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Framework of multiscale model of SARS-CoV-2 infection.

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posted on 24.11.2021, 18:34 by Shun Wang, Mengqian Hao, Zishu Pan, Jinzhi Lei, Xiufen Zou

Intracellular: The S protein of SARS-CoV-2 binds to receptor proteins (ACE2, NRP1) on the cell surface. Viral dynamics within a target cell are considered, which include (1) the release of RNA of SARS-CoV-2, (2) virus-activated IFN expression, (3) positive feedback of IFNs, (4) activation of AVPs by IFNs, (5) natural depletion of IFNs, (6) inhibition of the virus by AVPs, (7) viral RNA replication, (8) protein synthesis, assembly of novel SARS-CoV-2 and budding into the extracellular environment, (9) natural degradation of AVPs, and (10) degradation of viral RNA. The progeny viruses leave the target cell by budding and further infect additional susceptible cells. Intercellular: The status of target cells is divided into uninfected and infected. There is a supplied source of normal cells that will be transformed into infected cells if they are infected by the virus. The infected cell is identified and cleaned by effector T cells. With respect to cellular communication, T cells mediate the immune response to SARS-CoV-2. PRRs on the cell surface sense SARS-CoV-2 and activate the immune response. Immune cells secrete cytokines, such as IL-6, IL-10, IFN-γ, etc., and activate naïve T cells. The activated T cells undergo differentiation and proliferation, and emerge as effector T cells. Activated T cells and effector T cells clear the infected cells and secrete cytokines. Some of cytokines (pro-inflammatory cytokines) induce chronic inflammation, dysfunction of the immune response, and exhaustion of the effector T cells, which contribute to disease progression. Organism: The population size of infected cells dictates the progression and severity of COVID-19. The progression of COVID-19 is divided to two phases, symptomatic and asymptomatic. Furthermore, the severity of symptomatic patients is primarily divided into mild-moderate and severe.