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

LC-ToF-ESI-MS Patterns of Hirsutinolide-like Sesquiterpenoids Present in the Elephantopus mollis Kunth Extract and Chemophenetic Significance of Its Chemical Constituents

Bitchagno Mbahbou GT, Koffi JG, Simo IK, et al. LC-ToF-ESI-MS Patterns of Hirsutinolide-like Sesquiterpenoids Present in the Elephantopus mollis Kunth Extract and Chemophenetic Significance of Its Chemical Constituents. Molecules. 2021;26(16): 4810.A total of nine sesquiterpenoid lactones together with phenolic compounds and other terpenes were identified from the crude methanol extract of Elephantopus mollis Kunth. Compounds were isolated using different chromatographic techniques and their structures were determined by NMR and IR spectroscopy as well as mass spectrometry. The structures of some detected compounds were assigned based on LC-ToF-ESI-MS screening of main fractions/subfractions from flash chromatography and comparison with isolated analogues as standards. The findings revealed not only the in-source loss of water as the base peak in hirsutinolides but also the in-source loss of corresponding alcohol when the oxygen at position 1 is alkylated. The present study also draws up a complement of data with respect to hirsutinolide-like sesquiterpene lactones whose LC-MS characteristics are not available in the literature. The chemophenetic significance is also discussed. Some of the isolated compounds were reported for the first time to be found in the species, the genus as well as the plant family. The medium-polar fractions of the crude extract, also containing the larger amount of sesquiterpenoid lactones, exhibited activity both against a cancer cell line and bacterial strains. Isolated lactones were also active against the cancer cell line, while the chlorogenic derivatives also valuable in Elephantopus genus showed potent radical scavenging activity. This is the first report of cytotoxic and antibacterial activities of our samples against the tested strains and cell line. The present study follows the ongoing research project dealing with the characterization of taxa with antibacterial and antiparasitic activities from Cameroonian pharmacopeia

Antileishmanial, antibacterial and cytotoxicity activity of the extracts, fractions, and compounds from the fruits and stem bark extracts of Sabine

Garba JK, Nguengang RT, Youmbi GT, et al. Antileishmanial, antibacterial and cytotoxicity activity of the extracts, fractions, and compounds from the fruits and stem bark extracts of Sabine. Zeitschrift für Naturforschung B. 2022;77(1):9-15.**Abstract** The search for antileishmanial plants used in traditional medicine led to the choice of CH2Cl2–MeOH (1:1) crude extract of the fruits and stem bark ofPentadesma butyraceaSabine (Clusiaceae) which displayed good activityin vitroagainstLeishmania donovani1S (MHOM/SD/62/1S) promastigotes during preliminary screening with IC50values 5.96 and 26.43 μg mL−1, respectively. The fractionation of both extracts using flash chromatography yielded active fractions with IC50values ranging from 2.71 to 18.88 μg mL−1. Fourteen compounds (1–14) were isolated from the obtained fractions using successive column chromatographies and their structures were elucidated based on the analysis of their NMR and MS data. Daphnifolin (1), epicathechin (3), α-mangostin (9) and 9-hydroxycalabaxanthone (14) exhibited potent antileismanial activity againstL. donovani1S (MHOM/SD/62/1S) promastigotes with IC50values of 2.01, 9.09, 3.37, and 6.87 μg mL−1, respectively and good selectivity towards Raw 264.7 macrophage cells (SI > 2.4). Extracts, fractions and some isolates were also assessed in vitro for their antibacterial activity against six bacterial strains [Salmonella typhi(CPC),Enterobacter cloacae(CPC),Pseudomonas aeruginosaHM801,Staphylococcus aureusATCC 43300,Streptococcus pneumoniaeATCC 491619,Escherichia coliATCC 25322] using serial microdilution method. Among the tested samples, the stem bark extract ofP. butyraceaas well as compounds2and8showed good to moderate activity against the aforementioned bacterial strains with MIC ≤ 250 μg mL−1

Identification of 3,3'-O-dimethylellagic acid and apigenin as the main antiplasmodial constituents of Endodesmia calophylloides Benth and Hymenostegia afzelii (Oliver.) Harms

Keumoe R, Koffi JG, Dize D, et al. Identification of 3,3'-O-dimethylellagic acid and apigenin as the main antiplasmodial constituents of Endodesmia calophylloides Benth and Hymenostegia afzelii (Oliver.) Harms. BMC complementary medicine and therapies. 2021;21(1): 180.BACKGROUND: Endodesmia calophylloides and Hymenostegia afzelii belong to the Guttiferae and Caesalpiniaceae plant families with known uses in African ethno-medicine to treat malaria and several other diseases. This study aimed at identifying antiplasmodial natural products from selected crude extracts from H. afzelii and E. calophylloides and to assess their cytotoxicity.; METHODS: The extracts from H. afzelii and E. calophylloides were subjected to bioassay-guided fractionation to identify antiplasmodial compounds. The hydroethanol and methanol stem bark crude extracts, fractions and isolated compounds were assessed for antiplasmodial activity against the chloroquine-sensitive 3D7 and multi-drug resistant Dd2 strains of Plasmodium falciparum using the SYBR green I fluorescence-based microdilution assay. Cytotoxicity of active extracts, fractions and compounds was determined on African green monkey normal kidney Vero and murine macrophage Raw 264.7 cell lines using the Resazurin-based viability assay.; RESULTS: The hydroethanolic extract of H. afzelii stem bark (HasbHE) and the methanolic extract of E. calophylloides stem bark (EcsbM) exhibited the highest potency against both Pf3D7 (EC50 values of 3.32±0.15mug/mL and 7.40±0.19mug/mL, respectively) and PfDd2 (EC50 of 3.08±0.21mug/mL and 7.48±0.07mug/mL, respectively) strains. Both extracts showed high selectivity toward Plasmodium parasites (SI>13). The biological activity-guided fractionation led to the identification of five compounds (Compounds 1-5) from HasbHE and one compound (Compound 6) from EcsbM. Of these, Compound 1 corresponding to apigenin (EC50 Pf3D7, of 19.01±0.72muM and EC50 PfDd2 of 16.39±0.52muM), and Compound 6 corresponding to 3,3'-O-dimethylellagic acid (EC50 Pf3D7 of 4.27±0.05muM and EC50 PfDd2 of 1.36±0.47muM) displayed the highest antiplasmodial activities. Interestingly, both compounds exhibited negligible cytotoxicity against both Vero and Raw 264.7 cell lines with selectivity indices greater than 9.; CONCLUSIONS: This study led to the identification of two potent antiplasmodial natural compounds, 3,3'-O-dimethylellagic acid and apigenin that could serve as starting points for further antimalarial drug discovery