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Insights into the evolutionary and prophylactic analysis of SARS-CoV-2: A review.

ABSTRACT: In late 2019, following the emergence of a β-originated SARS-CoV-2, phylogenetic and evolutionary approaches have been demonstrated to strengthen the diagnostic and prophylactic stratagem of COVID-19 at an unprecedented level. Despite its clinical prominence, the SARS-CoV-2 gene set remains largely irrefutable by impeding the dissection of COVID-19 biology. However, many pieces of molecular and serological evidence have predicted that SARS-CoV-2 related viruses carry their roots from bats and pangolins of South East Asia. Analysis of viral genome predicts that point mutations at a rate of 10^-4 nucleotides per base in the receptor-binding domain allow the emergence of new SARS-CoV-2 genomic variants at regular intervals. Research in the evolution of molecular pathways involved in emergence of pandemic is critical for the development of therapeutics and vaccines as well as the prevention of future zoonosis. By determining the phyletic lineages of the SARS-CoV-2 genomic variants and those of the conserved regions in the accessory and spike proteins of all the SARS-related coronaviruses, a universal vaccine against all human coronaviruses could be formulated which would revolutionize the field of medicine. This review highlighted the current development and future prospects of antiviral drugs, inhibitors, mesenchymal stem cells, passive immunization, targeted immune therapy and CRISPR-Cas-based prophylactic and therapeutic strategies against SARS-CoV-2. However, further investigations on Covid-19 pathogenesis is required for the successful fabrication of successful antivirals.

SUBMITTER: Akram F

PROVIDER: S-EPMC8610842 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The author apply concepts and tools from evolutionary medicine to understanding the SARS-CoV-2 pandemic. The pandemic represents a mismatched conflict, with dynamics and pathology apparently driven by three main factors: (i) bat immune systems that rely on low inflammation but high efficacy of interferon-based defenses; (ii) viral tactics that differentially target the human interferon system, leading to substantial asymptomatic and pre-symptomatic transmission; and (ii) high mortality caused by hyper-inflammatory and hyper-coagulatory phenotypes, that represent dysregulated tradeoffs whereby collateral immune-induced damage becomes systemic and severe. This framework can explain the association of mortality with age (which involves immune life-history shifts towards higher inflammation and coagulation and reduced adaptive immunity), and sex (since males senesce faster than females). Genetic-risk factors for COVID-19 mortality can be shown, from a phenome-wide association analysis of the relevant SNPs, to be associated with inflammation and coagulation; the phenome-wide association study also provides evidence, consistent with several previous studies, that the calcium channel blocking drug amlodipine mediates risk of mortality. Lay Summary: SARS-CoV-2 is a bat virus that jumped into humans. The virus is adapted to bat immune systems, where it evolved to suppress the immune defenses (interferons) that mammals use to tell that they are infected. In humans, the virus can apparently spread effectively in the body with a delay in the production of symptoms and the initiation of immune responses. This delay may then promote overactive immune responses, when the virus is detected, that damage the body as a side effect. Older people are more vulnerable to the virus because they are less adapted to novel infectious agents, and invest less in immune defense, compared to younger people. Genes that increase risk of mortality from SARS-CoV-2 are functionally associated with a drug called amlodipine, which may represent a useful treatment.

Project description:New universal prophylactic vaccine platforms are needed to prevent or reduce the impact of future respiratory viral infections. While the attribute of T memory cells is particularly attractive in the context of vaccine design for viral infection, the efficiency of T and B memory cell-mediated protection generated under the adenoviral vector was tested. We studied the mechanism using the platform/ immunological factor combination (AdV1+rRBD): adenovirus AdV1 (adjuvant) armed with inducible co-stimulator ICOS and CD40 ligand in combination with recombinant spike protein rRBD (antigen) to promote the differentiation of memory T and B cells. Additionally, adenovirus AdV2 (adjuvant) without ICOS and CD40 ligand in combination with rRBD was tested. Investigating ex vivo T cell responses to the platform-specific stimuli, we found higher frequencies of CD8+ than CD4+ platform-specific T cells vs mock. The cytometric analysis showed that T cells confer protection against SARS-CoV-2 via elevated T cell subsets: CD8+TEMRA (57.6% ± SD 3.3 vs mock 39.6% ± SD 4.83) and CD4+TNAÏVE (59.6% ± SD 0.4 vs mock 50.8% ± SD 1.9). We found that CD8+TEM, CD8+TSCM, and CD8+TCM are antigen-experienced subpopulations generated via the platform after 7 days. When stimulated with the immunological factors, B cells changed from the production of IgM and IgD to isotype IgG. The CD40 gene was significantly expressed (RT-qPCR) in VERO E6 after stimulation with the platform. RNA-seq profiling identified Th1, Th2, and Th17 cell differentiation gene expression patterns that effectively protect against different pathogens. RNA-seq analysis determined signaling pathways that control immunological mechanisms by which the platform induces protective immunity: MAPK cascade, adipocytokine, cAMP, TNF, and Toll-like receptor (TLR) signaling pathway. The formulation (AdV1+rRBD) increased the production of IL-6, IL-8, and TNF vs the mock (P<0.0001). The whole-genome sequencing of VERO E6 showed differences in the expression of apoptosis gene stimulated with the platforms vs mock. Moreover, apoptotic hallmarks were identified and quantified using flow cytometry. We proved that immunogenic factors compromised plasma membrane integrity (RNA-seq). To sum up, the proposed adenoviral platform generated innate and adaptive immunity for the complex and robust regulatory system to prevent SARS-CoV-2 infections.

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Insights into the evolutionary and prophylactic analysis of SARS-CoV-2: A review.

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