Chalcones from Angelica keiskei (ashitaba) inhibit key Zika virus replication proteins.

Zika virus (ZIKV) is a dangerous human pathogen and no antiviral drugs have been approved to date. The chalcones are a group of small molecules that are found in a number of different plants, including Angelica keiskei Koidzumi, also known as ashitaba. To examine chalcone anti-ZIKV activity, three chalcones, 4-hydroxyderricin (4HD), xanthoangelol (XA), and xanthoangelol-E (XA-E), were purified from a methanol-ethyl acetate extract from A. keiskei. Molecular and ensemble docking predicted that these chalcones would establish multiple interactions with residues in the catalytic and allosteric sites of ZIKV NS2B-NS3 protease, and in the allosteric site of the NS5 RNA-dependent RNA-polymerase (RdRp). Machine learning models also predicted 4HD, XA and XA-E as potential anti-ZIKV inhibitors. Enzymatic and kinetic assays confirmed chalcone inhibition of the ZIKV NS2B-NS3 protease allosteric site with IC50s from 18 to 50 µM. Activity assays also revealed that XA, but not 4HD or XA-E, inhibited the allosteric site of the RdRp, with an IC50 of 6.9 µM. Finally, we tested these chalcones for their anti-viral activity in vitro with Vero cells. 4HD and XA-E displayed anti-ZIKV activity with EC50 values of 6.6 and 22.0 µM, respectively, while XA displayed relatively weak anti-ZIKV activity with whole cells. With their simple structures and relative ease of modification, the chalcones represent attractive candidates for hit-to-lead optimization in the search of new anti-ZIKV therapeutics.

[Zoonotic tuberculosis in Argentina]. / La tuberculosis zoonótica en la Argentina.

There are significant achievements in the control of animal tuberculosis (tB) in Argentina. the percentage of bovines with apparent tB lesions at the slaughterhouse inspection decreased from 6.7% to 0.6% between 1969 and 2011. on the other hand, the mean percentage of human tB cases due to M. bovis among all those bacteriologically confirmed, was in Santa Fe, an agro-industrial province, 2.3% in the period 1977-2001. It fell to 1.6% by 2011. In the Cetrángolo Hospital (Buenos Aires), it was 0.34% in the period 2001-2005, and 0.36% in 2006-2011. At the Muñiz Hospital, these percentages decreased from 1.75% in 1971 to 0.22% in 2006. Frequency of HIV infection among M. bovis cases varied from 5.9% in santa Fe to 11.1% and 20.5% respectively, in Cetrángolo and Muñiz Hospitals (a reference institution for aids) in Buenos Aires. According to these data M. bovis infection predominates in agro-industrial/ rural areas, showing a slow decrease there as well as in Buenos Aires. Co-infection with HIV is more frequent among patients with M. bovis that in all cases of tB. The situation of M. bovis in Argentina is here compared with that in USA and in several European and Latin American countries. Trends followed by tB in cattle, in humans, and the percentages of M. bovis among them, are not always closely related to move towards the common goal of eradicating tB; the employment of appropriate strategies and the strengthening of control measures are critical in both programs.

La tuberculosis zoonótica en la Argentina / Zoonotic tuberculosis in Argentina

Existen importantes logros en el control de la tuberculosis (TB) animal en la Argentina. Los porcentajes de bovinos con lesiones TB halladas en mataderos disminuyeron de 6.7% a 0.7% entre 1969 y 2011. En salud pública, el porcentaje promedio de TB por M. bovis sobre el total de los casos confirmados bacteriológicamente, fue en Santa Fe -provincia agro industrial- 2.3% en el período 1977-2001 y 1.6% entre 2002 y 2011. En Buenos Aires, en el Hospital Cetrángolo, ese porcentaje fue 0.34% (2001-2005) y 0.36% (2006-2011). En el Hospital Muñiz disminuyó de 1.75% en 1971 a 0.22% en 2006. La frecuencia de HIV entre los casos de M. bovis varió de 5.9% en Santa Fe a 11.1% y 20.5% respectivamente en los Hospitales Cetrángolo y Muñiz de Buenos Aires. En conjunto, la infección por M. bovis es más importante en las zonas rurales/ agro industriales, con un lento descenso, también observado en Buenos Aires. La coinfección por HIV es más frecuente en pacientes con M. bovis que en el conjunto de los casos de TB. Comparando la situación de la Argentina con la de EE.UU. y países de Europa y América Latina, se observa que las tendencias de la TB en el ganado, en humanos y la frecuencia relativa del M. bovis en salud pública, no siempre siguen una relación estrecha. Para avanzar hacia la meta común de erradicación de la TB, el empleo de estrategias adecuadas y el fortalecimiento de las medidas de control son fundamentales para ambos programas.

There are significant achievements in the control of animal tuberculosis (TB) in Argentina. The percentage of bovines with apparent TB lesions at the slaughterhouse inspection decreased from 6.7% to 0.6% between 1969 and 2011. On the other hand, the mean percentage of human TB cases due to M. bovis among all those bacteriologically confirmed, was in Santa Fe, an agro-industrial province, 2.3% in the period 1977-2001. It fell to 1.6% by 2011. In the Cetrángolo Hospital (Buenos Aires), it was 0.34% in the period 2001-2005, and 0.36% in 2006-2011. At the Muñiz Hospital, these percentages decreased from 1.75% in 1971 to 0.22% in 2006. Frequency of HIV infection among M. bovis cases varied from 5.9% in Santa Fe to 11.1% and 20.5% respectively, in Cetrángolo and Muñiz Hospitals (a reference institution for aids) in Buenos Aires. According to these data M. bovis infection predominates in agro- industrial/ rural areas, showing a slow decrease there as well as in Buenos Aires. Co-infection with HIV is more frequent among patients with M. bovis that in all cases of TB. The situation of M. bovis in Argentina is here compared with that in USA and in several European and Latin American countries. Trends followed by TB in cattle, in humans, and the percentages of M. bovis among them, are not always closely related. To move towards the common goal of eradicating TB, the employment of appropriate strategies and the strengthening of control measures are critical in both programs.

La tuberculosis zoonótica en la Argentina / Zoonotic tuberculosis in Argentina

Existen importantes logros en el control de la tuberculosis (TB) animal en la Argentina. Los porcentajes de bovinos con lesiones TB halladas en mataderos disminuyeron de 6.7% a 0.7% entre 1969 y 2011. En salud pública, el porcentaje promedio de TB por M. bovis sobre el total de los casos confirmados bacteriológicamente, fue en Santa Fe -provincia agro industrial- 2.3% en el período 1977-2001 y 1.6% entre 2002 y 2011. En Buenos Aires, en el Hospital Cetrángolo, ese porcentaje fue 0.34% (2001-2005) y 0.36% (2006-2011). En el Hospital Muñiz disminuyó de 1.75% en 1971 a 0.22% en 2006. La frecuencia de HIV entre los casos de M. bovis varió de 5.9% en Santa Fe a 11.1% y 20.5% respectivamente en los Hospitales Cetrángolo y Muñiz de Buenos Aires. En conjunto, la infección por M. bovis es más importante en las zonas rurales/ agro industriales, con un lento descenso, también observado en Buenos Aires. La coinfección por HIV es más frecuente en pacientes con M. bovis que en el conjunto de los casos de TB. Comparando la situación de la Argentina con la de EE.UU. y países de Europa y América Latina, se observa que las tendencias de la TB en el ganado, en humanos y la frecuencia relativa del M. bovis en salud pública, no siempre siguen una relación estrecha. Para avanzar hacia la meta común de erradicación de la TB, el empleo de estrategias adecuadas y el fortalecimiento de las medidas de control son fundamentales para ambos programas.(AU)

There are significant achievements in the control of animal tuberculosis (TB) in Argentina. The percentage of bovines with apparent TB lesions at the slaughterhouse inspection decreased from 6.7% to 0.6% between 1969 and 2011. On the other hand, the mean percentage of human TB cases due to M. bovis among all those bacteriologically confirmed, was in Santa Fe, an agro-industrial province, 2.3% in the period 1977-2001. It fell to 1.6% by 2011. In the Cetrángolo Hospital (Buenos Aires), it was 0.34% in the period 2001-2005, and 0.36% in 2006-2011. At the Muñiz Hospital, these percentages decreased from 1.75% in 1971 to 0.22% in 2006. Frequency of HIV infection among M. bovis cases varied from 5.9% in Santa Fe to 11.1% and 20.5% respectively, in Cetrángolo and Muñiz Hospitals (a reference institution for aids) in Buenos Aires. According to these data M. bovis infection predominates in agro- industrial/ rural areas, showing a slow decrease there as well as in Buenos Aires. Co-infection with HIV is more frequent among patients with M. bovis that in all cases of TB. The situation of M. bovis in Argentina is here compared with that in USA and in several European and Latin American countries. Trends followed by TB in cattle, in humans, and the percentages of M. bovis among them, are not always closely related. To move towards the common goal of eradicating TB, the employment of appropriate strategies and the strengthening of control measures are critical in both programs.(AU)