General information on Growth factor-like peptide
Nonstructural protein 10, also known as growth factor like, GFL and nsp10 is a macromolecule that plays a pivotal role in viral transcription. By definition, a nonstructural protein is a protein encoded by a virus but is not part of the viral structure. Nonstructural proteins typically include various transcript factors and enzymes that are key for both virus replication as well as controlling the biological mechanisms within the host cell. Similar to the other 16 ‘nonstructural’ proteins, nsp10 is generated from the cleavage of replicase polyproteins 1a and 1ab encoded by the open reading frame of the viral genome. Among these, nsp10 stimulated both nsp14 3′-5′ exoribonuclease and nsp16 2′-O-methyltransferase activities. As such, nsp10 is also involved in viral messenger RNA cap methylation. GFL protein is considered as a potential target for the development of safe vaccine against severe acute respiratory syndrome coronavirus (SARS-CoV). The latter is a highly contagious disease that affects epithelial respiratory cells and is responsible for coronavirus diseases (COVID).
Nsp10 protein contains one domain which consists of a pair of antiparallel N-terminal helices arranged around an irregular β-sheet, a coil-rich C terminus and two zinc fingers. The presence of two zinc fingers along with a large positively charged patch located on the surface of GFL protein is believed to facilitate RNA-binding. The first zinc finger belongs to a new zinc finger family. As such, nsp10 is the first structural representative of this zinc finger family which is exclusively located in coronaviruses. Furthermore, the growth factor like protein adopts a tertiary fold structure that has not been observed before. Nsp10 protein interacts several other viral proteins of COVID virus more precisely nsp1, nsp2, nsp5, nsp7, nsp8, nsp9, nsp12, nsp13 and sars9a. It is believed that the protein also interacts with oxidoreductase system in mitochondria which contributes to the cytopathogenic effect of COVID infection in the lungs.