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Since the information about the evolution of these viruses in Saudi is deficient so we investigated the genetic diversity of circulating H1N1 viruses. Nasopharyngeal aspirates\/swabs collected from 149 patients hospitalized with flu\u2010like symptoms during 2014 and 2015 were analyzed. Viral RNA extraction was followed by a reverse transcription\u2010polymerase chain reaction and genetic sequencing. We analyzed complete gene sequences of HA and NA from 80 positive isolates. Phylogenetic analysis of HA and NA genes of 80 isolates showed similar topologies and co\u2010circulation of clades 6b. Genetic diversity was observed among circulating viruses belonging to clade 6B.1A. The amino acid residues in the HA epitope domain were under purifying selection. Amino acid changes at key antigenic sites, such as position S101N, S179N (antigenic site\u2010Sa), I233T (antigenic site\u2010Sb) in the head domain might have resulted in antigenic drift and emergence of variant viruses. For NA protein, 36% isolates showed the presence of amino acid changes such as V13I (n\u2009=\u200929), I314M (n\u2009=\u200929) and 12% had I34V (n\u2009=\u200910). However, H257Y mutation responsible for resistance to neuraminidase inhibitors was missing. The presence of amino acid changes at key antigenic sites and their topologies with structural mapping of residues under purifying selection highlights the importance of antigenic drift and warrants further characterization of recently circulating viruses in view of vaccine effectiveness. The co\u2010circulation of several clades and the predominance of clade 6B.1 suggest multiple introductions in Saudi.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmv.25759","type":"journal-article","created":{"date-parts":[[2020,3,11]],"date-time":"2020-03-11T10:10:02Z","timestamp":1583921402000},"page":"3016-3027","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Antigenic drift of hemagglutinin and neuraminidase in seasonal H1N1 influenza viruses from Saudi Arabia in 2014 to 2015"],"prefix":"10.1002","volume":"92","author":[{"given":"Asif","family":"Naeem","sequence":"first","affiliation":[{"name":"Research Center King Fahad Medical City  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Elbakkouri","sequence":"additional","affiliation":[{"name":"Research Center King Fahad Medical City  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Alfaiz","sequence":"additional","affiliation":[{"name":"Research Center King Fahad Medical City  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaweya E.","family":"Hamed","sequence":"additional","affiliation":[{"name":"College of Science King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadel","family":"Alsaran","sequence":"additional","affiliation":[{"name":"Research Center King Fahad Medical City  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahad","family":"AlOtaiby","sequence":"additional","affiliation":[{"name":"Research Center King Fahad Medical City  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mushira","family":"Enani","sequence":"additional","affiliation":[{"name":"Medical Specialties Department, Section of Infectious Diseases King Fahad Medical City  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4719-2655","authenticated-orcid":false,"given":"Bandar","family":"Alosaimi","sequence":"additional","affiliation":[{"name":"Research Center King Fahad Medical City  Riyadh Saudi Arabia"},{"name":"College of Medicine King Fahad Medical City  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"World Health Organization. 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