The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Unveiling the Chemical Composition and Biofunctionality of <i>Hericium</i> spp. Fungi: A Comprehensive Overview

In recent years, research on mushrooms belonging to the Hericium genus has attracted considerable attention due to their unique appearance and well-known medicinal properties. These mushrooms are abundant in bioactive chemicals like polysaccharides, hericenones, erinacines, hericerins, resorcinols, steroids, mono- and diterpenes, and corallocins, alongside essential nutrients. These compounds demonstrate beneficial bioactivities which are related to various physiological systems of the body, including the digestive, immune, and nervous systems. Extensive research has been conducted on the isolation and identification of numerous bioactive chemicals, and both in vitro and in vivo studies have confirmed their antimicrobial, antioxidant, immunomodulatory, antidiabetic, anticholesterolemic, anticancer, and neuroprotective properties. Therefore, this review aims to provide a comprehensive summary of the latest scientific literature on the chemical composition and secondary metabolites profile of Hericium spp. through an introduction to their chemical characteristics, speculated biosynthesis pathways for key chemical families, potential toxicological aspects, and a detailed description of the recent updates regarding the bioactivity of these metabolites

Pharmaceuticals as Emerging Pollutants in the Reclaimed Wastewater Used in Irrigation and Their Effects on Plants, Soils, and Groundwater

Pharmaceuticals and personal care products (PPCPs) were investigated in five wastewater treatment plants (WWTPs), groundwater, irrigated soils, and plants in Amman and Al-Balqa governorates in Jordan. PPCPs were extracted from water samples by solid-phase extraction (SPE) and analyzed by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC&ndash;MS/MS). Carbamazepine, ciprofloxacin, ceftiofur, diclofenac, erythromycin, lincomycin, ofloxacin, pyrimthamine, spiramycin, sulfamethoxazole, sulfapyridine, testosterone, trimethoprim, and thiamphenicol were detected in all raw wastewaters in &mu;g/L, whereas 45 PPCPs were below the detection limits (&lt;0.02 &mu;g/L) in all samples. Na`ur and Abu Nuseir WWTPs showed high PPCPs removal efficiencies in comparison with AL-Baqa`a, Salt, and Fuhais-Mahis WWTPs. Boqorreya spring showed signs of contamination by Salt WWTP effluents as a result of mixing. Irrigation with effluents showed higher carbamazepine concentrations in soils at the top soil layers (0 to 20 cm) in all farms than its concentrations at the root zone (20 to 40 cm) by using drip irrigation system with various plants. In plants, carbamazepine concentration was only detected in high concentration level in mint leaves. In the same farm, diclofenac concentration was detected only in olives and not in twigs and leaves, indicating a high rate of plant uptake especially during the olive&rsquo;s growth period. Furthermore, plant fruits, leaves, and stems left on the farm after harvesting are generally consumed by cattle, which means entering the food chain of humans

Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study

Paraoxonase 1 (PON1) plays a role in regulating reverse cholesterol transport and has antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities. Scientists are currently focused on the modulation of PON1 expression using different pharmacological, nutritional, and lifestyle approaches. We previously isolated a novel active compound from Nannochloropsis microalgae—lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS)—which increased PON1 activity, HDL-cholesterol efflux, and endothelial nitric oxide release. Here, to explore this important lipid moiety’s effect on PON1 activities, we examined the effect of synthesized lipid derivatives and endogenous analogs of lyso-DGTS on PON1 lactonase and arylesterase activities and LDL oxidation using structure–activity relationship (SAR) methods. Six lipids significantly elevated recombinant PON1 (rePON1) lactonase activity in a dose-dependent manner, and four lipids significantly increased rePON1 arylesterase activity. Using tryptophan fluorescence-quenching assay and a molecular docking method, lipid–PON1 interactions were characterized. An inverse correlation was obtained between the lactonase activity of PON1 and the docking energy of the lipid–PON1 complex. Furthermore, five of the lipids increased the LDL oxidation lag time and inhibited its propagation. Our findings suggest a beneficial effect of lyso-DGTS or lyso-DGTS derivatives through increased PON1 activity and prevention of LDL oxidation

S-Nitrosylation of Paraxonase 1 (PON1) Elevates Its Hydrolytic and Antioxidant Activities

Covalent binding between nitric oxide (NO) and a protein’s free thiol group (SH) is termed protein S-nitrosylation. Protein S-nitrosylation is involved in cellular regulation mechanisms that underlie a wide range of critical functions, such as apoptosis, alteration of enzyme activities, and transcription-factor stability. Impaired protein S-nitrosylation is associated with a growing list of pathophysiological conditions, such as cardiovascular disease, multiple sclerosis, pulmonary hypertension, and sickle cell disease. The enzyme paraoxonase 1 (PON1) binds to high-density lipoprotein to provide many of its antiatherogenic properties. The enzyme has a strong antioxidant capacity, which protects fats, lipids, and lipoproteins from oxidation, in addition to breaking down oxidized fats. We investigated the effect of S-S transnitrosylation on PON1 activities. Incubation of recombinant PON1 (rePON1) with nitrosylated human serum albumin (HSA-NO) resulted in S-nitrosylation of about 70% of the rePON1, as measured by Q-TOF LC/MS. S-nitrosylation significantly increased rePON1 hydrolytic activities. It also increased rePON1’s ability to inhibit low-density lipoprotein oxidation induced by Cu2+. Finally, it increased the enzyme’s penetration into macrophage cells by 31%. Our findings suggest that S-nitrosylation of rePON1 improves its biological functions which may positively affect atherosclerosis disease progression

Quantitative immunocytochemical assay for infectious avian retroviruses.

A simple and accurate immunocytochemical focus assay is described, whereby both transforming and non-transforming avian retroviruses can be enumerated. After virus infection of chick embryo fibroblasts, an agar overlay is applied; foci of infected cells (expression foci) are detected immunocytochemically after 5 to 7 days. The primary antibodies are monoclonal sera directed against either viral p19gag or pp60v-src. Detection of expression foci after transfection of cells with cloned viral DNA is also demonstrated

Overcoming Chemoresistance in Cancer: The Promise of Crizotinib

: Chemoresistance is a major obstacle in cancer treatment, often leading to disease progression and poor outcomes. It arises through various mechanisms such as genetic mutations, drug efflux pumps, enhanced DNA repair, and changes in the tumor microenvironment. These processes allow cancer cells to survive despite chemotherapy, underscoring the need for new strategies to overcome resistance and improve treatment efficacy. Crizotinib, a first-generation multi-target kinase inhibitor, is approved by the FDA for the treatment of ALK-positive or ROS1-positive non-small cell lung cancer (NSCLC), refractory inflammatory (ALK)-positive myofibroblastic tumors (IMTs) and relapsed/refractory ALK-positive anaplastic large cell lymphoma (ALCL). Crizotinib exists in two enantiomeric forms: (R)-crizotinib and its mirror image, (S)-crizotinib. It is assumed that the R-isomer is responsible for the carrying out various processes reviewed here The S-isomer, on the other hand, shows a strong inhibition of MTH1, an enzyme important for DNA repair mechanisms. Studies have shown that crizotinib is an effective multi-kinase inhibitor targeting various kinases such as c-Met, native/T315I Bcr/Abl, and JAK2. Its mechanism of action involves the competitive inhibition of ATP binding and allosteric inhibition, particularly at Bcr/Abl. Crizotinib showed synergistic effects when combined with the poly ADP ribose polymerase inhibitor (PARP), especially in ovarian cancer harboring BRCA gene mutations. In addition, crizotinib targets a critical vulnerability in many p53-mutated cancers. Unlike its wild-type counterpart, the p53 mutant promotes cancer cell survival. Crizotinib can cause the degradation of the p53 mutant, sensitizing these cancer cells to DNA-damaging substances and triggering apoptosis. Interestingly, other reports demonstrated that crizotinib exhibits anti-bacterial activity, targeting Gram-positive bacteria. Also, it is active against drug-resistant strains. In summary, crizotinib exerts anti-tumor effects through several mechanisms, including the inhibition of kinases and the restoration of drug sensitivity. The potential of crizotinib in combination therapies is emphasized, particularly in cancers with a high prevalence of the p53 mutant, such as triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSOC)

Ir(III)-PC(sp³)P Bifunctional Catalysts for Production of H₂ by Dehydrogenation of Formic Acid: Experimental and Theoretical Study

Reversible storage of hydrogen in the form of stable and relatively harmless chemical substances such as formic acid (FA) is one of the cornerstones of a fossil-fuel-free economy. Recently, Ru­(III)-PC­(sp³)P (where PC­(sp³)P = modular dibenzobarrelene-based pincer ligand possessing a pendant functional group) complex <b>1</b> has been reported as a mild and <i>E</i>-selective catalyst in semihydrogenation of alkynes with stoichiometric neat formic acid. Discovery of the additive-free protocol for dehydrogenation of FA launched further studies aiming at the rational design of highly efficient catalysts for this reaction operating under neutral conditions. We now report the results of our investigation on a series of bifunctionl PC­(sp³)P complexes equipped with different outer-sphere auxiliaries, that allowed us to identify an amine-functionalized Ir­(III)-PC­(sp³)P complex <b>3</b>, as a clean and efficient catalyst for the FA dehydrogenation. The catalyst is suitable for fuel-cell applications demonstrating a TON up to 5 × 10⁵ and TOF up to 2 × 10⁴ h^–1 (3.8 × 10⁵ and 1.2 × 10⁴ h^–1 with no additives). In addition to the practical value of the catalyst, experimental and computational mechanistic studies provide rationale for the design of improved next-generation catalysts

Conformational Flexibility of Dibenzobarrelene-Based PC(sp³)P Pincer Iridium Hydride Complexes: The Role of Hemilabile Functional Groups and External Coordinating Solvents

Bifunctional dibenzobarrelene-based PC­(sp³)P pincer iridium complex <b>1</b> is known as an efficient catalyst in acceptorless dehydrogenation of alcohols and hydrogenation/hydroformylation of alkenes. In order to shed light on the mechanism of the hydrogen formation/activation, we performed variable-temperature IR and NMR (¹H, ³¹P) analysis of intra- and intermolecular interactions involving a hydride ligand and hydroxymethyl cooperating group in <b>1</b> and its analogues. The results of the spectroscopic measurements in different media (dichloromethane, toluene, DMSO, and mixed solvents) were compared with the quantum chemical (DFT/M06 and B3PW91) calculations. The obtained data imply flexibility of the dibenzobarrelene-based scaffold, unprecedented for conventional pincer ligands. Both the CH₂OH-substituted complex <b>1</b> and its COOEt analogue <b>3</b> prefer facial configuration of the PCP ligand with a P–Ir–P angle of ca. 100°. Such geometries are stabilized by Ir···O interaction with the dangling functional group and differ by the mutual arrangement of the H and Cl ligands. The complexes show dynamic equilibrium between the two most stable <i>fac</i>-isomers, which can be transformed into the meridional ones in the presence of coordinating additives (CH₃CN, DMSO, or CO, but not Et₃N). The process is reversible for CH₃CN but irreversible for DMSO and CO, in agreement with the Lewis basicity of these molecules