title: Virucidal activity of a scorpion venom peptide variant mucroporin-M1 against measles, SARS-CoV and influenza H5N1 viruses.
abstract: Outbreaks of SARS-CoV, influenza A (H5N1, H1N1) and measles viruses in recent years have raised serious concerns about the measures available to control emerging and re-emerging infectious viral diseases. Effective antiviral agents are lacking that specifically target RNA viruses such as measles, SARS-CoV and influenza H5N1 viruses, and available vaccinations have demonstrated variable efficacy. Therefore, the development of novel antiviral agents is needed to close the vaccination gap and silence outbreaks. We previously identified mucroporin, a cationic host defense peptide from scorpion venom, which can effectively inhibit standard bacteria. The optimized mucroporin-M1 can inhibit gram-positive bacteria at low concentrations and antibiotic-resistant pathogens. In this investigation, we further tested mucroporin and the optimized mucroporin-M1 for their antiviral activity. Surprisingly, we found that the antiviral activities of mucroporin-M1 against measles, SARS-CoV and influenza H5N1 viruses were notably increased with an EC₅₀ of 7.15 μg/ml (3.52 μM) and a CC₅₀ of 70.46 μg/ml (34.70 μM) against measles virus, an EC₅₀ of 14.46 μg/ml (7.12 μM) against SARS-CoV and an EC₅₀ of 2.10 μg/ml (1.03 μM) against H5N1, while the original peptide mucroporin showed no antiviral activity against any of these three viruses. The inhibition model could be via a direct interaction with the virus envelope, thereby decreasing the infectivity of virus. This report provides evidence that host defense peptides from scorpion venom can be modified for antiviral activity by rational design and represents a practical approach for developing broad-spectrum antiviral agents, especially against RNA viruses.
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, People's Republic of China.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.forename: Zhenhuan
authors.initials: Z
authors.lastname: Zhao
authors.forename: Dihan
authors.initials: D
authors.lastname: Zhou
authors.forename: Yaoqing
authors.initials: Y
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Hong
authors.forename: Luyang
authors.initials: L
authors.lastname: Cao
authors.forename: Jingyi
authors.initials: J
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cao
authors.forename: Yingliang
authors.initials: Y
authors.lastname: Wu
authors.forename: Huimin
authors.initials: H
authors.lastname: Yan
authors.forename: Wenxin
authors.initials: W
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D004285:Dogs; D015195:Drug Design; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000502:physiology; D007251:Influenza, Human / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D020128:Inhibitory Concentration 50; D008457:Measles / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D008969:Molecular Sequence Data; D018103:Morbillivirus / Q000187:drug effects* / Q000502:physiology; D058873:Pandemics / Q000517:prevention & control; D011485:Protein Binding; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000502:physiology; D012604:Scorpion Venoms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012605:Scorpions / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D014759:Viral Envelope Proteins / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D012604:Scorpion Venoms; D014759:Viral Envelope Proteins