Gregg, S. | bioRxiv Science

bioRxiv2023

Genetic consequences of effective and suboptimal dosing with mutagenic drugs in a hamster model of SARS-CoV-2 infection

Mutagenic antiviral drugs have shown promising results against multiple viruses, yet concerns have been raised about whether their use might promote the emergence of new and harmful viral variants. Here, we examine the genetic consequences of effective and suboptimal dosing of favipiravir and molnupiravir in the treatment of SARS-CoV-2 infection in a hamster model. We identify a dose-dependent effect upon the mutational load in a viral population, with molnupiravir having a greater potency than favipiravir per mg/kg of treatment. The emergence of de novo variants was largely driven by stochastic processes, with evidence of compensatory adaptation but not of the emergence of drug resistance or novel immune phenotypes. Effective doses for favipiravir and molunpiravir correspond to similar levels of mutational load. Combining both drugs had an increased impact on both efficacy and mutational load. Our results suggest the potential for mutational load to provide a marker for clinical efficacy.

evolutionary biology↗

bioRxiv2022

Determinants of hyena participation in risky collective action

Many species engage in risky cooperative behaviors, which pose a challenge to evolutionary theory: participants take on all the costs of cooperation, yet even non-participants benefit from success in these encounters. So, why participate in these risky behaviors? We address this question using data from spotted hyenas fighting with lions. Lions are much larger, and kill many hyenas, so these fights require cooperative mobbing by hyenas for them to succeed. We identify factors that predict: (1) when hyena groups engage in cooperative fights with lions, (2) which individuals choose to participate, and (3) how the benefits of victory are distributed among cooperators and non-cooperators. We find that cooperative mobbing is more strongly influenced by lower costs (no male lions, more hyenas) than higher benefits (need for food). Individual participation is facilitated by social factors, both over the long term (close kin, social bond strength) and the short term (greeting interactions prior to cooperation). Finally, we find some direct benefits of participation; after cooperation, participants were more likely to feed at contested carcasses than non-participants. Overall, these results suggest that, when animals play dangerous cooperative games, selection favors flexible strategies that are sensitive to dynamic factors emerging over multiple time-scales.

animal behavior and cognition↗