Biology subjects

Singh, O. N.

Publications and source records attributed to Singh, O. N..

4 recordsLinked to original sources

bioRxiv2024

Immunogenicity and protection efficacy of self-amplifying and circular mRNA vaccines for SARS-CoV-2

Recent advances in vaccine technology have positioned messenger RNA (mRNA) vaccines as safe and reliable options for human use. Conventionally, mRNA vaccines were designed using linear or self-amplifying mRNA (SAM), the latter considered to be superior. However, limited success was achieved with SAM vaccines during the COVID-19 pandemic. Further, studies on Circular mRNA (Circ-RNA) vaccines against the SARS-CoV-2, Ebola and monkey pox proved their efficacy. Circ-RNAs are highly stable, neither they induce inflammatory response nor require any extracellular protein for their function. Here, we compared the efficacy of SAM- and Circ-RNA vaccines using the SARS-CoV-2-RBD (receptor binding domain) as the antigen. Both SAM-RBD and Circ-RBD induced a comparable anti-RBD IgG titer and virus-neutralizing antibody titer. However, the latter induced a significantly higher memory T-cell response. Immunization with SAM- and Circ-RBD showed no mortality and improved lung pathophysiology against acute SARS-CoV-2 infection in mice. The Circ-RBD vaccine is stable for 4 weeks at 40C. A bivalent vaccine containing Circ-RBD of both delta and omicron SARS-CoV-2 variants potently neutralized these viruses. These findings demonstrate Circ-RNA-RBD as an excellent vaccine candidate against COVID-19 and also provide a platform for developing bivalent Circ-RNA vaccine candidates against SARS-CoV-2 or other viruses with rapidly emerging variants.

microbiology↗

bioRxiv2022

Human endogenous retrovirus-R envelope is a host restriction factor against severe acute respiratory syndrome-coronavirus-2

Coronavirus induced disease-19 (COVID-19), caused by the SARS-CoV-2 remains a major global health challenge. Human endogenous retroviruses (HERVs) represent retroviral elements that got integrated into the ancestral human genome. HERVs are important in development and diseases, including cancer, inflammation and viral infections. Here, we analyzed the expression of several HERVs in SARS-CoV-2 infected cells and observed increased activity of HERV-E, HERV-V, HERV-FRD, HERV-MER34, HERV-W and HERV-KHML2. In contrast, HERV-R-envelope was downregulated in cell-based models and COVID-19 patient PBMCs. HERV-R overexpression inhibited SARS-CoV-2 replication, suggesting its antiviral action. Further studies demonstrated the role of extracellular signal-regulated kinase (ERK) in regulating HERV-R antiviral activity. Cross-talk between the ERK and p38 MAPK controls HERV-R envelope synthesis, which in turn modulates the replication of SARS-CoV-2. These findings establish the importance of HERV-R envelope as a host restriction factor against SARS-CoV-2 and illustrate the advantage of integration and evolutionary maintenance of retroviral-elements in the human genome.

microbiology↗

bioRxiv2022

Dietary αKG inhibits SARS CoV-2 infection and rescues inflamed lungs to restore normal O2 saturation in animals

Our recent works described the rescue effect of -ketoglutarate (KG, a metabolite of Krebs cycle) on thrombosis and inflammation in animals. KG augments activity of prolyl hydroxylase 2 (PHD2), which in turn degrades proline residues of substrates like phosphorylated Akt (pAkt) and hypoxia inducible factor (HIF). Here we describe the inhibitory effect of octyl KG on pAkt as well as on HIF1/HIF2, and in turn decreasing SARS CoV-2 replication in Vero E6 cells. KG failed to inhibit the viral replication and Akt phosphorylation in PHD2-knockdown U937 cells transiently expressing ACE2. Contrastingly, triciribine (TCN, an Akt-inhibitor) inhibited viral replication alongside a downmodulation of pAkt in PHD2-KD cells. Dietary KG significantly inhibited viral infection and rescued hamsters from thrombus formation and inflammation in lungs, the known causes of acute respiratory distress syndrome (ARDS) in COVID-19. KG supplementation also reduced the apoptotic death of lung tissues in infected animals, alongside a downmodulation of pAkt and HIF2. KG supplementation neither affected IgG levels against SARS CoV-2 RBD protein nor altered the neutralization antibody response against SARS CoV-2. It did not interfere with the percentage of interferon-{gamma} positive (IFN{gamma}+) CD4+ and IFN{gamma}+CD8+ T cells in infected animals. The extended work in balb/c mice transiently expressing ACE2 showed a similar effect of KG in reducing accumulation of inflammatory immune cells and cytokines, including IL6, IL1{beta} and TNF, in lungs as well as in circulation of infected animals. Pro-thrombotic markers like platelet microparticles and platelet-leukocyte aggregates were reduced significantly in infected mice after KG supplementation. Importantly, KG supplementation restored the O2 saturation (SpO2) in circulation of SARS CoV-2 infected hamsters and mice, suggesting a potential therapeutic role of this metabolite in COVID-19 treatment.

pathology↗

bioRxiv2020

Identification of QTLs for high grain yield and component traits in New Plant Types of rice

A panel of 60 genotypes consisting of New Plant Types (NPTs) along with indica, tropical and temperate japonica genotypes were phenotypically evaluated for four seasons in irrigated situation for grain yield per se and component traits. Twenty NPT genotypes were found to be promising with an average grain yield of 5.45 to 8.8 t/ha. A total of 85 SSR markers were used in the study to identify QTLs associated with grain yield per se and related traits. Sixty-six (77.65%) markers were found to be polymorphic. The PIC values varied from 0.516 to 0.92 with an average of 0.704. A moderate level of genetic diversity (0.39) was detected among genotypes. Variation to the tune of 8% within genotypes, 68% among the genotypes within the population and 24% among the populations were observed (AMOVA). The association analysis using GLM and MLM models led to the identification of 30 and 10 SSR markers were associated with 70 and 16 QTLs, respectively. Thirty novel QTLs linked with 16 SSRs were identified to be associated with eleven traits, namely, tiller number (qTL-6.1, qTL-11.1, qTL-4.1), panicle length (qPL-1.1, qPL-5.1, qPL-7.1, qPL-8.1), flag leaf length (qFLL-8.1, qFLL-9.1), flag leaf width (qFLW-6.2, qFLW-5.1, qFLW-8.1, qFLW-7.1), total no. of grains (qTG-2.2, qTG-a7.1), thousand-grain weight (qTGW-a1.1, qTGW-a9.2, qTGW-5.1, qTGW-8.1), fertile grains (qFG-7.1), seed length-breadth ratio (qSlb-3.1), plant height (qPHT-6.1, qPHT-9.1), days to 50% flowering (qFD-1.1) and grain yield per se (qYLD-5.1, qYLD-6.1a, qYLD-11.1). This information could be useful for identification of highly potential parents for development of transgressive segregants. Moreover, super rice genotypes could be developed through pyramiding of these QTLS for important yield traits for prospective increment in yield potentiality and breaking yield ceiling.

plant biology↗