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      Evaluation of Baloxavir Marboxil and Peramivir for the Treatment of High Pathogenicity Avian Influenza in Chickens

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          Abstract

          Control measures in the case of high pathogenicity avian influenza (HPAI) outbreaks in poultry include culling, surveillance, and biosecurity; wild birds in captivity may also be culled, although some rare bird species should be rescued for conservation. In this study, two anti-influenza drugs, baloxavir marboxil (BXM) and peramivir (PR), used in humans, were examined in treating HPAI in birds, using chickens as a model. Chickens were infected with H5N6 HPAI virus and were treated immediately or 24 h from challenge with 20 mg/kg BXM or PR twice a day for five days. As per our findings, BXM significantly reduced virus replication in organs and provided full protection to chickens compared with that induced by PR. In the 24-h-delayed treatment, neither drug completely inhibited virus replication nor ensured the survival of infected chickens. A single administration of 2.5 mg/kg of BXM was determined as the minimum dose required to fully protect chickens from HPAI virus; the concentration of baloxavir acid, the active form of BXM, in chicken blood at this dose was sufficient for a 48 h antiviral effect post-administration. Thus, these data can be a starting point for the use of BXM and PR in treating captive wild birds infected with HPAI virus.

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          Most cited references37

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          A SIMPLE METHOD OF ESTIMATING FIFTY PER CENT ENDPOINTS12

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            Evolution and ecology of influenza A viruses.

            In this review we examine the hypothesis that aquatic birds are the primordial source of all influenza viruses in other species and study the ecological features that permit the perpetuation of influenza viruses in aquatic avian species. Phylogenetic analysis of the nucleotide sequence of influenza A virus RNA segments coding for the spike proteins (HA, NA, and M2) and the internal proteins (PB2, PB1, PA, NP, M, and NS) from a wide range of hosts, geographical regions, and influenza A virus subtypes support the following conclusions. (i) Two partly overlapping reservoirs of influenza A viruses exist in migrating waterfowl and shorebirds throughout the world. These species harbor influenza viruses of all the known HA and NA subtypes. (ii) Influenza viruses have evolved into a number of host-specific lineages that are exemplified by the NP gene and include equine Prague/56, recent equine strains, classical swine and human strains, H13 gull strains, and all other avian strains. Other genes show similar patterns, but with extensive evidence of genetic reassortment. Geographical as well as host-specific lineages are evident. (iii) All of the influenza A viruses of mammalian sources originated from the avian gene pool, and it is possible that influenza B viruses also arose from the same source. (iv) The different virus lineages are predominantly host specific, but there are periodic exchanges of influenza virus genes or whole viruses between species, giving rise to pandemics of disease in humans, lower animals, and birds. (v) The influenza viruses currently circulating in humans and pigs in North America originated by transmission of all genes from the avian reservoir prior to the 1918 Spanish influenza pandemic; some of the genes have subsequently been replaced by others from the influenza gene pool in birds. (vi) The influenza virus gene pool in aquatic birds of the world is probably perpetuated by low-level transmission within that species throughout the year. (vii) There is evidence that most new human pandemic strains and variants have originated in southern China. (viii) There is speculation that pigs may serve as the intermediate host in genetic exchange between influenza viruses in avian and humans, but experimental evidence is lacking. (ix) Once the ecological properties of influenza viruses are understood, it may be possible to interdict the introduction of new influenza viruses into humans.
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              Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents

              Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                08 December 2020
                December 2020
                : 12
                : 12
                : 1407
                Affiliations
                [1 ]Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan; ttaugushahu@ 123456vetmed.hokudai.ac.jp (A.T.); okamatsu@ 123456vetmed.hokudai.ac.jp (M.O.); nisoda@ 123456vetmed.hokudai.ac.jp (N.I.)
                [2 ]Virology Service, Central Veterinary Laboratory of Kinshasa, Ministry of Fisheries and Livestock, Kinshasa I/Gombe 012, Democratic Republic of the Congo
                [3 ]International Collaboration Unit, Research Center for Zoonosis Control, Hokkaido University, Sapporo 011-0020, Japan; matsuk@ 123456czc.hokudai.ac.jp
                [4 ]Unit of Risk Analysis and Management, Research Center for Zoonotic Control, Hokkaido University, Sapporo 011-0020, Japan
                Author notes
                [* ]Correspondence: sakoda@ 123456vetmed.hokudai.ac.jp ; Tel.: +81-1-1706-5207; Fax: +81-1-1706-5273
                Author information
                https://orcid.org/0000-0003-0695-2734
                https://orcid.org/0000-0002-4205-6526
                https://orcid.org/0000-0001-7021-1688
                Article
                viruses-12-01407
                10.3390/v12121407
                7762593
                33302389
                2b808b82-7b78-43f2-94fa-17bcf5abe274
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 11 November 2020
                : 07 December 2020
                Categories
                Article

                Microbiology & Virology
                baloxavir marboxil,peramivir,treatment,high pathogenicity avian influenza,chicken model

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