NS2B-NS3 protease inhibitors as promising compounds in the development of antivirals against Zika virus: A systematic review.

Zika virus (ZIKV) infections are associated with severe neurological complications and are a global public health concern. There are no approved vaccines or antiviral drugs to inhibit ZIKV replication. NS2B-NS3 protease (NS2B-NS3 pro), which is essential for viral replication, is a promising molecular target for anti-ZIKV drugs. We conducted a systematic review to identify compounds with promising effects against ZIKV; we discussed their pharmacodynamic and pharmacophoric characteristics. The online search, performed using the PubMed/MEDLINE and SCOPUS databases, yielded 56 articles; seven relevant studies that reported nine promising compounds with inhibitory activity against ZIKV NS2B-NS3 pro were selected. Of these, five (niclosamide, nitazoxanide, bromocriptine, temoporfin, and novobiocin) are currently available on the market and have been tested for off-label use against ZIKV. The 50% inhibitory concentration values of these compounds for the inhibition of NS2B-NS3 pro ranged at 0.38-21.6 µM; most compounds exhibited noncompetitive inhibition (66%). All compounds that could inhibit the NS2B-NS3 pro complex showed potent in vitro anti-ZIKV activity with a 50% effective concentration ranging 0.024-50 µM. The 50% cytotoxic concentration of the compounds assayed using A549, Vero, and WRL-69 cell lines ranged at 0.6-1388.02 µM and the selectivity index was 3.07-1698. This review summarizes the most promising antiviral agents against ZIKV that have inhibitory activity against viral proteases.

Epidemiological Impact and Hospitalization costs applied to dengue in the Midwest region of Minas Gerais state, Brazil, from SUS perspective.

BACKGROUND & OBJECTIVES: Dengue is considered one of the greatest public health challenges in the world, especially, for tropical and subtropical countries. Brazil highlights with considerable number of registers associated with this arbovirus, with emphasis on the state of Minas Gerais and its municipalities in regions such as the midwest. We aimed to evaluate the economic and epidemiological impact of dengue in the midwest region of minas Gerais, from SUS perspective. METHODS: Our study evaluated the epidemiological impact of dengue fever in the midwest region of Minas Gerais using data applied to Divinópolis city from SUS perspective between 2000 to 2015 considering SIH/SUS database (hospitalization registers) and 2007 to 2017 using the SINAN database (notification cases). We analyzed the number of notification registers and hospital services, as well as their costs, from a SUS perspective associated with this infection. RESULTS: There were 26,516 notifications associated with dengue, with 21,953 cases being confirmed by SEMUSA, with a median incidence of 211 cases/100,000 inhabitants of dengue notifications between 2007 and 2017. The southeast and southwest regions in the municipality are highlighted with high number of cases. Additionally, 160 hospitalizations were recorded with 33.79% in individuals between 15 and 34 years old and expenses of USD 53,737.21 for SUS between 2000 and 2015. INTERPRETATION & CONCLUSION: Divinópolis is the reference (social and economic) municipality of the midwest region in Minas Gerais state. Our study is the first conducted involving a long period of follow up applied to dengue context in this locality, especially, including the costs associated with hospitalization services. We hope to contribute to the discussions regarding the coping strategies of the disease, considering the impact in its different regions, highlighting the need for continued efforts and initiatives aimed at combating the vector of this and other arboviruses such as Zika and chikungunya.

Antifungal activity of a shortened analogue of the natural peptide LyeTx I isolated from the venom of the spider Lycosa erythrognatha.

The increase in the incidence of fungal infections associated with the limited therapeutic arsenal available and the increasing rate of resistance of pathogenic fungi reinforce the need for research of new antifungal agents. Thus, this study aims to evaluate the antifungal activity of the peptide LyeTx I mnΔK, a shortened analogue of the natural peptide LyeTx I derived from spider venom, against Candida species. LyeTx I mnΔK showed potent activity against Candida spp. with minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) between 4 and 32 µM. The peptide also completely inhibited the yeast-to-hypha transition (at 2 µM) and broke mature biofilms (67% reduction at 32 µM) of C. albicans. In addition, LyeTx I mnΔK did not induce resistance in C. albicans during 21 days of exposure. Therefore, the LyeTx I mnΔK is a promising prototype for the development of new antifungal agents.