TY - JOUR
T1 - Peptide Inhibitors of Viral Assembly
T2 - A Novel Route to Broad-Spectrum Antivirals
AU - ElSawy, Karim M.
AU - Twarock, Reidun
AU - Verma, Chandra S.
AU - Caves, Leo S. D.
PY - 2012/3/26
Y1 - 2012/3/26
N2 - We investigated the potential of small peptide segments to function as broad-spectrum antiviral drug leads. We extracted the a-helical peptide segments that share common secondary-structure environments in the capsid protein protein interfaces of three unrelated virus classes (PRD1-like, HK97-like, and BTV-like) that encompass different levels of pathogenicity to humans, animals, and plants. The potential for the binding of these peptides to the individual capsid proteins was then investigated using blind docking simulations. Most of the extracted a-helical peptides were found to interact favorably with one or more of the protein protein interfaces within the capsid in all three classes of virus. Moreover, binding of these peptides to the interface regions was found to block one or more of the putative "hot spot" regions on the protein interface, thereby providing the potential to disrupt virus capsid assembly via competitive interaction with other capsid proteins. In particular, binding of the GDFNALSN peptide was found to block interface "hot spot" regions in most of the viruses, providing a potential lead for broad-spectrum antiviral drug therapy.
AB - We investigated the potential of small peptide segments to function as broad-spectrum antiviral drug leads. We extracted the a-helical peptide segments that share common secondary-structure environments in the capsid protein protein interfaces of three unrelated virus classes (PRD1-like, HK97-like, and BTV-like) that encompass different levels of pathogenicity to humans, animals, and plants. The potential for the binding of these peptides to the individual capsid proteins was then investigated using blind docking simulations. Most of the extracted a-helical peptides were found to interact favorably with one or more of the protein protein interfaces within the capsid in all three classes of virus. Moreover, binding of these peptides to the interface regions was found to block one or more of the putative "hot spot" regions on the protein interface, thereby providing the potential to disrupt virus capsid assembly via competitive interaction with other capsid proteins. In particular, binding of the GDFNALSN peptide was found to block interface "hot spot" regions in most of the viruses, providing a potential lead for broad-spectrum antiviral drug therapy.
UR - http://www.scopus.com/inward/record.url?scp=84859184542&partnerID=8YFLogxK
U2 - 10.1021/ci200467s
DO - 10.1021/ci200467s
M3 - Article
SN - 1549-9596
VL - 52
SP - 770
EP - 776
JO - Journal of chemical information and modeling
JF - Journal of chemical information and modeling
IS - 3
ER -