germacrone and Orthomyxoviridae-Infections

Influenza virus is one of the most widespread infectious diseases in the world. It poses a serious public health threat to humans. With the emergence of drug-resistant virus strains, antiviral drugs are urgently needed to control virus transmission and disease progression. In this study, three main active substances-curcumol, curdione and germacrone-were isolated from the traditional Chinese medicine zedoary. They inhibited the replication of influenza A (H1N1) virus in a dose-dependent manner. After treatment with these compounds, the expression of viral protein and RNA synthesis were inhibited. In vivo, these compounds also reduced H1N1-induced lung damage and the load of virus in serum as well as whole blood cells. In a proteomic analysis, after treatment with germacrone, the expression of antiviral protein and the amount of intracellular virus were significantly reduced, further proving that germacrone can inhibit viral replication. Our experiments have shown that curcumol, curdione and germacrone can inhibit the replication of H1N1 virus; in particular, germacrone shows potential both in vitro and in vivo as a therapeutic drug.

Topics: A549 Cells; Animals; Antiviral Agents; Cell Proliferation; Drugs, Chinese Herbal; HEK293 Cells; Humans; Influenza A Virus, H1N1 Subtype; Mice; Mice, Inbred BALB C; Molecular Structure; Oils; Orthomyxoviridae Infections; Sesquiterpenes; Sesquiterpenes, Germacrane; Specific Pathogen-Free Organisms

Highly pathogenic influenza viruses pose a serious public health threat to humans. Although vaccines are available, antivirals are needed to efficiently control disease progression and virus transmission due to the emergence of drug-resistant viral strains. In this study, germacrone, which is a major component of the essential oils extracted from Rhizoma Curcuma, was found to inhibit influenza virus replication. Germacrone showed antiviral activity against the H1N1 and H3N2 influenza A viruses and the influenza B virus in a dose-dependent manner. The viral protein expression, RNA synthesis and the production of infectious progeny viruses were decreased both in MDCK and A549 cells treated with germacrone. In a time-of-addition study, germacrone was found to exhibit an inhibitory effect on both the attachment/entry step and the early stages of the viral replication cycle. Germacrone also exhibited an effective protection of mice from lethal infection and reduced the virus titres in the lung. Furthermore, the combination of germacrone and oseltamivir exhibited an additive effect on the inhibition of influenza virus infection, both in vitro and in vivo. Our results suggest that germacrone may have the potential to be developed as a therapeutic agent alone or in combination with other agents for the treatment of influenza virus infection.

Topics: Animals; Antiviral Agents; Cell Line; Chick Embryo; Dogs; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Therapy, Combination; Drugs, Chinese Herbal; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza B virus; Lung; Madin Darby Canine Kidney Cells; Mice; Orthomyxoviridae Infections; Oseltamivir; Phytotherapy; Ribavirin; Sesquiterpenes, Germacrane; Specific Pathogen-Free Organisms; Virus Attachment; Virus Cultivation; Virus Replication