title: Identification and synthesis of quinolizidines with anti-influenza a virus activity.
abstract: Influenza A virus infection causes a contagious respiratory illness that poses a threat to human health. However, there are limited anti-influenza A therapeutics available, which is further compounded by the emergence of drug resistant viruses. In this study, Sophora quinolizidine alkaloids were identified as a new class of anti-influenza A virus agents. Among the tested Sophora alkaloids, dihydroaloperine exhibited the most potent activity with an EC50 of 11.2 μM. The potency of the quinolizidine alkaloids was improved by approximately 5-fold with chemical modifications on the aloperine molecule. These compounds were effective against an H1N1 influenza A virus that was resistant to the two antiflu drugs oseltamivir and amantadine. The identification of the quinolizidine alkaloids as effective and novel anti-influenza A agents may aid in the development of new therapeutics.
authors.affiliation: Surgical Science, Department of Surgery, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Dang
authors.affiliation: Surgical Science, Department of Surgery, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Katherine
authors.initials: K
authors.lastname: Jung
authors.affiliation: Surgical Science, Department of Surgery, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Surgical Science, Department of Surgery, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Weihong
authors.initials: W
authors.lastname: Lai
authors.affiliation: School of Dentistry, Meharry Medical College , Nashville, Tennessee 37208, United States.
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.affiliation: Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina , Chapel Hill, North Carolina 27599, United States ; Chinese Medicine Research and Development Center, China Medical University and Hospital , Taichung, Taiwan.
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Surgical Science, Department of Surgery, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: Surgical Science, Department of Surgery, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Chin-Ho
authors.initials: CH
authors.lastname: Chen
keywords: Influenza; influenza inhibitor; nucleoprotein