Exploring COVID-19 Infectious Mechanisms and Host Selection Process

Exploring COVID-19 Infectious Mechanisms and Host Selection Process is led by Prof. Modesto Orozco from the Institute for Research in Biomedicine (IRB Barcelona), Spain. The main goal of Orozco's team is to understand the evolutionary path driving the virus from a bat to humans, to forecast human sensitivity to infection, and the impact of the virus mutations on the infectivity. Also, they aim to predict new variants of the virus emerging in a second wave and their potential for infectivity. With 93% identity, the COVID-19 RNA sequence is similar to a virus found in horseshoe bats (Rhinolophus Anis), but how this virus jumped to humans is unclear. Deciphering the pathways it took is key to avoid the emergence of new infections, which are in a cryptic state in other exotic animals. The scientists aim to anticipate the virus' next move and clarify the pathway. They want to know its mutational space, understand varying susceptibility to infection, and predict genomic changes, impacting infectiveness. The group plans molecular dynamics (MD) simulations to provide information on potential cavities in the variants of viral proteins which can be tackled by drugs. To achieve this, the team involves four computational groups (N. López-Bigas and M. Orozco at IRB, and R. Badia and J.L. Gelpí at Barcelona Supercomputing Center) and experimental groups in Marseille and Milan. They will focus on the entrance of the virus into the human cell by binding the Spike protein to human cell receptor ACE2 and perhaps to protein CD147. The group estimated that ± 80% of the mutations impacting infection are located in the receptor-binding region of the Spike. It is unclear how the virus will mutate when specific drugs or antibodies attack it. Or if the virus' proofreading protein will be fully inactivated. Through HPC study an in-depth analysis was made of mutations and potential future mutations, ranking those that are more likely to happen. PRACE awarded the project with 6 000 000 core hours on Joliot-Curie Rome, hosted by GENCI at CEA, France.