Minisymposium lectures

Understanding the efficacy of capsid protein allosteric modulators using a multiscale model of hepatitis B virus

Sarafa Iyaniwura

true  Friday, 11:00 ! Ongoingin  Schultz Theatrefor  30min

As the search for a cure for the Hepatitis B virus (HBV) continues, pharmaceutical companies have continued to develop drugs that target different stages of the intracellular life-cycle of the virus. The earlier developed drugs, the nucleoside reverse transcriptase inhibitors (NRTIs) analogues, have been shown to be effective in suppressing HBV viral load (VL) in patients with chronic infection. However, these drugs need to be taken for a lifetime to maintain VL suppression, creating the risk of adverse effects and the emergence of drug-resistant strains of the virus. The development of a new class of drugs, the capsid protein allosteric modulators (CpAMs), has created renewed hope for finding a functional cure for HBV. These drugs inhibit the encapsidation of polymerase-pregenomic RNA (pgRNA) in infected cells. We developed a multiscale age-structured model of HBV. Our model incorporates the intracellular and extracellular dynamics of HBV RNA and DNA and keeps track of the age of infection of infected hepatocytes. We derived an equivalent ODE system for our multiscale model and fitted the reduced model to the viral loads of chronic HBV patients treated with CpAMs and NTRIs, to understand the efficacies of the drugs.

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