The year's new drugs and biologics 2019

Graul, A.; Pina, Patricia; Tracy, Melissa; Sorbera, L. A.

doi:10.1358/dot.2020.56.1.3129707

Cited by 5 publications

(4 citation statements)

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“…These fears were exacerbated with the 2018–2020 EBOV outbreak in the Democratic Republic of Congo (> 2,200 fatalities) as well as a small outbreak there in 2021. The FDA recently approved an EBOV vaccine and a monoclonal antibody cocktail (Graul et al , 2020; Mullard, 2020); however, the duration and breadth of these outbreaks and that of SARS‐CoV‐2 underscore the dangers of reoccurring outbreaks and the imminent need to develop small molecule counter measures to treat patients who test positive for EBOV. Further, there is still a large gap in knowledge in how EBOV hijacks host cell components to replicate and spread from cell‐to‐cell, elucidation of which may identify new drug targets.…”

Section: Introductionmentioning

confidence: 99%

Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding

et al. 2022

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Phosphatidylserine (PS) is a critical lipid factor in the assembly and spread of numerous lipid‐enveloped viruses. Here, we describe the ability of the Ebola virus (EBOV) matrix protein eVP40 to induce clustering of PS and promote viral budding in vitro, as well as the ability of an FDA‐approved drug, fendiline, to reduce PS clustering and subsequent virus budding and entry. To gain mechanistic insight into fendiline inhibition of EBOV replication, multiple in vitro assays were run including imaging, viral budding and viral entry assays. Fendiline lowers PS content in mammalian cells and PS in the plasma membrane, where the ability of VP40 to form new virus particles is greatly lower. Further, particles that form from fendiline‐treated cells have altered particle morphology and cannot significantly infect/enter cells. These complementary studies reveal the mechanism by which EBOV matrix protein clusters PS to enhance viral assembly, budding, and spread from the host cell while also laying the groundwork for fundamental drug targeting strategies.

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Section: Introductionmentioning

confidence: 99%

Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding

et al. 2022

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“…Due to the emergence of more sophisticated ways to attack diseases over the last decades, the therapeutic area has been enriched of many different sectors of activity, including siRNA, shRNA, miRNA, aptamers, antibodies, and engineered T-cells, to name only but a few. [1][2][3][4][5][6] Thus, from an almost-all small molecule approach to drugs, there has been a dramatic shift in increasing the interest of the Pharma Industry for bigger objects named "Biologics. "…”

Section: Introductionmentioning

confidence: 99%

Biochemistry, structure, and cellular internalization of a four nanobody‐bearing Fc dimer

et al. 2021

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VHH stands for the variable regions of heavy chain only of camelid IgGs. The VHH family forms a set of interesting proteins derived from antibodies that maintain their capacity to recognize the antigen, despite their relatively small molecular weight (in the 12,000 Da range). Continuing our exploration of the possibilities of those molecules, we chose to design alternative molecules with maintained antigen recognition, but enhanced capacity, by fusing four VHH with one Fc, the fragment crystallizable region of antibodies. In doing so, we aimed at having a molecule with superior quantitative antigen recognition (×4) while maintaining its size below the 110 kDa. In the present paper, we described the building of those molecules that we coined VHH2‐Fc‐VHH2. The structure of VHH2‐Fc‐VHH2 in complex with HER2 antigen was determined using electronic microscopy and modeling. The molecule is shown to bind four HER2 proteins at the end of its flexible arms. VHH2‐Fc‐VHH2 also shows an internalization capacity via HER2 receptor superior to the reference anti‐HER2 monoclonal antibody, Herceptin®, and to a simple fusion of two VHH with one Fc (VHH2‐Fc). This new type of molecules, VHH2‐Fc‐VHH2, could be an interesting addition to the therapeutic arsenal with multiple applications, from diagnostic to therapy.

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“…This annual review, which is now in its 17th installment, 2 presents synthetic routes for 31 new molecular entities that were approved for the first time by a governing body anywhere in the world during the 2017 calendar year (Figure 1). 3 For each drug, a description of the most likely process-scale synthetic approach, or in some cases the only publicly disclosed synthetic approach, is prefaced by a brief introduction summarizing the relevant pharmacology or differentiating features of the medicine. 4 In all cases, descriptions of the syntheses begin with commercially available starting materials.…”

Section: Introductionmentioning

confidence: 99%