Elham Moasser1, Alireza Moasser2, Hassan Zaraket3. 1. Department of Bacteriology and Virology, Shiraz University of Medical Sciences, Shiraz, Iran. 2. School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. 3. Department of Experimental Pathology, Immunology & Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon; Center for Infectious Diseases Research, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. Electronic address: hz34@aub.edu.lb.
Abstract
BACKGROUND: Two classes of antiviral drugs are available for influenza antiviral therapy: the adamantanes and the neuraminidase inhibitors (NAIs). Due to the emergence of adamantane-resistant variants, the use of these drugs has been largely limited in the world. The NAIs became the drugs of choice for treatment of influenza A infections. However, amino acid substitutions in the NA protein might lead to reduced sensitivity to NAIs. METHODS: The frequency and distribution of matrix protein 2 (M2) and neuraminidase (NA) variants which confer resistance to antiviral drugs was investigated in the Eastern Mediterranean Region (EMR) between 2005 and 2016. A total of 314 M2 and 1209 NA protein sequences from influenza A/H1N1, A/H1N1pdm09, A/H3N2, and A/H5N1 available in the public database were analyzed. RESULTS: Eighty-six percent of the influenza A viruses detected in the EMR were resistant to adamantanes, among which, H3 strains exhibited the highest (95.32%) level of adamantane resistance. Approximately 98.51% (265/269) of influenza A/H1N1 and H3N2 resistant viruses had the S31N substitution in their M2 sequences. The V27A mutation was the only resistance marker found in A/H5N1 viruses and was detected at a frequency of 7.40% among the investigated viruses. Other resistant mutations L26F, A30T, G34E, and L38F were not detected in any of the variants. We found that 2.81% (n = 34) of the detected NA sequences from influenza A viruses possessed at least one NAI-resistant mutation and the vast majority of resistant viruses 79.41% (27/34) bear the H274Y mutation. The frequency of NAI-resistant viruses was 3.29% (24/729) for the H1N1pdm09, 10.64% (5/47) for the seasonal H1N1, and 4.06% (5/123) for H5N1 viruses. None of the H3N2 viruses analyzed during the study period were resistant to NAIs. CONCLUSION: Our study reveals the emergence and spread of antiviral drug resistant influenza A viruses in the EMR and emphasizes the importance of continuous surveillance to maintain the effective use of the current antivirals.
BACKGROUND: Two classes of antiviral drugs are available for influenza antiviral therapy: the adamantanes and the neuraminidase inhibitors (NAIs). Due to the emergence of adamantane-resistant variants, the use of these drugs has been largely limited in the world. The NAIs became the drugs of choice for treatment of influenza A infections. However, amino acid substitutions in the NA protein might lead to reduced sensitivity to NAIs. METHODS: The frequency and distribution of matrix protein 2 (M2) and neuraminidase (NA) variants which confer resistance to antiviral drugs was investigated in the Eastern Mediterranean Region (EMR) between 2005 and 2016. A total of 314 M2 and 1209 NA protein sequences from influenza A/H1N1, A/H1N1pdm09, A/H3N2, and A/H5N1 available in the public database were analyzed. RESULTS: Eighty-six percent of the influenza A viruses detected in the EMR were resistant to adamantanes, among which, H3 strains exhibited the highest (95.32%) level of adamantane resistance. Approximately 98.51% (265/269) of influenza A/H1N1 and H3N2 resistant viruses had the S31N substitution in their M2 sequences. The V27A mutation was the only resistance marker found in A/H5N1 viruses and was detected at a frequency of 7.40% among the investigated viruses. Other resistant mutations L26F, A30T, G34E, and L38F were not detected in any of the variants. We found that 2.81% (n = 34) of the detected NA sequences from influenza A viruses possessed at least one NAI-resistant mutation and the vast majority of resistant viruses 79.41% (27/34) bear the H274Y mutation. The frequency of NAI-resistant viruses was 3.29% (24/729) for the H1N1pdm09, 10.64% (5/47) for the seasonal H1N1, and 4.06% (5/123) for H5N1 viruses. None of the H3N2 viruses analyzed during the study period were resistant to NAIs. CONCLUSION: Our study reveals the emergence and spread of antiviral drug resistant influenza A viruses in the EMR and emphasizes the importance of continuous surveillance to maintain the effective use of the current antivirals.
Authors: Jessica L Thomaston; Athina Konstantinidi; Lijun Liu; George Lambrinidis; Jingquan Tan; Martin Caffrey; Jun Wang; William F Degrado; Antonios Kolocouris Journal: Biochemistry Date: 2020-01-13 Impact factor: 3.162
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