Structure-based discovery of thiosemicarbazones as SARS-CoV-2 main protease inhibitors.

Aim: Discovery of novel SARS-CoV-2 main protease (Mpro) inhibitors using a structure-based drug discovery strategy. Materials & methods: Virtual screening employing covalent and noncovalent docking was performed to discover Mpro inhibitors, which were subsequently evaluated in biochemical and cellular assays. Results: 91 virtual hits were selected for biochemical assays, and four were confirmed as reversible inhibitors of SARS CoV-2 Mpro with IC50 values of 0.4-3 µM. They were also shown to inhibit SARS-CoV-1 Mpro and human cathepsin L. Molecular dynamics simulations indicated the stability of the Mpro inhibitor complexes and the interaction of ligands at the subsites. Conclusion: This approach led to the discovery of novel thiosemicarbazones as potent SARS-CoV-2 Mpro inhibitors.

Tablet-based tele-audiometry: Automated hearing screening for schoolchildren.

Introduction: To assess the performance of a tablet-based tele-audiometry method for automated hearing screening of schoolchildren through a comparison of the results of various hearing screening approaches. Methods: A total of 244 children were evaluated. Tablet-based screening results were compared with gold-standard pure-tone audiometry. Acoustic immittance measurements were also conducted. To pass the tablet-based screening, the children were required to respond to at least two out of three sounds for all the frequencies in each ear. Several hearing screening methods were analysed: exclusively tablet-based (with and without 500 Hz checked) and combined tests (series and parallel). The sensitivity, specificity, positive and negative predictive values and accuracy were calculated. Results: A total of 9.43% of children presented with mild to moderate conductive hearing loss (unilateral or bilateral). Diagnostic values varied among the different hearing screening approaches that were evaluated: sensitivities ranged from 60 to 95%, specificities ranged from 44 to 91%, positive predictive values ranged from 15 to 44%, negative predictive values ranged from 95 to 99%, accuracy values ranged from 49 to 88%, and area under curve values ranged from 0.690 to 0.883. Regarding diagnostic values, the highest results were found for the tablet-based screening method and for the series approach. Discussion: Compared with the results obtained by conventional audiometry and considering the diagnostic values of the different hearing screening approaches, the highest diagnostic values were generally obtained using the automated hearing screening method (including 500 Hz). Thus, this application, which was developed for the tablet computer, was shown to be a valuable hearing screening tool for use with schoolchildren. Therefore, we suggest that this hearing screening protocol has the potential to improve asynchronous tele-audiology service delivery.

Prevalência de marcadores sorológicos e moleculares do vírus da hepatite B em gestantes do Estado do Amazonas, Brasil / Prevalence of serologic and molecular markers of hepatitis B virus infectio among pregnant women in Amazonas State, Brazil

A infecção pelo vírus da hepatite B (VHB) constitui um importante problema de Saúde Pública na Amazônia brasileira, onde a exposição precoce, durante a infância, ocorre em áreas de maior endemicidade. Com a finalidade de contribuir para as políticas regionais de controle do VHB na região, foi conduzido um inquérito de prevalência de marcadores sorológicos e moleculares do VHB entre 1.460 gestantes atendidas pelo Programa Pré-Natal, nas nove sub-regiões do Estado do Amazonas, Brasil. Entre essas subregiões, a prevalência do antígeno de superfície (HBsAg) variou de 0 por cento a 8,7 por cento; dos anticorpos anti-core (anti-HBc), de 5,3 a 75,9 por cento;e de anticorpos anti-superfície (anti-HBs), de 10,6 a 73,4 por cento. Entre as 46 gestantes reativas para o HBsAg, 36 (78,3 por cento) foram positivas para VHB-DNA na reação em cadeia da polimerase (PCR). A carga viral de VHB-DNA foi menor que 1x103 cópias/ml em 73,9 por cento das gestantes HBsAg-reativas; porém, 8,7 por cento apresentavam níveis superiores a 1x105 cópias/ml, indicando infecção ativa. Os resultados encontrados mostram sub-regiões do Amazonas com elevada prevalência de VHB entre mulheres grávidas e, embora a maioria apresente baixa viremia, algumas podem representar risco potencial de transmissão mãe-filho, devido à elevada carga viral