Comparative efficacy of antiviral strategies targeting different stages of the viral life cycle: A viral quasispecies dynamics study

Abstract

While the COVID-19 pandemic continues to impact public health worldwide significantly, the use of antiviral drugs and therapies has dramatically reduced the instances of severe disease and death. More broadly, the unprecedented use of antivirals also provides hope for preventing and mitigating similar viral outbreaks in the future. Here we ask: What are the comparative impact of antiviral therapeutics targeting different stages of the viral lifecycle? How do antiviral therapeutics impact the viral population in the bloodstream, or in other words, the viral load in high and low-immunity individuals? To address these questions, we use a model of viral quasispecies dynamics to examine the efficacy of antiviral strategies targeting three critical aspects of the viral life cycle, fecundity, reproduction rate, or infection rate. We find a linear relationship of the viral load with the change in fecundity and a power law with the change in the reproduction rate of the virus, with the viral load decreasing as the fecundity and the reproduction rates are decreased. Interestingly, however, for antivirals that target the infection rate, the viral load changes non-monotonically with the change in infection rate; the viral population initially increases and then decreases as the infection rate is decreased. The initial increase is especially pronounced for individuals with low immunity. By examining the viral population inside cells for such cases, we found that the therapeutics are only effective in such individuals if they stop the infection process entirely. Otherwise, the viral population inside cells does not go extinct. Our results predict the effectiveness of different antiviral strategies for COVID-19 and similar viral diseases and provide insights into the susceptibility of individuals with low immunity to effects like long covid.