Broad Antiviral Activity of Ginkgolic Acid against Chikungunya, Mayaro, Una, and Zika Viruses.

The alphaviruses Chikungunya (CHIKV), Mayaro (MAYV), Una (UNAV), and the flavivirus Zika (ZIKV) are emerging or re-emerging arboviruses which are responsible for frequent epidemic outbreaks. Despite the large impact of these arboviruses on health systems, there are no approved vaccines or treatments to fight these infections. As a consequence, there is an urgent need to discover new antiviral drugs. Natural products are a rich source of compounds with distinct biological activities, including antiviral properties. Thus, we aimed to explore the potential antiviral activity of Ginkgolic acid against the arboviruses CHIKV, MAYV, UNAV, and ZIKV. Viral progeny production in supernatants from cells treated or not treated with Ginkgolic acid was quantified by plaque-forming assay. Ginkgolic acid's direct virucidal activity against these arboviruses was also determined. Additionally, viral protein expression was assessed using Western blot and immunofluorescence. Our results reveal that Ginkgolic acid promotes a dose-dependent decrease in viral titers in all tested viruses. Moreover, the compound demonstrated strong virucidal activity. Finally, we found that viral protein expression was affected by treatment with this drug. Collectively, these findings suggest that Ginkgolic acid could have broader antiviral activity.

[Extensively drug-resistant tuberculosis (XDR-TB): successful therapies used in the clinic to the disease]. / Tuberculosis extensamente resistente a antibióticos (TB-XDR): terapias utilizadas con éxito en la clínica para curar la enfermedad.

Mycobacterial species have practically evolved along humankind, sometimes provoking serious diseases. Among them, tuberculosis (TB), produced by M. tuberculosiscomplex bacteria, is historically the single most devastating infectious agent. Like many other microorganisms, M. tuberculosis resistant to antibiotics have risen as a consequence of selective pressure for mutants able to persist despite being attacked with drugs that would otherwise erradicate them from the infected person. Given the current long-term (6-9 months) therapy with multiple antibiotics, many people abandon their treatments, therefore promoting that bacteria that were not eliminated during therapy get exposed to suboptimal antibiotic concentrations, probably leading to mutations and drug resistance. In this scenario, extremely-drug resistant (XDR) TB was recognized not more than a decade ago, prompting concerns for a more complicated drug regimen with few available molecules. In recent years, either old antibiotics have been rediscovered as good measures to control XDR-TB, or new ones have emerged as alternatives to cure patients of this type of infection. In this work we aim to provide the medical community in Mexico with information of such drug regimens that have succesfully worked, in order to get their consideration for use in our country.

The synthetic cathelicidin HHC-10 inhibits Mycobacterium bovis BCG in vitro and in C57BL/6 mice.

Tuberculosis causes close to 1.5 million deaths in the world, with new cases exceeding 9 million in recent years. Coinfection with HIV further worsens the global situation. New molecules that overcome the limitations of currently used drugs are needed. We aimed to determine whether HHC-10 is active against the Mycobacterium tuberculosis complex bacteria Mycobacterium bovis bacille calmette guerin (BCG) in vitro and in vivo. For this, HHC-10 was tested in vitro using different peptide concentrations, and in vivo, in C57BL/6 mice infected intratracheally, at two doses (1.25 and 2.5 mg kg(-1), once a week, 4 weeks). Interferon (IFN)-γ, TNF-α, interleukin (IL)-4, and IL-10 mRNA transcript levels were compared between treated and nontreated mice. In vitro, HHC-10 decreased 69% and 88% the number of colony-forming units (CFU) per millileter recovered after 24-hr treatment at 50 and 100 µg/ml, respectively. In vivo, BCG CFUs in mouse lungs were reduced 77.8% and 95.8% at 1.25 and 2.5 mg kg(-1), respectively. IFN-γ expression was lower in the HHC-10-treated group than that of nontreated animals. Considering genomic conservation between BCG and M. tuberculosis, the in vitro and in vivo activities of HHC-10 observed in this study suggest that the use of this peptide may be useful as therapeutic agent against tuberculosis.