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Vaccines Against COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Majid Khan, Muhammad Faheem, Najmur Rahman, Rizwan Ahmad, M. Zia-Ul-Haq, Muhammad Ria
Precise mechanisms between the host receptors and the virus surface proteins are crucial for understanding host tropism, cross-species diffusion, and establishing animal models to develop vaccines [32]. The S-protein of coronaviruses (CoVs) is an essential target for developing a vaccine because it joins the infection mechanism via receptor binding of the host cells. Spike protein of coronavirus identifies different host receptors (SARs utilizes ACE2 as a receptor). The S1-subunit possesses a receptor-binding domain whereas, the S2 is essential for fusion with the membrane of viruses and host cells [31, 32].
Population Dynamics of Pathogens
Published in Leonhard Held, Niel Hens, Philip O’Neill, Jacco Wallinga, Handbook of Infectious Disease Data Analysis, 2019
Population dynamics of pathogens is the description of how incidence of infectious agents varies in space and time, and the host and pathogen factors responsible for this variation. “Pathogens” is a catch-all term for small, typically the size of a single cell or smaller, organisms with a parasitic life-style that cause sickness and/or death of its host and requires onwards transmission for continued persistence. Some pathogens — the “directly transmitted” — achieve this by moving directly from host to host without any specialized transmission stages, either via a respiratory, fecal-oral, or sexual route. Others — the “vector-borne” — have complicated life-cycles involving biting arthropods to complete the infection cycle. Pathogens further differ with respect to host tropism. Some appear only able to infect a single host species while others have a wide host range [1]. Given that parasitism is arguably the most common consumer strategy across the tree of life [2], pathogen population ecology is a vast area of study. Moreover, because of the great importance of pathogens in history, economics, food production, public health, and human/animal well-being, students of this topic use tools from a variety of disciplines including statistics and mathematics. The purpose of this chapter is to give an introduction to the diverse dynamics of infectious disease agents and visit on some of the mathematical and statistical methods used to characterize and understand these. Much of what is sampled here is the detailed focus of other chapters in this handbook.
SARS-CoV-2 Morphology, Genomic Organisation and Lifecycle
Published in Srijan Goswami, Chiranjeeb Dey, COVID-19 and SARS-CoV-2, 2022
Srijan Goswami, Ushmita Gupta Bakshi
The spike (S) protein of SARS-CoV-2, the most outward envelope protein, is a glycosylated transmembrane structure, made up of 1162 to 1452 amino acid residues. The spike protein facilitates the attachment of SARS-CoV-2 with the receptors on the host cell membranes, leading to the fusion of the two structures. The spike protein of SARS-CoV-2 is not only responsible for the tropism of the virus but also aids in the induction of the host immune response (Masters, 2006; Hulswit et al., 2016Li, 2016; Tortorici & Veesler, 2019). Tropism is the ability of a pathogenic microorganism to infect a particular host (host tropism) (McFadden et al., 2009). This makes the spike protein a structure of medical concern. Based on topology, the spike protein can be divided into three basic regions (domains). These are the cytoplasmic domain, the helical (transmembrane) domain and the extracellular domain. The cytoplasmic domain, also known as the endodomain or the intracellular tail, presents at the virion interior (residues 1235–1273, UniProtKB – P0DTC2, n.d.). The helical (transmembrane) domain consists of only a small N-terminal segment (residues 1214–1234, UniProtKB – P0DTC2, n.d.). The extracellular domain, also known as the Ectodomain, presents at the virion exterior (residues 13–1213, UniProtKB – P0DTC2, n.d.) (Masters, 2006; Li, 2016). Apart from that, the fundamental structure of the spike protein can be divided into two major subunits, S1 and S2. Subunit 1 (S1) also known as the receptor-binding domain, helps coronaviruses bind to host cell receptors (UniProtKB – P59594, n.d.; Hulswit et al., 2016; Tortorici & Veesler, 2019). The receptor-binding domain (RBD) of SARS-CoV-2 recognises a specific receptor known as the angiotensin converting enzyme receptor-2 (ACE-2). These ACE-2 receptors are located in the lungs, heart, kidneys and intestines inside the human body. The affinity of the RBD of SARS-CoV-2 for ACE-2 has been found to be 20 times higher as compared with a normal SARS virus. This increased affinity makes SARS-CoV-2 a global concern. The second functional portion, known as subunit 2 (S2) (as shown in Figure 2.2), mediates the fusion reaction between the virus and the host cell membrane. Subunit 2 can be considered as a class I viral fusion protein having a fusion peptide (FP), heptad repeat 1 (HR1), a central helix (CH), a connector domain (CD), heptad repeat 2 (HR2), a transmembrane domain (TM) and a cytoplasmic tail (CT) (UniProtKB – P59594, n.d.; Hulswit et al., 2016; Tortorici & Veesler, 2019) (Figure 2.3).
COVID-19 during Pregnancy and Postpartum:
Published in Journal of Dietary Supplements, 2022
Sreus A. G. Naidu, Roger A. Clemens, Peter Pressman, Mehreen Zaigham, Kamran Kadkhoda, Kelvin J. A. Davies, A. Satyanarayan Naidu
CoVs have a remarkable potential to change host tropism. The divergent mechanisms by which CoVs enter host cells, and subsequently spread intercellularly, may explain the remarkable transmission of these viral pathogens into new hosts, including humans (Hulswit et al. 2016). The tremendous pandemic potential of CoVs was proven in the past two decades by three global outbreaks of deadly pneumonia: the SARS-CoV, the MERS-CoV and the ongoing SAR-CoV-2 pandemic. One of the primary determinants of CoV tropism is the spike (S) protein for viral entry. Trimers of the S-protein facilitate the initial steps of viral pathogenesis: i) viral docking to a cell surface receptor (CSR) and ii) fusion of the viral and cellular membrane. Interestingly, S-protein also contains the principal antigenic domains and is the target of neutralizing antibodies. The prevalence of community acquired CoVs, immunizations with CoV/influenza vaccines with shared antigenic epitopes, and the consequential anamnesis may lead to “original antigenic sin (OAS)” (Kadkhoda 2020; Roncati and Palmieri 2020). Considering the inherent genetic flexibility of CoV S-proteins, it is possible that new outbreaks with novel viral mutants or their genetic variants may emerge in the future.
COVID-19 during Pregnancy and Postpartum:
Published in Journal of Dietary Supplements, 2022
Sreus A. G. Naidu, Roger A. Clemens, Peter Pressman, Mehreen Zaigham, Kelvin J. A. Davies, A. Satyanarayan Naidu
The SARS-CoV-2 has acquired a unique polybasic cleavage site (R-R-A-R) at the junction of S1 and S2, which facilitates an effective cleavage by furin and other proteases (Andersen et al. 2020). This novel virulence trait has significantly enhanced the infectivity, host tropism, and pathobiological spectrum of COVID-19 (Nao et al. 2017). Competitive blocking of SARS-CoV-2 polybasic cleavage site with highly basic innate host proteins or peptides with a stretch of arginine residues may serve as a viral intervention strategy. Milk LF inhibits HIV and the antiviral activity correlates with the negative charge (polybasic arginine residues) on the N-terminal region of LF protein (Swart et al. 1999). Interestingly, LF also demonstrates serine protease activity and cleaves arginine-rich sequences in a variety of microbial virulence proteins, contributing to its long-recognized antimicrobial properties (Hendrixson et al. 2003).
In quest of a new therapeutic approach in COVID-19: the endocannabinoid system
Published in Drug Metabolism Reviews, 2021
Ondine Lucaciu, Ovidiu Aghiorghiesei, Nausica Bianca Petrescu, Ioana Codruta Mirica, Horea Rareș Ciprian Benea, Dragoș Apostu
SARS-CoV-2 belongs to the Coronavirinae family, presenting the largest genome among RNA viruses. This virus is an enveloped, positive-sense RNA virus, with spike-like projections on the surface (Jin et al. 2020). Viral replicase/transcriptase function is encoded in two-thirds of the genome, while the other third encodes viral structural proteins. The genome is packed into a helical nucleocapsid protected by a lipid bilayer. Based on their genomic structure, Coronaviruses are divided into four groups: α, β, γ, and δ. The first two types of coronaviruses infect only mammals (Rabi et al. 2020). SARS-CoV-2 is a β coronavirus. Four proteins are present in coronaviruses: nucleocapsid (N), envelop (E), membrane (M), and spike (S). The last-mentioned protein determines the host tropism, being the leading mediator of viral entry and it is formed out of transmembrane trimetric glycoprotein (Bosch et al. 2003). This protein has two subunits: S1 and S2, S1 is responsible for the process of binding to the host cell, and S2 for the fusion of the cell and virus membrane. Li et al. 2003 demonstrated that Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for the SARS coronavirus. ACE2 is a type I integral membrane protein, a mono-carboxypeptidase that hydrolyzes angiotensin II. This protein is highly expressed on lung epithelial cells, in the heart, ileum, kidneys, and bladder (Zou et al. 2020).