Amantadine Variant – Aryl Conjugates that Inhibit Multiple M2 Mutant – Amantadine Resistant Influenza A Viruses
نویسندگان
چکیده
منابع مشابه
Oseltamivir- and Amantadine-Resistant Influenza Viruses A (H1N1)
Surveillance of amantadine and oseltamivir resistance among influenza viruses was begun in Hong Kong in 2006. In 2008, while both A/Brisbane/59/2007-like and A/Hong Kong/2652/2006-like viruses (H1N1) were cocirculating, we detected amantadine and oseltamivir resistance among A/Hong Kong/2652/2006-like viruses (H1N1), caused by genetic reassortment or spontaneous mutation.
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Background and Aims: Influenza A viruses are important pathogens for humans especially in pandemic episodes. Two adamantane derivates, amantadine and rimantadine, are used for prophylaxis and treatment of influenza A virus infections. However, single amino acid substitutions in the M2 transmembrane domain which lead to amantadine resistance of these viruses occur at residues 26, 27, 30, 31 or 3...
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Using the newly designed mismatch amplification mutation assay (MAMA) PCR, we demonstrated the high frequency of amantadine-resistant influenza A (H3N2) viruses isolated during the 2005-2006 season by detecting the mutation at amino acid position 31 of the M2 protein (S31N). Further, phylogenetic analyses of the HA1 sequences of the S31N viruses revealed that they comprised a clonal lineage tha...
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The limited efficacy of existing antiviral therapies for influenza--coupled with widespread baseline antiviral resistance--highlights the urgent need for more effective therapy. We describe a triple combination antiviral drug (TCAD) regimen composed of amantadine, oseltamivir, and ribavirin that is highly efficacious at reducing mortality and weight loss in mouse models of influenza infection. ...
متن کاملWhy Bound Amantadine Fails to Inhibit Proton Conductance According to Simulations of the Drug-Resistant Influenza A M2 (S31N)
The mechanisms responsible for drug resistance in the Asn31 variant of the M2 protein of influenza A are not well understood. Molecular dynamics simulations were performed on wild-type (Ser31) and S31N influenza A M2 in the homotetramer configuration. After evaluation of 13 published M2 structures, a solid-state NMR structure with amantadine bound was selected for simulations, an S31N mutant st...
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ژورنال
عنوان ژورنال: Social Science Research Network
سال: 2022
ISSN: ['1556-5068']
DOI: https://doi.org/10.2139/ssrn.4163276