Discovery of Hepatitis B Virus Surface Antigen Suppressor GS-8873.

Chronic hepatitis B (CHB) virus infection afflicts hundreds of millions of people and causes nearly one million deaths annually. The high levels of circulating viral surface antigen (HBsAg) that characterize CHB may lead to T-cell exhaustion, resulting in an impaired antiviral immune response in the host. Agents that suppress HBsAg could help invigorate immunity toward infected hepatocytes and facilitate a functional cure.

Interaction analysis of tobacco leaf microbial community structure and volatiles flavor compounds during cigar stacking fermentation.

Introduction: Cigar stacking fermentation is a key step in tobacco aroma enhancement and miscellaneous gas reduction, which both have a great influence on increasing cigar flavor and improving industrial availability.

Methods: To analyze the effect of cigar tobacco leaf (CTLs) microbial community on volatiles flavor compounds (VFCs), this study used multi-omics technology to reveal the changes in microbial community structure and VFCs of different cigar varieties during stacking fermentation, in addition to exploring the interaction mechanism of microbiome and VFCs.

Results: The results showed that the dominant microbial compositions of different CTL varieties during stacking fermentation were similar, which included , , , and .

Effects of Inoculation With on Fermentation of Cigar Tobacco Leaves.

Metabolic activity of the microbial community greatly affects the quality of cigar tobacco leaves (CTLs). To improve the quality of CTLs, two extrinsic microbes ( sp. 1H8 and 3B2) were inoculated into CTLs.

Clinical targeting of HIV capsid protein with a long-acting small molecule.

Oral antiretroviral agents provide life-saving treatments for millions of people living with HIV, and can prevent new infections via pre-exposure prophylaxis. However, some people living with HIV who are heavily treatment-experienced have limited or no treatment options, owing to multidrug resistance. In addition, suboptimal adherence to oral daily regimens can negatively affect the outcome of treatment-which contributes to virologic failure, resistance generation and viral transmission-as well as of pre-exposure prophylaxis, leading to new infections.

Highly potent HCV NS4B inhibitors with activity against multiple genotypes.

The exploration of novel inhibitors of the HCV NS4B protein that are based on a 2-oxadiazoloquinoline scaffold is described. Optimization to incorporate activity across genotypes led to a potent new series with broad activity, of which inhibitor 1 displayed the following EC50 values: 1a, 0.08 nM; 1b, 0.

Discovery of GS-9451: an acid inhibitor of the hepatitis C virus NS3/4A protease.

The discovery of GS-9451 is reported. Modification of the P3 cap and P2 quinoline with a series of solubilizing groups led to the identification of potent HCV NS3 protease inhibitors with greatly improved pharmacokinetic properties in rats, dogs and monkeys.

Discovery of GS-9256: a novel phosphinic acid derived inhibitor of the hepatitis C virus NS3/4A protease with potent clinical activity.

A potent and novel class of phosphinic acid derived product-like inhibitors of the HCV NS3/4A protease was discovered previously. Modification of the phosphinic acid and quinoline heterocycle led to GS-9256 with potent cell-based activity and favorable pharmacokinetic parameters. Based on these attributes, GS-9256 was advanced to human clinical trial as a treatment for chronic infection with genotype 1 HCV.

Reversible guest molecule encapsulation in the 3-D framework of a heteropolynuclear luminescent Zn4Eu2 cage complex.

Guest molecules of diethyl ether or methanol are reversibly encapsulated in cavities formed by the 3-dimensional supramolecular framework of heteropolynuclear, luminescent [Eu2Zn4L4(OAc)6(NO3)2(OH)2].2Et2O.

Catalytic signal amplification using a Heck reaction. An example in the fluorescence sensing of CuII.

Catalytic signal enhancement using an organometallic reaction is demonstrated. The reactivity of a Heck cross-coupling reaction that creates a fluorophore is modulated by the addition of a polyazacyclam inhibitor. The inhibitor will complex with Cu(II), which restores the activity of the Pd(II).