COVID-19 & Pregnancy Complication During Early Pandemic: A Narrative Review

Background: Coronaviruses have caused 3 outbreaks in the past 2 decades. The novel one is SARS-COV-2, which causes COVID-19. Pregnant women have somewhat altered immune state, which may make them more vulnerable to COVID-19 and its complications. Extensive research is needed to better understand the clinical course of COVID-19 in this population. Objective: This review article discusses the comparison of previous coronaviruses’ outbreaks, clinical presentations, and complications in pregnant women and newborns. Study Design: We conducted literature search for case series and case reports about pregnancy outcomes in pregnant women with COVID-19 during the early phase of pandemic. Results: In case series, 37 of 129(28.6%) pregnant women with COVID-19 disease had preterm delivery and 14 of 67 pregnant women had fetal distress. The rate of preterm labor in normal pregnant women who are healthy and not infected with any virus worldwide is approximately 11%. Conclusion: Based on the articles reviewed, preterm delivery appears to be the most common complication in COVID-19 pregnant patients. Other complications include fetal distress, stillbirth, ICU admission and severe disease leading to fetal demise and maternal mortality. Pregnancy outcomes seem to be better with Covid-19 compared to SARs and MERS. However, most of these publications are from the early part of the pandemic when protocols for care for pregnant women were being worked out and comprehensive knowledge of the disease process in pregnant women was still in developing stage

Comparative Pharmacokinetic Study of Two Lyophilized Orally Disintegrating Tablets Formulations of Vinpocetine in Human Volunteers

Vinpocetine is a poorly water soluble drug, commonly used in treatment of various cerebral insufficiency conditions. The aim of this work was to formulate vinpocetine in the form of orally disintegrating tablets (ODTs) and enhance its solubility and dissolution rate. This objective was addressed using lyophilization technique of either solid dispersion using polyethylene glycol 4000 (PEG 4000) or inclusion complex with 2-hydroxypropyl β-cyclodextrin (2HP-β-CD). Differential scanning calorimetry (DSC) and fourier transform-infrared (FT-IR) spectroscopy were used to characterize the solid state of the prepared solid complex. Tablets were prepared by direct compression using 23 factorial design to evaluate the effect of formulation variables (Ac-di-sol concentration 5 or 10%, the ratio of soluble polymer 1:1 or 1:3 and binder type 6% w/w Avicel PH102 or 6% w/w carboxymethyl cellulose) on release characteristics. Results showed that lyophilized ODTs disintegrated within few seconds and had significantly faster dissolution rate (70-100 % in 5 minutes) compared to the commercial oral tablet (Cavinton®). This was achieved at high content of PEG 4000 or 2 HP-β-CD in presence of 10 % w/w Ac-Di-Sol and 6 % w/w Avicel PH102. The extent of per oral absorption of vinpocetine was determined in healthy human volunteers using randomized crossover design. The relative bioavailability of selected solid dispersion and inclusion complex formulations were found to be 171.98 % and 196.06 % respectively. The study indicated that complexation of vinpocetine with 2-HP-βCD or dispersion in PEG 4000 followed by lyophilization are two successful strategies for enhancing the bioavailability of the drug from ODTs

A Motif Unique to the Human Dead-Box Protein DDX3 Is Important for Nucleic Acid Binding, ATP Hydrolysis, RNA/DNA Unwinding and HIV-1 Replication

DEAD-box proteins are enzymes endowed with nucleic acid-dependent ATPase, RNA translocase and unwinding activities. The human DEAD-box protein DDX3 has been shown to play important roles in tumor proliferation and viral infections. In particular, DDX3 has been identified as an essential cofactor for HIV-1 replication. Here we characterized a set of DDX3 mutants biochemically with respect to nucleic acid binding, ATPase and helicase activity. In particular, we addressed the functional role of a unique insertion between motifs I and Ia of DDX3 and provide evidence for its implication in nucleic acid binding and HIV-1 replication. We show that human DDX3 lacking this domain binds HIV-1 RNA with lower affinity. Furthermore, a specific peptide ligand for this insertion selected by phage display interferes with HIV-1 replication after transduction into HelaP4 cells. Besides broadening our understanding of the structure-function relationships of this important protein, our results identify a specific domain of DDX3 which may be suited as target for antiviral drugs designed to inhibit cellular cofactors for HIV-1 replication

Signatures of Selection in Fusion Transcripts Resulting From Chromosomal Translocations in Human Cancer

BACKGROUND: The recurrence and non-random distribution of translocation breakpoints in human tumors are usually attributed to local sequence features present in the vicinity of the breakpoints. However, it has also been suggested that functional constraints might contribute to delimit the position of translocation breakpoints within the genes involved, but a quantitative analysis of such contribution has been lacking. METHODOLOGY: We have analyzed two well-known signatures of functional selection, such as reading-frame compatibility and non-random combinations of protein domains, on an extensive dataset of fusion proteins resulting from chromosomal translocations in cancer. CONCLUSIONS: Our data provide strong experimental support for the concept that the position of translocation breakpoints in the genome of cancer cells is determined, to a large extent, by the need to combine certain protein domains and to keep an intact reading frame in fusion transcripts. Additionally, the information that we have assembled affords a global view of the oncogenic mechanisms and domain architectures that are used by fusion proteins. This can be used to assess the functional impact of novel chromosomal translocations and to predict the position of breakpoints in the genes involved

Comparative Structural Analysis of Human DEAD-Box RNA Helicases

DEAD-box RNA helicases play various, often critical, roles in all processes where RNAs are involved. Members of this family of proteins are linked to human disease, including cancer and viral infections. DEAD-box proteins contain two conserved domains that both contribute to RNA and ATP binding. Despite recent advances the molecular details of how these enzymes convert chemical energy into RNA remodeling is unknown. We present crystal structures of the isolated DEAD-domains of human DDX2A/eIF4A1, DDX2B/eIF4A2, DDX5, DDX10/DBP4, DDX18/myc-regulated DEAD-box protein, DDX20, DDX47, DDX52/ROK1, and DDX53/CAGE, and of the helicase domains of DDX25 and DDX41. Together with prior knowledge this enables a family-wide comparative structural analysis. We propose a general mechanism for opening of the RNA binding site. This analysis also provides insights into the diversity of DExD/H- proteins, with implications for understanding the functions of individual family members

Vasa-Like DEAD-Box RNA Helicases of Schistosoma mansoni

Genome sequences are available for the human blood flukes, Schistosoma japonicum, S. mansoni and S. haematobium. Functional genomic approaches could aid in identifying the role and importance of these newly described schistosome genes. Transgenesis is established for functional genomics in model species, which can lead to gain- or loss-of-functions, facilitate vector-based RNA interference, and represents an effective forward genetics tool for insertional mutagenesis screens. Progress toward routine transgenesis in schistosomes might be expedited if germ cells could be reliably localized in cultured schistosomes. Vasa, a member of the ATP-dependent DEAD-box RNA helicase family, is a prototypic marker of primordial germ cells and the germ line in the Metazoa. Using bioinformatics, 33 putative DEAD-box RNA helicases exhibiting conserved motifs that characterize helicases of this family were identified in the S. mansoni genome. Moreover, three of the helicases exhibited vasa-like sequences; phylogenetic analysis confirmed the three vasa-like genes—termed Smvlg1, Smvlg2, and Smvlg3—were members of the Vasa/PL10 DEAD-box subfamily. Transcripts encoding Smvlg1, Smvlg2, and Smvlg3 were cloned from cDNAs from mixed sex adult worms, and quantitative real time PCR revealed their presence in developmental stages of S. mansoni with elevated expression in sporocysts, adult females, eggs, and miracidia, with strikingly high expression in the undeveloped egg. Whole mount in situ hybridization (WISH) analysis revealed that Smvlg1, Smvlg2 and Smvlg3 were transcribed in the posterior ovary where the oocytes mature. Germ cell specific expression of schistosome vasa-like genes should provide an informative landmark for germ line transgenesis of schistosomes, etiologic agents of major neglected tropical diseases

The human DDX and DHX gene families of putative RNA helicases.

Nucleic acid helicases are characterized by the presence of the helicase domain containing eight motifs. The sequence of the helicase domain is used to classify helicases into families. To identify members of the DEAD and DEAH families of human RNA helicases, we used the helicase domain sequences to search the nonredundant peptide sequence database. We report the identification of 36 and 14 members of the DEAD and DEAH families of putative RNA helicases, including several novel genes. The gene symbol DDX had been used previously for both DEAD- and DEAH-box families. We have now adopted DDX and DHX symbols to denote DEAD- and DEAH-box families, respectively. Members of human DDX and DHX families of putative RNA helicases play roles in differentiation and carcinogenesis