functional roles of micro-exons in these domains.

Multiepitope-Based Subunit Vaccine Design and Evaluation against Respiratory Syncytial Virus Using Reverse Vaccinology Approach.

Respiratory syncytial virus (RSV) is primarily associated with respiratory disorders globally. Despite the availability of information, there is still no competitive vaccine available for RSV. Therefore, the present study has been designed to develop a multiepitope-based subunit vaccine (MEV) using a reverse vaccinology approach to curb RSV infections. Briefly, two highly antigenic and conserved proteins of RSV (glycoprotein and fusion protein) were selected and potential epitopes of different categories (B-cell and T-cell) were identified from them. Eminently antigenic and overlapping epitopes, which demonstrated strong associations with their respective human leukocyte antigen (HLA) alleles and depicted collective ~70% coverage of the world's populace, were shortlisted. Finally, 282 amino acids long MEV construct was established by connecting 13 major histocompatibility complex (MHC) class-I with two MHC class-II epitopes with appropriate adjuvant and linkers. Adjuvant and linkers were added to increase the immunogenic stimulation of the MEV. Developed MEV was stable, soluble, non-allergenic, non-toxic, flexible and highly antigenic. Furthermore, molecular docking and molecular dynamics (MD) simulations analyses were carried out. Results have shown a firm and robust binding affinity of MEV with human pathogenic toll-like receptor three (TLR3). The computationally mediated immune response of MEV demonstrated increased interferon-γ production, a significant abundance of immunoglobulin and activation of macrophages which are essential for immune-response against RSV. Moreover, MEV codons were optimized and in silico cloning was performed, to ensure its increased expression. These outcomes proposed that the MEV developed in this study will be a significant candidate against RSV to control and prevent RSV-related disorders if further investigated experimentally.

Epitope-based peptide vaccine design and target site depiction against Middle East Respiratory Syndrome Coronavirus: an immune-informatics study.

BACKGROUND: Middle East Respiratory Syndrome Coronavirus (MERS-COV) is the main cause of lung and kidney infections in developing countries such as Saudi Arabia and South Korea. This infectious single-stranded, positive (+) sense RNA virus enters the host by binding to dipeptidyl-peptide receptors. Since no vaccine is yet available for MERS-COV, rapid case identification, isolation, and infection prevention strategies must be used to combat the spreading of MERS-COV infection. Additionally, there is a desperate need for vaccines and antiviral strategies. METHODS: The present study used immuno-informatics and computational approaches to identify conserved B- and T cell epitopes for the MERS-COV spike (S) protein that may perform a significant role in eliciting the resistance response to MERS-COV infection. RESULTS: Many conserved cytotoxic T-lymphocyte epitopes and discontinuous and linear B-cell epitopes were predicted for the MERS-COV S protein, and their antigenicity and interactions with the human leukocyte antigen (HLA) B7 allele were estimated. Among B-cell epitopes, QLQMGFGITVQYGT displayed the highest antigenicity-score, and was immensely immunogenic. Among T-cell epitopes, MHC class-I peptide YKLQPLTFL and MHC class-II peptide YCILEPRSG were identified as highly antigenic. Furthermore, docking analyses revealed that the predicted peptides engaged in strong bonding with the HLA-B7 allele. CONCLUSION: The present study identified several MERS-COV S protein epitopes that are conserved among various isolates from different countries. The putative antigenic epitopes may prove effective as novel vaccines for eradication and combating of MERS-COV infection.

Peptide vaccine against chikungunya virus: immuno-informatics combined with molecular docking approach.

BACKGROUND: Chikungunya virus (CHIKV), causes massive outbreaks of chikungunya infection in several regions of Asia, Africa and Central/South America. Being positive sense RNA virus, CHIKV replication within the host resulting in its genome mutation and led to difficulties in creation of vaccine, drugs and treatment strategies. Vector control strategy has been a gold standard to combat spreading of CHIKV infection, but to eradicate a species from the face of earth is not an easy task. Therefore, alongside vector control, there is a dire need to prevent the infection through vaccine as well as through antiviral strategies. METHODS: This study was designed to find out conserved B cell and T cell epitopes of CHIKV structural proteins through immuno-informatics and computational approaches, which may play an important role in evoking the immune responses against CHIKV. RESULTS: Several conserved cytotoxic T-lymphocyte epitopes, linear and conformational B cell epitopes were predicted for CHIKV structural polyprotein and their antigenicity was calculated. Among B-cell epitopes "PPFGAGRPGQFGDI" showed a high antigenicity score and it may be highly immunogenic. In case of T cell epitopes, MHC class I peptides 'TAECKDKNL' and MHC class II peptides 'VRYKCNCGG' were found extremely antigenic. CONCLUSION: The study led to the discovery of various epitopes, conserved among various strains belonging to different countries. The potential antigenic epitopes can be successfully utilized in designing novel vaccines for combating and eradication of CHIKV disease.