Progress in molecular biology and translational science最新文献

The administration of therapeutic proteins directly to the eye is a major breakthrough in the treatment of several eye conditions. This chapter highlights the crucial significance of ocular therapies because of the widespread occurrence of vision-threatening disorders and the distinct difficulties presented by the eye's architecture and physiological limitations. Therapeutic proteins, known for their exceptional specificity and effectiveness, provide hopeful answers. However, they encounter various obstacles in their ocular distributions like tear film, corneal epithelium, and blood-retinal barrier etc. Formulation techniques and drug delivery technologies, such as nanotechnology, hydrogels, microneedles, liposomes, dendrimers, and polymeric nanoparticles are improving the stability, bioavailability, and targeted administration of proteins. Notwithstanding this progress, obstacles such as protein stability, immunogenicity, and patient compliance endure. Methods to address these challenges include improving permeability, formulating sustained release systems, applying non-invasive delivery techniques, and implementing tailored delivery strategies. Furthermore, it is essential to effectively navigate through regulatory routes, comprehensively grasp market factors, and successfully secure intellectual property to achieve successful commercialization of these new methods.

This chapter discusses the SARS-CoV-2 variants and their immune evasion strategies, shedding light on the dynamic nature of the COVID-19 pandemic. The ecological dynamics and viral evolution of SARS-CoV-2 are explored, considering carriers of infection, individual immunity profiles, and human movement as key factors in the emergence and dissemination of variants. The chapter discusses SARS-CoV-2 mutation, including mutation rate, substitution rate, and recombination, influencing genetic diversity and evolution.

Transmission bottlenecks are highlighted as determinants of dominant variants during viral spread. The evolution phases of the pandemic are outlined, from limited early evolution to the emergence of notable changes like the D614G substitution and variants with heavy mutations. Variants of Concern (VOCs), including Alpha, Beta, Gamma, and the recent Omicron variant, are examined, with insights into inter-lineage and intra-lineage dynamics. The origin of VOCs and the Omicron variant is explored, alongside the role of the furin cleavage site (FCS) in variant emergence. The impact of structural and non-structural proteins on viral infectivity is assessed, as well as innate immunity evasion strategies employed by SARS-CoV-2 variants. The chapter concludes by considering future possibilities, including ongoing virus evolution, the need for surveillance, vaccine development, and public health measures.

This chapter provides a detailed exploration of the epidemiology of COVID-19, focusing on several key aspects that offer valuable insights into the disease progression. A comprehensive comparison is made between the three related coronaviruses: SARS-CoV, MERS-CoV, and SARS-CoV-2, elucidating their similarities and differences in terms of transmission dynamics, clinical presentation, laboratory and radiological findings, infection mechanisms, and mortality rates. The concept of herd immunity is then discussed, exploring its relevance and potential implications for controlling the spread of COVID-19. Next, the chapter delves into the changing epidemiology of the disease, examining how various factors such as human behavior, public health interventions, and viral mutations have influenced its transmission patterns and severity over time. Finally, the timelines and evolution of COVID-19 are outlined, tracing the origins of the virus, its rapid global spread, and the emergence of new variants.

This chapter provides a comprehensive overview of the techniques employed to unravel the structural biology of SARS-CoV-2, facilitating a deeper understanding of the virus for developing future therapeutic strategies. Various techniques such as Electron microscopy (EM) for capturing high-resolution images of the virus and X-ray crystallography used for determining atomic-level structures of viral proteins are discussed. Cryo-electron microscopy (cryo-EM) imaging is also examined as a powerful tool for visualizing the virus's structure in its native state. Intracellular detection and tracking of SARS-CoV-2 are discussed, highlighting the techniques employed to study the virus's behavior within host cells. The chapter further explores how cryo-EM has been instrumental in delivering high-quality structural information on SARS-CoV-2, enabling researchers to better understand its mechanisms of infection and replication. The structural visualization of SARS-CoV-2 is then presented, focusing on key components such as the spike protein structure, RNA polymerase structure, and the visualization of intact and in-situ virions using cryo-electron tomography (cryo-ET). Lastly, the chapter touches upon the application of nuclear magnetic resonance (NMR) spectroscopy for studying the dynamics and interactions of viral proteins

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), refers to a constellation of persistent symptoms and health issues that continue beyond the acute phase of COVID-19. This chapter provides an overview of the pathogenesis, risk factors, manifestations, major findings, and diagnosis and treatment strategies associated with Long COVID. Hypotheses regarding the pathogenesis of Long COVID are discussed, encompassing various factors such as persistent viral reservoirs, immune dysregulation with or without reactivation of herpesviruses (e.g., Epstein-Barr Virus and human herpesvirus), dysbiosis, autoimmunity triggered by infection, endothelial dysfunction, microvessel blood clotting, and dysfunctional brainstem and/or vagal signaling. The chapter also highlights the risk factors associated with Long COVID and its occurrence in children. The major findings of Long COVID, including immune dysregulation, vessel and tissue damage, neurological and cognitive pathology, eye symptoms, endocrinal issues, myalgic encephalomyelitis and chronic fatigue syndrome, reproductive system involvement, respiratory and gastrointestinal symptoms, and the chronology of symptoms, are thoroughly explored. Lastly, the chapter discusses the challenges and current approaches in the diagnosis and treatment of Long COVID, emphasizing the need for multidisciplinary care and individualized management strategies.