SM04690 for COVID-19

Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant pneumonia in December 2019, the cumulative number of infected people worldwide has exceeded 670 million, with over 6.8 million deaths. Despite the marketing of multiple series of vaccines and the implementation of strict prevention and control measures in many countries, the spread and prevalence of SARS-CoV-2 have not been completely and effectively controlled. The latest research shows that in addition to angiotensin converting enzyme II (ACE2), dozens of protein molecules, including AXL, can act as host receptors for SARS-CoV-2 infecting human cells, and virus mutation and immune evasion never seem to stop. To sum up, this review summarizes and organizes the latest relevant literature, comprehensively reviews the genome characteristics of SARS-CoV-2 as well as receptor-based pathogenesis (including ACE2 and other new receptors), mutation and immune evasion, vaccine development and other aspects, and proposes a series of prevention and treatment opinions. It is expected to provide a theoretical basis for an in-depth understanding of the pathogenic mechanism of SARS-CoV-2 along with a research basis and new ideas for the diagnosis and classification, of COVID-19-related disease and for drug and vaccine research and development.

AbstractUnderstanding how viruses affect cellular pathways during infection may facilitate development of host cell-targeted therapeutics with broad-spectrum antiviral activity. The interferon (IFN) response is critical for reducing replication and pathogenesis of many viruses including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. Mounting evidence indicates that peroxisomes which are best known as metabolic organelles, function in the IFN response. Recently, we reported that the Wnt/β-catenin signaling pathway strongly suppresses peroxisome biogenesis. Here, we show that SARS-CoV-2 infection activates Wnt/β-catenin signaling and hypothesized that pharmacological inhibition of this pathway would result in increased peroxisome formation and enhanced IFN production. Indeed, Wnt/β-catenin signaling potently inhibits replication of SARS-CoV-2 and other pathogenic RNA viruses in vitro and reduces viral load, inflammation and clinical symptoms in a mouse model of COVID-19. As such, targeting this cellular pathway may have prophylactic and/or therapeutic value in reducing the disease burden caused by emerging viral pathogens.