Structural biology of SARS-CoV-2 leader protein (nsp1)

Following infection, SARS-CoV-2's leader protein nsp1 is the very first viral protein to be expressed. Its sequence is highly conserved among different SARS-CoV-2 strains, indicating its vital function that makes it a promising target for drugs and vaccination. Nsp1 takes over the host cell protein expression machinery to facilitate the production of SARS-CoV-2 virions by the host cell by binding to the ribosome and obstructing the expression of any but the viral proteins. To date, 28 structures obtained by cryo-electron microscopy and X-ray diffraction have been published, showing the protein's structural features as well as a number of interactions with host ribosomes. Nsp1 has also been shown to interfere with immune response pathways and is connected to the cytokine storm causing organ damage and failure in COVID-19 patients.