Periodic Reporting for period 2 - RNAVirFitness (The dark side of evolution: the deleterious mutational landscape of RNA viruses)
Periodo di rendicontazione: 2021-12-01 al 2023-05-31
The objectives of this project are to use a combination of computational and experimental approaches to investigate how mutations impact the ability of viruses to replicate. First, we aim to compare different viruses: are there basic rules that govern virus evolution? For example, are there regions of virus genomes where mutations always have a deleterious impact? This will allow us to discover the “Achilles-heel” of viruses, and this could potentially allow generating therapeutics that target this weak spot. Next, we aim to understand how combinations of mutations affect genomes of viruses. Thus, for example, one mutation may be deleterious on its own, but when two mutations occur together, they might become beneficial to the virus. It is critical to understand how this happens, since such combinations may lead to viruses that are more transmissible or more virulent. Finally, our goal is to understand if and how the effects of mutations differ in different environments. For example, a mutation may have a deleterious impact when a virus replicates in the lungs but may have a different impact when the virus replicates in upper airways. Overall, our goal is to generate comprehensive understanding of the impact of mutations across a wide range of different viruses.
Beyond SARS-Coronavirus-2, which has naturally been a focus of research in the past few years, we have also made some leaps forward in our understanding of a completely different virus, called MS2. This virus attacks bacteria and is also a very fast evolving virus. We were able to infer the rate of mutation and the impact of different mutation on the viral genome. Interestingly, we were able to show that pairs of mutation behave differently from each mutation on its own. This is a first and important step in both of the first main goals of this project.
We expect to continue obtaining insights into SARS-Coronavirus-2 with the aim of obtaining a better understanding of how variants are formed and how they evolve. We moreover plan to compare this to other viruses and their routes of evolution.