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Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/MuteSwan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing.
Background. The bay cat Catopuma badia is endemic to Borneo, whereas its sister species the Asian golden cat Catopuma temminckii is distributed from the Himalayas and southern China through Indochina, Peninsular Malaysia and Sumatra. Based onmorphological data, up to five subspecies of the Asian golden cat have been recognized, but a taxonomic assessment, including molecular data and morphological characters, is still lacking. Results. We combined molecular data (whole mitochondrial genomes), morphological data (pelage) and species distribution projections (up to the Late Pleistocene) to infer how environmental changes may have influenced the distribution of these sister species over the past 120 000 years. The molecular analysis was based on sequenced mitogenomes of 3 bay cats and 40 Asian golden cats derived mainly from archival samples. Our molecular data suggested a time of split between the two species approximately 3.16 Ma and revealed very low nucleotide diversity within the Asian golden cat population, which supports recent expansion of the population. Discussion. The low nucleotide diversity suggested a population bottleneck in the Asian golden cat, possibly caused by the eruption of the Toba volcano in Northern Sumatra (approx. 74 kya), followed by a continuous population expansion in the Late Pleistocene/Early Holocene. Species distribution projections, the reconstruction of the demographic history, a genetic isolation-by-distance pattern and a gradual variation of pelage pattern support the hypothesis of a post-Toba population expansion of the Asian golden cat from south China/Indochina to PeninsularMalaysia and Sumatra. Our findings reject the current classification of five subspecies for the Asian golden cat, but instead support either a monotypic species or one comprising two subspecies: (i) the Sunda golden cat, distributed south of the Isthmus of Kra: C. t. temminckii and (ii) Indochinese, Indian, Himalayan and Chinese golden cats, occurring north of the Isthmus: C. t. moormensis.