Targeting ATP2B1 impairs PI3K/Akt/FOXO signaling and reduces SARS-COV-2 infection and replication

ATP2B1 is a known regulator of calcium (Ca2+) cellular export and homeostasis. Diminished levels of intracellular Ca2+ content have been suggested to impair SARS-CoV-2 replication. Here, we demonstrate that a nontoxic caloxin-derivative compound (PI-7) reduces intracellular Ca2+ levels and impairs SARS-CoV-2 infection. Furthermore, a rare homozygous intronic variant of ATP2B1 is shown to be associated with the severity of COVID-19.

Inorganic polyphosphates (polyPs) are linear polymers composed of repeated phosphate (PO43−) units linked to-
gether by multiple high-energy phosphoanhydride bonds. In addition to being a source of energy, polyPs have 
cytoprotective and antiviral activities. Here, we investigated the antiviral activities of long-chain polyPs against 
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.