<p></p><p><b>Entrance of coronavirus into cells happens through the spike proteins on the virus surface, for which the spike protein should be cleaved into S1 and S2 domains. This cleavage is mediated by furin, which can specifically cleav</b><b>e</b><b> Arg-X-X-Arg↓ sites of the substrates. Furin, a member of proprotein convertases family, is moved from the trans-Golgi network to the cell membrane and activates many precursor proteins. A number of pathological conditions such as atherosclerosis, cancer, and viral infectious diseases, are linked with the impaired activity of this enzyme. </b></p> <p><b>Despite the urgent need to control COVID-19, no approved treatment is currently known. Here, folic acid (folate), a water-soluble B vitamin, is introduced for the first time for the inhibition of furin activity. As such, folic acid, as a safe drug, may help to prevent or alleviate the respiratory involvement associated with COVID-19. </b></p><br><p></p>

<p></p><p><b>Entrance of coronavirus into cells happens through the spike proteins on the virus surface, for which the spike protein should be cleaved into S1 and S2 domains. This cleavage is mediated by furin, which can specifically cleav</b><b>e</b><b> Arg-X-X-Arg↓ sites of the substrates. Furin, a member of proprotein convertases family, is moved from the trans-Golgi network to the cell membrane and activates many precursor proteins. A number of pathological conditions such as atherosclerosis, cancer, and viral infectious diseases, are linked with the impaired activity of this enzyme. </b></p> <p><b>Despite the urgent need to control COVID-19, no approved treatment is currently known. Here, folic acid (folate), a water-soluble B vitamin, is introduced for the first time for the inhibition of furin activity. As such, folic acid, as a safe drug, may help to prevent or alleviate the respiratory involvement associated with COVID-19. </b></p><br><p></p>

Purpose Multidrug resistance (MDR) and the subsequent disease relapse are the major causes of childhood acute lymphoblastic leukemia (ALL) related death. The Hedgehog (Hh) signaling pathway can contribute to cancer MDR. In the current study, Smoothened ( Smo ) was selected as the experimental target due to its importance in the Hh pathway in order to evaluate its probable role in pediatric B-ALL drug resistance. Patients and methods The study included 27 pediatric B-ALL and 16 control bone marrow samples. Quantitative RT-PCR was used to investigate the expression levels of Smo and miR-326 as the key players of the Hh pathway. Western blot analysis was performed. The presence of minimal residual disease was studied using PCR-SSCP. The association between Smo expression and drug resistance was analyzed statistically. Results Results showed a significant increase in the Smo expression levels in drug-resistant patients in comparison with drug-sensitive children with B-ALL ( P =0.0128, AUC=0.82). A considerable negative association between miR-326 and Smo expression levels was identified ( r =−0.624, P =0.002). A binomial test confirmed the regulatory role of miR-326 on the translational repression of Smo ( P =0.031). Statistics showed no association between Smo and ABCA2 expression levels. However, a significant positive correlation was observed between the Smo and ABCA3 transcripts in the resistant ALL children ( r =0.607, P =0.016). Conclusion Data revealed the possible oncogenic impact of Smo on leukemogenesis and drug resistance in pediatric B-ALL. Upregulation of Smo was introduced, for the first time, as a prognostic factor for drug resistance in childhood B-ALL. To the best of our knowledge, this is the first study that shows a positive correlation between Smo and ABCA3 expression levels in pediatric B-ALL, explaining a possible mechanism for the development of drug resistance in this cancer. Moreover, the current project revealed a negative modulatory effect of miR-326 on the expression levels of Smo .

The present study introduces the ability of folic acid to interact and inhibit furin proprotein.