A Computational Approach to Design Potential siRNA Molecules as a Prospective Tool for Silencing Nucleocapsid Phosphoprotein and Surface Glycoprotein Gene of SARS-CoV-2

A disease outbreak named COVID-19, caused by a RNA virus, SARS-CoV-2 has become 18 pandemic with a magnitude which is daunting to all public health institutions in the absence of 19 specific antiviral treatment. Surface glycoprotein and nucleocapsid phosphoprotein are two 20 important proteins of this virus facilitating its entry into host cell and genome replication. Small 21 interfering RNA (siRNA) is a prospective tool of the RNA interference (RNAi) pathway for the 22 control of human viral infections by suppressing viral gene expression through hybridization and 23 neutralization of target complementary mRNA. So, in this study, the power of RNA interference 24 technology was harnessed to develop siRNA molecules against specific target genes namely, 25 nucleocapsid phosphoprotein gene and surface glycoprotein gene. Conserved sequence from 139 26 SARS-CoV-2 strains from around the globe was collected to construct 78 siRNA that can inactivate 27 nucleocapsid phosphoprotein and surface glycoprotein genes. Finally, through a rigorous filtering 28 process 8 siRNA molecules were selected with exerts the best action. These predicted siRNAs 29 should effectively silence the genes of SARS-CoV-2 during siRNA mediated treatment assisting in 30 the response against SARS-CoV-

Perinatal colonization with extended-spectrum beta-lactamase-producing and carbapenem-resistant Gram-negative bacteria: a hospital-based cohort study

Abstract Background Antimicrobial resistance (AMR) is a growing global health threat that contributes to substantial neonatal mortality. Bangladesh has reported some of the highest rates of AMR among bacteria causing neonatal sepsis. As AMR colonization among newborns can predispose to infection with these bacteria, we aimed to characterize the frequency of and risk factors for colonization of mothers and newborns during hospitalization for delivery. Methods We enrolled pregnant women presenting for delivery to a tertiary care hospital in Faridpur, Bangladesh. We collected vaginal and rectal swabs from mothers pre- and post-delivery, rectal swabs from newborns, and swabs from the hospital environment. Swabs were plated on agars selective for extended-spectrum-beta-lactamase producing bacteria (ESBL-PB) and carbapenem-resistant bacteria (CRB). We performed logistic regression to determine factors associated with ESBL-PB/CRB colonization. Results We enrolled 177 women and their newborns during February-October 2020. Prior to delivery, 77% of mothers were colonized with ESBL-PB and 15% with CRB. 79% of women underwent cesarean deliveries (C-section). 98% of women received antibiotics. Following delivery, 98% of mothers and 89% of newborns were colonized with ESBL-PB and 89% of mothers and 72% of newborns with CRB. Of 290 environmental samples, 77% were positive for ESBL-PB and 69% for CRB. Maternal pre-delivery colonization was associated with hospitalization during pregnancy (RR for ESBL-PB 1.24, 95% CI 1.10–1.40; CRB 2.46, 95% CI 1.39–4.37). Maternal post-delivery and newborn colonization were associated with C-section (RR for maternal CRB 1.31, 95% CI 1.08–1.59; newborn ESBL-PB 1.34, 95% CI 1.09–1.64; newborn CRB 1.73, 95% CI 1.20–2.47). Conclusions In this study, we observed high rates of colonization with ESBL-PB/CRB among mothers and newborns, with pre-delivery colonization linked to prior healthcare exposure. Our results demonstrate this trend may be driven by intense use of antibiotics, frequent C-sections, and a contaminated hospital environment. These findings highlight that greater attention should be given to the use of perinatal antibiotics, improved surgical stewardship for C-sections, and infection prevention practices in healthcare settings to reduce the high prevalence of colonization with AMR organisms