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Paradigm Shift Intervention Monitoring
RBD Changes In
2011 H5N1 Fatal Cluster In Bali Indonesia
The sequences had a series of receptor binding domain changes flanking position 190 (D187N, A188G, R193M). This series is remarkable similar to changes associated with the fixing of oseltamivir resistance in seasonal H1N1 (all HA sequences changed position 193 (A193T) with a variety of combinations at positions 187, 189, and 196).
R193M was also present (see list here) in the 2011 West Java sequence (A/Indonesia/NIHRD11073/2011) recently released, as well as the prior human 2008 sequence from Indonesia (A/Indonesia/7261/2008, A/Indonesia/7272/2008, A/Indonesia/8228/2008), and escape mutant from the second confirmed human case (37M) in Indonesia, A/Indonesia/05/2005, which was also a cluster.
The finding of an R193M escape mutant, as well as the presence of this receptor binding domain change in recent human cases, including the Bali cluster raises pandemic concerns.