Noncovalent complexation of amphotericin-B with Poly(α-glutamic acid).

A noncovalent complex of amphotericin B (AmB) and poly(α-glutamic acid) (PGA) was prepared to develop a safe and stable formulation for the treatment of leishmaniasis. The loading of AmB in the complex was in the range of ∼20-50%. AmB was in a highly aggregated state with an aggregation ratio often above 2.0. This complex (AmB-PGA) was shown to be stable and to have reduced toxicity to human red blood cells and KB cells compared to the parent compound; cell viability was not affected at an AmB concentration as high as 50 and 200 μg/mL respectively. This AmB-PGA complex retained AmB activity against intracellular Leishmania major amastigotes in the differentiated THP-1 cells with an EC50 of 0.07 ± 0.03-0.08 ± 0.01 μg/mL, which is similar to Fungizone (EC50 of 0.06 ± 0.01 μg/mL). The in vitro antileishmanial activity of the complex against Leishmania donovani was retained after storage at 37 °C for 7 days in the form of a solution (EC50 of 0.27 ± 0.03 to 0.35 ± 0.04 μg/mL) and for 30 days as a solid (EC50 of 0.41 ± 0.07 to 0.63 ± 0.25 μg/mL). These encouraging results indicate that the AmB-PGA complex has the potential for further development

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Noncovalent Complexation of Amphotericin‑B with Poly(α-glutamic acid)

A noncovalent complex of amphotericin B (AmB) and poly­(α-glutamic acid) (PGA) was prepared to develop a safe and stable formulation for the treatment of leishmaniasis. The loading of AmB in the complex was in the range of ∼20–50%. AmB was in a highly aggregated state with an aggregation ratio often above 2.0. This complex (AmB–PGA) was shown to be stable and to have reduced toxicity to human red blood cells and KB cells compared to the parent compound; cell viability was not affected at an AmB concentration as high as 50 and 200 μg/mL respectively. This AmB–PGA complex retained AmB activity against intracellular <i>Leishmania major</i> amastigotes in the differentiated THP-1 cells with an EC₅₀ of 0.07 ± 0.03–0.08 ± 0.01 μg/mL, which is similar to Fungizone (EC₅₀ of 0.06 ± 0.01 μg/mL). The <i>in vitro</i> antileishmanial activity of the complex against <i>Leishmania donovani</i> was retained after storage at 37 °C for 7 days in the form of a solution (EC₅₀ of 0.27 ± 0.03 to 0.35 ± 0.04 μg/mL) and for 30 days as a solid (EC₅₀ of 0.41 ± 0.07 to 0.63 ± 0.25 μg/mL). These encouraging results indicate that the AmB–PGA complex has the potential for further development

COVID-19 Host Genetics Initiative. A first update on mapping the human genetic architecture of COVID-19

The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity.</p