Most accurate mutations in SARS-CoV-2 genomes identified in Uzbek patients show novel amino acid changes.

Purpose: The rapid changes in the coronavirus genomes created new strains after the first variation was found in Wuhan in 2019. SARS-CoV-2 genotypes should periodically undergo whole genome sequencing to control it because it has been extremely helpful in combating the virus. Many diagnoses, treatments, and vaccinations have been developed against it based on genome sequencing. With its practical implications, this study aimed to determine changes in the delta variant of SARS-CoV-2 widespread in Uzbekistan during the pandemic by genome sequencing, thereby providing crucial insights for developing effective control strategies that can be directly applied in the field. Design: We meticulously generated 17 high-quality whole-genome sequence data from 48 SARS-CoV-2 genotypes of COVID-19 patients who tested positive by PCR in Tashkent, Uzbekistan. Our rigorous approach, which includes stringent quality control measures and multiple rounds of verification, ensures the accuracy and reliability of our findings. Methods: Our study employed a unique combination of genome sequencing and bioinformatics web tools to analyze amino acid (AA) changes in the virus genomes. This approach allowed us to understand the genetic changes in the delta variant of SARS-CoV-2 widespread in Uzbekistan during the pandemic. Results: Our study revealed significant nucleotide polymorphisms, including non-synonymous (missense) and synonymous mutations in the coding regions of the sequenced sample genomes. These findings, categorized by phylogenetic analysis into the G clade (or GK sub-clade), contribute to our understanding of the delta variant of SARS-CoV-2 widespread in Uzbekistan during the pandemic. A total of 134 mutations were identified, consisting of 65 shared and 69 unique mutations. These nucleotide changes, including one frameshift mutation, one conservative and disruptive insertion-deletion, four upstream region mutations, four downstream region mutations, 39 synonymous mutations, and 84 missense mutations, are crucial in the ongoing battle against the virus. Conclusion: The comprehensive whole-genome sequencing data presented in this study aids in tracing the origins and sources of circulating SARS-CoV-2 variants and analyzing emerging variations within Uzbekistan and globally. The genome sequencing of SARS-CoV-2 from samples collected in Uzbekistan in late 2021, during the peak of the pandemic's second wave nationwide, is detailed here. Following acquiring these sequences, research efforts have focused on developing DNA and plant-based edible vaccines utilizing prevalent SARS-CoV-2 strains in Uzbekistan, which are currently undergoing clinical trials.

Tomato-made edible COVID-19 vaccine TOMAVAC induces neutralizing IgGs in the blood sera of mice and humans.

Plant-based edible vaccines that provide two-layered protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outweigh the currently used parenteral types of vaccines, which predominantly cause a systemic immune response. Here, we engineered and selected a transgenic tomato genotype (TOMAVAC) that stably synthesized an antigenic S1 protein of SARS-CoV-2. Two-course spaced force-feeding of mice with ≈5.4 µg/ml TOMAVAC increased up to 16-fold the synthesis of RBD-specific NAbs in blood serum and the significant induction of S-IgA in intestinal lavage fluid. In a surrogate virus neutralization test, TOMAVAC-induced NAbs had 15-25% viral neutralizing activity. The results suggested early evidence of the immunogenicity and protectivity of TOMAVAC against the coronavirus disease 2019 (COVID-19) infection. Furthermore, we observed a positive trend of statistically significant 1.2-fold (average of +42.28 BAU/ml) weekly increase in NAbs in the volunteers' serum relative to the initial day. No severe side effects were observed, preliminarily supporting the safety of TOMAVAC. With the completion of future large-scale studies, higher-generation TOMAVAC should be a cost-effective, ecologically friendly, and widely applicable novel-generation COVID-19 vaccine, providing two-layered protection against SARS-CoV-2.

Profiling of the most reliable mutations from sequenced SARS-CoV-2 genomes scattered in Uzbekistan.

Due to rapid mutations in the coronavirus genome over time and re-emergence of multiple novel variants of concerns (VOC), there is a continuous need for a periodic genome sequencing of SARS-CoV-2 genotypes of particular region. This is for on-time development of diagnostics, monitoring and therapeutic tools against virus in the global pandemics condition. Toward this goal, we have generated 18 high-quality whole-genome sequence data from 32 SARS-CoV-2 genotypes of PCR-positive COVID-19 patients, sampled from the Tashkent region of Uzbekistan. The nucleotide polymorphisms in the sequenced sample genomes were determined, including nonsynonymous (missense) and synonymous mutations in coding regions of coronavirus genome. Phylogenetic analysis grouped fourteen whole genome sample sequences (1, 2, 4, 5, 8, 10-15, 17, 32) into the G clade (or GR sub-clade) and four whole genome sample sequences (3, 6, 25, 27) into the S clade. A total of 128 mutations were identified, consisting of 45 shared and 83 unique mutations. Collectively, nucleotide changes represented one unique frameshift mutation, four upstream region mutations, six downstream region mutations, 50 synonymous mutations, and 67 missense mutations. The sequence data, presented herein, is the first coronavirus genomic sequence data from the Republic of Uzbekistan, which should contribute to enrich the global coronavirus sequence database, helping in future comparative studies. More importantly, the sequenced genomic data of coronavirus genotypes of this study should be useful for comparisons, diagnostics, monitoring, and therapeutics of COVID-19 disease in local and regional levels.