Aphids are regarded as important pest problems of vegetable crops worldwide. Most vegetable growers in sub-Saharan Africa heavily rely on synthetic chemical insecticides for aphids’ control. Fungus-based biopesticides are being considered as alternatives to chemical insecticides. This study evaluates virulence of five isolates of Metarhizium anisopliae and three of Beauveria bassiana against Brevicoryne brassicae, Lipaphis pseudobrassicae, and Aphis gossypii, and their thermotolerance and conidial yield as a prerequisite for strain selection. The study also evaluates performance of the best isolate in screenhouse experiment against target aphid species. Three isolates of M. anisopliae ICIPE30, ICIPE62, and ICIPE69 outperformed the others, causing mortality of 85–98 %, 83–97 %, and 73–77 %, in B. brassicae, L. pseudobrassicae, and A. gossypii, respectively, 7 days post-inoculation. Isolate ICIPE62 had the shortest LT50 values of 3.4, 2.5, and 2.6 days at 1 × 108 conidia ml−1, and the lowest LC50 values of 7.3 × 105, 9.3 × 104, and 3.0 × 104 conidia ml−1 on day 7 against A. gossypii, B. brassicae, and L. pseudobrassicae, respectively. Furthermore, ICIPE62 produced more conidia on the surface of aphid cadavers than ICIPE30 and ICIPE69 and showed wider thermotolerance with optimum ranges between 25 and 30 °C. Application of conidia of ICIPE62 formulated in aqueous and emulsifiable formulations negatively affected aphid population growth rate on kale and okra plants compared to controls in screenhouse experiments. These results have demonstrated the potential of M. anisopliae isolate ICIPE62 in suppression of A. gossypii, B. brassicae, and L. pseudobrassicae populations and could therefore be considered as biopesticide candidate for the control of these target aphids.

The horticulture industry in Benin is under threat due to fruit fly infestation on important crops such as cucurbits and mango. Given the economic losses due to fruit fly infestations, population dynamics of fruit flies on these crops were monitored over 6 years (2004–2010) using three parapheromones—cuelure, methyl eugenol and terpinyl acetate. A total of 2,714,186 specimens belonging to 14 species in four genera (Bactrocera, Ceratitis, Dacus and Zeugodacus) were collected. Bactrocera dorsalis was the dominant species that accounted for 89%, 89.6% and 77.2% of captures in the Forest Savannah Mosaic (FSM), Southern Guinea Savannah (SGS) and Northern Guinea Savannah (NGS) agro-ecosystems, respectively. Shannon index values of species diversity differed significantly among agro-ecosystems, with highest diversity in FSM followed by SGS and NGS. Temperature, rainfall and relative humidity (RH) positively influenced the abundance of Dacus species and Zeugodacus cucurbitae across the three agro-ecosystems. Monthly mean temperatures were in a range suitable for development and reproduction of fruit flies, although minimum temperatures could be below such range, which may explain the lower abundance of fruit fly populations during this period of the year. The abundance of B. dorsalis was negatively correlated with maximum temperature and positively correlated with RH and rainfall. Ceratitis species assemblages were significantly affected by minimum temperatures, rainfall and agro-ecosystem. Populations of B. dorsalis and Ceratitis cosyra dropped drastically in August, while those of Z. cucurbitae and Dacus punctatifrons increased sharply from August. Results of this study provide a platform for developing a comprehensive and sustainable management strategy for B. dorsalis and other fruit flies in the three agro-ecosystems to protect the horticulture industry in Benin.

AIDS is a pandemic disease caused by HIV that affects 37 million people worldwide. Current antiretroviral therapy slows disease progression but does not eliminate latently infected cells, which resupply active virus, thus necessitating lifelong treatment with associated compliance, cost, and chemoexposure issues. Latency-reversing agents (LRAs) activate these cells, allowing for their potential clearance, thus presenting a strategy to eradicate the infection. Protein kinase C (PKC) modulators-including prostratin, ingenol esters, bryostatin, and their analogs-are potent LRAs in various stages of development for several clinical indications. While LRAs are promising, a major challenge associated with their clinical use is sustaining therapeutically meaningful levels of the active agent while minimizing side effects. Here we describe a strategy to address this problem based on LRA prodrugs, designed for controllable release of the active LRA after a single injection. As intended, these prodrugs exhibit comparable or superior in vitro activity relative to the parent compounds. Selected compounds induced higher in vivo expression of CD69, an activation biomarker, and, by releasing free agent over time, significantly improved tolerability when compared to the parent LRAs. More generally, selected prodrugs of PKC modulators avoid the bolus toxicities of the parent drug and exhibit greater efficacy and expanded tolerability, thereby addressing a longstanding objective for many clinical applications.

HIV latency prevents cure of infection with antiretroviral therapy (ART) alone. One strategy for eliminating latently infected cells involves the induction of viral protein expression via latency-reversing agents (LRAs), allowing killing of host cells by viral cytopathic effects or immune effector mechanisms. Here, we combine a barcoded HIV approach and a humanized mouse model to study the effects of a designed, synthetic protein kinase C modulating LRA on HIV rebound. We show that administration of this compound during ART results in a delay in rebound once ART is stopped. Furthermore, the rebounding virus appears composed of a smaller number of unique barcoded viruses than occurs in control-treated animals, suggesting that some reservoir cells that would have contributed virus to the rebound process are eliminated by LRA administration. These data support the use of barcoded virus to study rebound and suggest that LRAs may be useful in HIV cure efforts.

Bryostatin 1 is a marine natural product under investigation for HIV/AIDS eradication, the treatment of neurological disorders, and enhanced CAR T/NK cell immunotherapy. Despite its promising activity, bryostatin 1 is neither evolved nor optimized for the treatment of human disease. Here we report the design, synthesis, and biological evaluation of several close-in analogs of bryostatin 1. Using a function-oriented synthesis approach, we synthesize a series of bryostatin analogs designed to maintain affinity for bryostatin's target protein kinase C (PKC) while enabling exploration of their divergent biological functions. Our late-stage diversification strategy provides efficient access to a library of bryostatin analogs, which per our design retain affinity for PKC but exhibit variable PKC translocation kinetics. We further demonstrate that select analogs potently increase cell surface expression of CD22, a promising CAR T cell target for the treatment of leukemias, highlighting the clinical potential of bryostatin analogs for enhancing targeted immunotherapies.

"Shock and kill" strategies focus on purging the latent HIV-1 reservoir by treating infected individuals with therapeutics that activate the latent virus and subsequently eliminating infected cells. We have previously reported that induction of non-canonical nuclear factor κB (NF-κB) signaling through a class of small-molecule antagonists known as Smac mimetics can reverse HIV-1 latency. Here, we describe the development of Ciapavir (SBI-0953294), a molecule specifically optimized for HIV-1 latency reversal that was found to be more efficacious as a latency-reversing agent than other Smac mimetics under clinical development for cancer. Critically, this molecule induced activation of HIV-1 reservoirs in vivo in a bone marrow, liver, thymus (BLT) humanized mouse model without mediating systemic T cell activation. This study provides proof of concept for the in vivo efficacy and safety of Ciapavir and indicates that Smac mimetics can constitute a critical component of a safe and efficacious treatment strategy to eliminate the latent HIV-1 reservoir.

HIV is difficult to eradicate due to the persistence of a long-lived reservoir of latently infected cells. Previous studies have shown that natural killer cells are important to inhibiting HIV infection, but it is unclear whether the administration of natural killer cells can reduce rebound viremia when anti-retroviral therapy is discontinued. Here we show the administration of allogeneic human peripheral blood natural killer cells delays viral rebound following interruption of anti-retroviral therapy in humanized mice infected with HIV-1. Utilizing genetically barcoded virus technology, we show these natural killer cells efficiently reduced viral clones rebounding from latency. Moreover, a kick and kill strategy comprised of the protein kinase C modulator and latency reversing agent SUW133 and allogeneic human peripheral blood natural killer cells during anti-retroviral therapy eliminated the viral reservoir in a subset of mice. Therefore, combinations utilizing latency reversal agents with targeted cellular killing agents may be an effective approach to eradicating the viral reservoir.