In a combined work effort over 20 research labs scientists compiled a map of the global phosphorylation landscape of SARS-CoV-2 infection. Bouhaddou et al monitored SARS-CoV-2 infection in Vero E6 cells via quantitative mass spectrometry-based phosphoproteomics.¹ They observed a major impact on phosphorylation on host and viral proteins, leading to the identification of new potential drugs which target dysregulated pathways and provide strong antiviral efficacy.
Changes in phosphorylation reflect altered activities of kinases that are hijacked during the infection to influence cellular signaling. This kinases represent ideal drug targets. The most strongly regulated kinases fall into a set of signaling pathways that include p38/MAPK signaling, AKT and ERK signaling, CK2 cytoskeleton signaling, and cell cycle regulation (fig 1.). CK2 and p38 MAPK are promoted while mitotic kinases are shutdown, resulting in cell cycle arrest. We offer antibodies, proteins and kits for further investigation on these targets.
Fig. 1: Kinase acitivty after infection.¹ Kinases depicting a strong change in activity upon infection (abs(log10(p)) > 2.5) in at least one time point, with predicted activity in at least 5 of 6 time points
Based on changes in phosphorylation the team estimates changes in activity in a total of 97 human kinases. Several drugs and compounds which are already FDA approved, or in clinical testing showed antiviral activity, including silmitasertib (CK2, phase II), Ggilteritinib (AXL, FDA approved), ARRY-797 (p38, phase 2/3), MAPK13-IN-1 (p38, preclinical), SB203580 (p38, preclinical), ralimetinib (p38, phase 2), apilimod (PIKFYVE, phase 1), and dinaciclib (CDK, phase 3). This new insights help to further understand COVID-19 infections and find improved therapeutic strategies but further research is necessary. Discover our SARS-CoV-2 antbodies, proteins and kits down below.