Lipoarabinomannan modification as a source of phenotypic heterogeneity in host-adapted Mycobacterium abscessus isolates.

Mycobacterium abscessus is increasingly recognized as the causative agent of chronic pulmonary infections in humans. One of the genes found to be under strong evolutionary pressure during adaptation of M. abscessus to the human lung is embC which encodes an arabinosyltransferase required for the biosynthesis of the cell envelope lipoglycan, lipoarabinomannan (LAM). To assess the impact of patient-derived embC mutations on the physiology and virulence of M. abscessus, mutations were introduced in the isogenic background of M. abscessus ATCC 19977 and the resulting strains probed for phenotypic changes in a variety of in vitro and host cell-based assays relevant to infection. We show that patient-derived mutational variations in EmbC result in an unexpectedly large number of changes in the physiology of M. abscessus, and its interactions with innate immune cells. Not only did the mutants produce previously unknown forms of LAM with a truncated arabinan domain and 3-linked oligomannoside chains, they also displayed significantly altered cording, sliding motility, and biofilm-forming capacities. The mutants further differed from wild-type M. abscessus in their ability to replicate and induce inflammatory responses in human monocyte-derived macrophages and epithelial cells. The fact that different embC mutations were associated with distinct physiologic and pathogenic outcomes indicates that structural alterations in LAM caused by nonsynonymous nucleotide polymorphisms in embC may be a rapid, one-step, way for M. abscessus to generate broad-spectrum diversity beneficial to survival within the heterogeneous and constantly evolving environment of the infected human airway.

Old drugs for a new indication: a review of chloroquine and analogue in COVID-19 treatment.

As an innovative therapeutic strategy, drug repurposing affords old, approved, and already established drugs a chance at new indications. In the wake of the COVID-19 pandemic and the accompanied urgency for a lasting treatment, drug repurposing has come in handy to stem the debilitating effects of the disease. Among other therapeutic options currently in clinical trials, chloroquine (CQ) and the hydroxylated analogue, hydroxychloroquine (HCQ) have been frontline therapeutic options in most formal and informal clinical settings with varying degrees of efficacy against this life-threatening disease. Their status in randomized clinical trials is related to the biochemical and pharmacological profiles as validated by in vitro, in vivo and case studies. With the aim to bear a balance for their use in the long run, this review not only synopsizes findings from recent studies on the degrees of efficacy and roles of CQ/HCQ as potential anti-COVID-19 agents but also highlights our perspectives for their consideration in rational drug repositioning and use.

Recent SARS-CoV-2 Outlook and Implications in a COVID-19 Vaccination Era.

While repurposed drugs came in handy earlier in the wake of the coronavirus disease 2019 (COVID-19) pandemic, vaccination has been considered a more sustainable approach. The recent spikes have been linked to "double," "triple," and even multi-mutant variants, thus renewing calls for deeper structural and functional insights of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a lead to rationale design of therapeutics, vaccines, and point-of-care diagnostics. There is a repertoire of findings from the earliest SARS-CoV-2 molecular mimicry to evade host immunity cum host immune responses to the role of the viral glycocalyx in modulating the susceptibility and severity of infection through attraction and repulsive interactions. Recently, molecular studies of some viral components that aid infection in the face of vaccination seem unending. In addition, the wave of infections and the attendant case fatality ratios have necessitated the need for emergency use authorizations for COVID-19 vaccines and in vitro diagnostics. This review provides key updates of SARS-CoV-2, current antigenic and formulation strategies, with emergency use authorizations considerations for future vaccine candidates and diagnostics. We also premise that despite the difficulty in modeling and analyzing glycans, understanding and exploiting their roles in the SARS-CoV-2 architecture is fundamental to glycan-based COVID-19 vaccines devoid of inconsistent clinical outcomes.

Bio- and chemical syntheses of mangiferin and congeners.

Mangiferin (2C-ß-d-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone) is a xanthone C-glycoside occurring in many plant species. Composed of a glucose unit C1→2 linked to a 1,3,6,7-tetrahydroxyxanthone aglycone, mangiferin exhibits a wide range of biological activities, which recently renewed its interest as a potential pharmacophore. Mangiferin is mainly isolated after extraction procedures from natural sources alongside with its isoforms isomangiferin, homomangiferin, and neomangiferin. However, enzymatic and chemical approaches have been developed to access these phytochemicals, which address the challenging construction of the C-glycosidic linkage. In addition, both approaches have been exploited to modify the aglycone and the sugar moiety in order to afford analogues with specific and improved pharmacological activities. Herein, we provide a comprehensive review on the biosynthesis and chemical synthesis of mangiferin and its congeners. © 2016 BioFactors, 42(5):445-458, 2016.

HPLC analysis of nicotinamide, pyridoxine,riboflavin and thiamin in some selected food products in Nigeria

Food fortification is an important tool for improving the health of the population. Motivated by this; the National Agency for Food and Drug Administration and Control (NAFDAC) has in the past few years embarked on a campaign to create this awareness. There has been varying degree of compliance to this; and so it is of utmost importance to know the food products that contribute significantly to the dietary vitamin B intake. This study investigates the amount of four Vitamin B compounds; namely nicotinamide; pyridoxine; riboflavin and thiamin; present in different packaged food items available in Lagos metropolis of Nigeria. The food items analyzed include dairy products; fruit juices and cereal products. These foods were chosen because of their widespread consumption in the area. The analysis was done using a high performance liquid chromatographic technique with a UV detector. The separation was carried out on a C18 column; using a mobile phase made up of 70buffer (a solution of sodium salt of hexane sulphonic acid) and 30HPLC grade methanol. The identification was based on retention time match against a standard while the quantitation was based on the peak area match against those of a standard. The calibration curves for the standards were linear with a linear regression coefficient close to unity