Understanding individual SARS-CoV-2 proteins for targeted drug development against COVID-19

Abstract

SARS-CoV-2 causes the COVID-19 pandemic responsible for millions of deaths globally. Even with effective vaccines, the SARS-CoV-2 virus will likely maintain a hold in the human population through gaps in efficacy and vaccination and arising new strains. Therefore, understanding how SARS-Cov-2 causes such wide-spread tissue damage and developing targeted pharmacological treatments will be critical in fighting this virus and preparing for future outbreaks. Herein, we summarize the progress made thus far by using in vitro or in vivo models to investigate individual SARS-CoV-2 proteins and their pathogenic mechanisms. We grouped the SARS-CoV-2 proteins into three categories: host-entry, self-acting and host-interacting. This review focuses on the self-acting and host-interacting SARS-CoV-2 proteins and summarizes current knowledge on how these proteins promote virus replication and disrupt host systems, as well as drugs that target these virus- and interacting host proteins. Many of these drugs are currently in clinical trials for the treatment of COVID-19. Future coronavirus outbreaks will mostly likely be caused by new virus strains that evade the vaccines through mutations in host-entry proteins. Therefore, study of individual self-acting and host-interacting SARS-CoV-2 proteins for targeted therapeutic interventions is not only essential for fighting COVID-19, but also valuable against future coronavirus outbreaks.