Unit:
ΠΜΣ με ειδίκευση ΣΥΝΘΕΤΙΚΗ ΦΑΡΜΑΚΕΥΤΙΚΗ ΧΗΜΕΙΑLibrary of the School of Science
Author:
Τζιτζογλάκη Χριστίνα
Supervisors info:
Αντώνιος Κολοκούρης Αναπλ. Καθηγητής ΕΚΠΑ (επιβλέπων), Παναγιώτης Μαράκος Καθηγητής ΕΚΠΑ, Ανδρέας Tσοτίνης Καθηγητής ΕΚΠΑ
Original Title:
Δραστικά αμινοαδαμαντάνια που περιορίζουν την μετάλλαξη προς ανθεκτικά στελέχη του νέου ιού Influenza A S31N
Translated title:
Αdamantanes with persistent in vitro efficacy against H1N1 (2009) Ιnfluenza Α
Summary:
A series of 2-adamantanamines with adducts of various lengths were examined for
efficacy against strains of influenza A. The addition of as little as one CH2
group to the methyl adduct of the amantadine/rimantadine analog,
2-methyl-2-aminoadamantane, led to activity in vitro against two M2 S31N
viruses, A/PR/8/34 (H1N1) and A/Calif/04/2009 (H1N1). For one compound tested
with the 2009 virus, 10 passages (~5 weeks) in the presence of drug were
required before significant resistance developed. While proteoliposome assays,
ssNMR data and MD simulations using fragments of M2 are consistent with a
direct block of the S31N M2 transmembrane domain, electrophysiology using the
whole S31N M2 protein showed no blockade. A wild type strain, A/Hong Kong/1/64
(H3N2) developed resistance to these drugs within one passage with mutations
in M2 TM, but the strain of A/Calif/04/2009 S31N that developed resistance in
vitro had no mutations in M2 TM. The results suggest that 2-adamantanamines
with sufficient adducts can persistently block p2009 influenza A in vitro.
Keywords:
Persistent, Influenza A , S31N, 2-adamantanamines , Electrophysiology
