Identification of Kukoamine A, Zeaxanthin, and Clexane as New Furin Inhibitors.

The endogenous protease furin is a key protein in many different diseases, such as cancer and infections. For this reason, a wide range of studies has focused on targeting furin from a therapeutic point of view. Our main objective consisted of identifying new compounds that could enlarge the furin inhibitor arsenal; secondarily, we assayed their adjuvant effect in combination with a known furin inhibitor, CMK, which avoids the SARS-CoV-2 S protein cleavage by means of that inhibition. Virtual screening was carried out to identify potential furin inhibitors. The inhibition of physiological and purified recombinant furin by screening selected compounds, Clexane, and these drugs in combination with CMK was assayed in fluorogenic tests by using a specific furin substrate. The effects of the selected inhibitors from virtual screening on cell viability (293T HEK cell line) were assayed by means of flow cytometry. Through virtual screening, Zeaxanthin and Kukoamine A were selected as the main potential furin inhibitors. In fluorogenic assays, these two compounds and Clexane inhibited both physiological and recombinant furin in a dose-dependent way. In addition, these compounds increased physiological furin inhibition by CMK, showing an adjuvant effect. In conclusion, we identified Kukoamine A, Zeaxanthin, and Clexane as new furin inhibitors. In addition, these drugs were able to increase furin inhibition by CMK, so they could also increase its efficiency when avoiding S protein proteolysis, which is essential for SARS-CoV-2 cell infection.

Enfermedad de Devic. Reporte de caso y revisión de literatura / Devic's disease. A case report and literature review

Resumen La neuromielitis óptica (NMO) o enfermedad de Devic, es una enfermedad inflamatoria infrecuente del sistema nervioso central (SNC) que afecta predominantemente el nervio óptico y la médula espinal. El mecanismo de la enfermedad es dado por la producción de anticuerpos IgG cuyo principal blanco inmunitario es el canal acuaporina 4 (AQP4), los cuales desencadenan un proceso inflamatorio y desmielinizante en dichas estructuras. Presentamos el caso de una paciente, quien desarrolló episodios sensitivos crónicos fluctuantes con afección visual, sin mejoría con el tratamiento convencional; durante el abordaje diagnóstico se encontraron lesiones desmielinizantes y anticuerpos anti-AQP4 positivos, por lo que se concluyó el diagnóstico de NMO, y respondió de manera positiva al tratamiento con anticuerpos monoclonales.

Abstract Optic neuromyelitis or Devic's disease is a rare inflammatory disease of the central nervous system (CNS) that predominantly affects the optic nerve and spinal cord. The mechanism of the disease is given by the production of IgG antibodies whose main target is the acuaporine channel 4 (AQP4) that trigger an inflammatory and demyelinating process in the aforementioned structures. We present the case of a patient who developed chronic and fluctuating sensitive episodes with visual impairment, without improvement after conventional treatment. During the diagnostic approach we found demyelinating lesions and positive AQP4-antibodies, this lead to a diagnosis of optic neuromyelitis. A positive response was obtained to the therapy with monoclonal antibodies.