Computationally restoring the potency of a clinical antibody against Omicron.

The COVID-19 pandemic underscored the promise of monoclonal antibody-based prophylactic and therapeutic drugs and revealed how quickly viral escape can curtail effective options. When the SARS-CoV-2 Omicron variant emerged in 2021, many antibody drug products lost potency, including Evusheld and its constituent, cilgavimab. Cilgavimab, like its progenitor COV2-2130, is a class 3 antibody that is compatible with other antibodies in combination and is challenging to replace with existing approaches.

Computationally restoring the potency of a clinical antibody against SARS-CoV-2 Omicron subvariants.

The COVID-19 pandemic underscored the promise of monoclonal antibody-based prophylactic and therapeutic drugs, but also revealed how quickly viral escape can curtail effective options. With the emergence of the SARS-CoV-2 Omicron variant in late 2021, many clinically used antibody drug products lost potency, including Evusheld and its constituent, cilgavimab. Cilgavimab, like its progenitor COV2-2130, is a class 3 antibody that is compatible with other antibodies in combination and is challenging to replace with existing approaches.

Prospects for Fungal Bioremediation of Acidic Radioactive Waste Sites: Characterization and Genome Sequence of MD1149.

Highly concentrated radionuclide waste produced during the Cold War era is stored at US Department of Energy (DOE) production sites. This radioactive waste was often highly acidic and mixed with heavy metals, and has been leaking into the environment since the 1950s. Because of the danger and expense of cleanup of such radioactive sites by physicochemical processes, bioremediation methods are being developed for cleanup of contaminated ground and groundwater.

Rhodotorula taiwanensis MD1149 produces hypoacetylated PEFA compounds with increased surface activity compared to Rhodotorula babjevae MD1169.

Biosurfactants have several desirable characteristics in the industrial sector: detergency, antimicrobial effects, skin hydration, and emulsibility. Several yeast glycolipids are currently being utilized in these capacities: sophorolipids, ustilagic acid, and mannosylerythritol lipids (MELs). An emerging class of glycolipids, termed polyol esters of fatty acids (PEFA), have recently been reported for Rhodotorula babjevae, a basidiomycetous yeast species that secretes hyperacetylated congeners of PEFA (typically with 3-6 acetylation modifications).

Development and Translational Application of an Integrated, Mechanistic Model of Antibody-Drug Conjugate Pharmacokinetics.

Antibody drug conjugates (ADC), in which small molecule cytotoxic agents are non-specifically linked to antibodies, can enable targeted delivery of chemotherapeutics to tumor cells. ADCs are often produced and administered as a mixture of conjugated antibodies with different drug to antibody ratios (DAR) resulting in complex and heterogeneous disposition kinetics. We developed a mechanism-based platform model that can describe and predict the complex pharmacokinetic (PK) behavior of ADCs with protease-cleavable valine-citrulline (VC) linker linked to Monomethylmonomethyl auristatin F/E by incorporating known mechanisms of ADC disposition.