Multi-omics study revealing putative drug targets of COVID-19 severity and other viral infection diseases

Drug target prioritization for new targets and drug repurposing of existing drugs for COVID-19 treatment are urgently needed for the current pandemic. COVID-19 drugs targeting human proteins will potentially relate to different host responses involving multiple molecular pathways. Here we implemented a novel COVID-19 drug target prioritisation protocol by integrating multi-omics Mendelian randomization (MR) of COVID-19 severity with colocalization. By integrating novel MR and existing evidence, we prioritised 353 candidate drug targets with clinical and/or literature evidence of host-coronavirus interaction and one additional target (ENTPD5) with robust MR and colocalization evidence on COVID-19 severity. We further conducted phenome-wide MR of these prioritised targets on 622 complex diseases in 11 SARS-CoV-2 related tissues, which we identified 726 potential causal effects on other diseases, providing information on potential beneficial and adverse effects. This study demonstrated the value of our integrative approach in prioritising drug targets and mechanisms involved in COVID-19 severity. This provides the first steps towards evaluating intervention targets worthy of follow-up for coronavirus and viral infections.Integrating multi-omic evidence to prioritise potential drug targets and identify molecular mechanisms for COVID-19 severity.