Covid-19 simulations at cellular level for in silico drug trials

The applied mathematics researchers are using in silico experiments to replicate in great detail how the human immune system responds to the novel coronavirus. This refers to trials carried out via computer simulations, rather than in vitro or in vivo experiments situated in test tubes or in living organisms; in silico trials are a complement to these real-world trials.

“It’s not that in silico trials should replace clinical trials,” said Professor Anita Layton, who holds a chair in mathematical biology and medicine. “A model is a simplification, but it can help us whittle down the drugs for clinical trials. Clinical trials are expensive and can cost human lives. Using models helps narrow the drug candidates to the ones that are best for safety and efficacy.”

Their model describes the control of a coronavirus infection by the innate and adaptive immune components at the cellular level. Invasion by the virus triggers innate immunity, through which the target cells become resistant to infection, and infected cells are removed. The adaptive immune response, meanwhile, is represented by plasma cells and virus-specific antibodies.

The University of Waterloo team is among the first to be working on these models, being able to capture the results of different treatments that were used in Covid-19 patients in clinical trials. Their results were very consistent with live data on real infections and treatments.

Among the treatments they simulated was Remdesivir: a drug used in the WHO’s global “solidarity” trials. The simulation and the live trial both showed the drug to be biologically effective but clinically questionable, unless administered very soon after infection by the coronavirus. They also applied the model to simulate use of convalescent plasma transfusion therapy and a hypothetical therapy which works by inhibiting viral entry into host cells.

For all three therapies, they must be administered no more than two days after the onset of Covid-19 symptoms.

Their model may be well-suited to rapidly testing treatments’ effectiveness against viral variants of concern: both current variations such as the highly transmissible Delta variant and future variants. The development and demonstration of the model has been reported in Viruses.

“As we learn more about different variants of concern, we can change the model’s structure of parameters to simulate the interaction between the immune system and the variants,” said PhD candidate Mehrshad Sadria. “And we can then predict if we should apply the same treatments or even how the vaccines might work as well.”