Subgroup Contributed Talks

eSMB2020 eSMB2020 Follow Tuesday at 1:30pm EDT
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Esteban Abelardo Hernandez Vargas

Universidad Autonoma de Mexico (UNAM)
"In-host Mathematical Modelling of COVID-19 in Humans"
COVID-19 pandemic has underlined the impact of emergent pathogens as a major threat for human health. The development of quantitative approaches to advance comprehension of the current outbreak is urgently needed to tackle this severe disease. In this talk, mathematical models will be introduced to represent SARS-CoV-2 dynamics in infected patients. Considering different starting times of infection, parameters sets that represent infectivity of SARS-CoV-2 are computed for the target cell limited model and compared with other viral infections that can also cause pandemics. The best model to fit the data was including immune cell response, which suggests a slow immune response peaking between 5 to 10 days post onset of symptoms. The model with eclipse phase, time in a latent phase before becoming productively infected cells, was not supported. Interestingly, both, the target cell limited model and the model including immune responses, predict that SARS-CoV-2 may replicate very slowly in the first days after infection, and it could be below detection levels during the first 4 days post infection. These models can serve for future evaluation of control theoretical approaches to tailor new potential drugs against COVID-19.

(CANCELLED) Christopher Rowlatt

University of St Andrews
"(CANCELLED) Modelling the within-host spread of SARS-CoV-2 infection, and subsequent immune response, using a hybrid multi-scale individual-based model"
The coronavirus 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide. A dysfunctional immune response, and the interaction with secreted cytokines (cytokine storm), has been observed to correlate with disease severity. However, the precise mechanisms which lead to disease severity remain unclear. In this talk, we employ a hybrid multi-scale individual-based model to study the spread of SARS-CoV-2 on an epithelial monolayer, its interaction with the host immune response and the immune cell cross-talk, as well as the interaction with secreted cytokines.

Rajat Desikan

Indian Institute of Science Bangalore
"Targeting TMPRSS2 and Cathepsin B/L together may be synergistic against SARS-CoV-2 infection"
The entry of SARS-CoV-2 into target cells requires the activation of its surface spike protein, S, by host proteases. The host serine protease TMPRSS2 and cysteine proteases Cathepsin B/L can activate S, making two independent entry pathways accessible to SARS-CoV-2. Blocking the proteases prevents SARS-CoV-2 entry in vitro. This blockade may be achieved in vivo through ‘repurposing’ drugs, a potential treatment option for COVID-19 that is now in clinical trials. Here, we found, surprisingly, that drugs targeting the two pathways, although independent, could display strong synergy in blocking virus entry. We predicted this synergy first using a mathematical model of SARS-CoV-2 entry and dynamics in vitro. The model considered the two pathways explicitly, let the entry efficiency through a pathway depend on the corresponding protease expression level, which varied across cells, and let inhibitors compromise the efficiency in a dose-dependent manner. The synergy predicted was novel and arose from effects of the drugs at both the single cell and the cell population levels. Validating our predictions, available in vitro data on SARS-CoV-2 and SARS-CoV entry displayed this synergy. Further, analysing the data using our model, we estimated the relative usage of the two pathways and found it to vary widely across cell lines, suggesting that targeting both pathways in vivo may be important and synergistic given the broad tissue tropism of SARS-CoV-2. Our findings provide insights into SARS-CoV-2 entry into target cells and may help improve the deployability of drug combinations targeting host proteases required for the entry.

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Virtual conference of the Society for Mathematical Biology, 2020.