PepTalk: The Spike's Significant Sequence?

The Spike's Significant Sequence?

Arg-Gly-Asp (RGD) peptides are of interest in numerous therapeutic areas such as cancer, angiogenesis, antithrombosis, and more. RGDs are found naturally in several places, including within bone sialoprotein (SGP), transforming growth factor beta (TGFß), in cell adhesive extracellular matrix (ECM) proteins, and as disintegrins in viper venoms, to name a few. The sequence also happens to be contained within the spike protein (S protein) of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Important for binding to the RGD-integrins, the sequence is a cell attachment site for many proteins and is involved in many cell processes including cell proliferation and differentiation.1

https://www.pepnet.com/res/uploads/media//Arginylglycylaspartic_acid.pngThe RGD structure

Like other coronaviruses, SARS-CoV-2 uses its spike proteins to gain entry into host cells. Angiotensin converting enzyme 2 (ACE2) and serine protease type II transmembrane serine protease (TMPRSS2) are two locations of entrance. A few interesting new publications highlight that, with an RGD-sequence on its S protein, there is a possibility that SARS-CoV-2 may also use the integrins to gain cell entry. The tripeptide is located within the section of the receptor binding domain that binds to human ACE2 (amino acids 437-508). Other types of viruses use integrin binding, so it is not unusual for SARS-CoV-2 to have it within its arsenal. Blocking integrin binding may be a viable route for neutralizing the virus.2,3

References:

  1. C.-C. Sun, X.-J. Qu, & Z.-H. Gao, American Journal of Therapeutics, 23, e198 (2016). Abstract retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24621642
  2. A Potential Role for Integrins in Host Cell Entry by SARS-CoV-2.
  3. An Evolutionary RGD Motif in the Spike Protein of SARS-CoV-2 May Serve as a Potential High Risk Factor for Virus Infection? (pre-print)

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