Mpro-targeted anti-SARS-CoV-2 inhibitor-based drugs.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global health emergency. The main protease is an important drug target in coronaviruses. It plays an important role in the processing of viral RNA-translated polyproteins and is highly conserved in the amino acid sequence and three-dimensional structure, making it a good drug target for which several small molecule inhibitors are available. This paper describes the various anti-severe acute respiratory syndrome coronavirus 2 inhibitor drugs targeting Mpro discovered since the severe acute respiratory syndrome coronavirus 2 outbreak at the end of 2019, with all these compounds inhibiting severe acute respiratory syndrome coronavirus 2 Mpro activity in vitro. This provides a reference for the development of severe acute respiratory syndrome coronavirus 2 Mpro-targeted inhibitors and the design of therapeutic approaches to address newly emerged severe acute respiratory syndrome coronavirus 2 mutant strains with immune evasion capabilities.

Robust Nitritation of Anaerobic Digester Centrate Using Dual Stressors and Timed Alkali Additions.

Nitrogen is commonly removed from wastewater by nitrification to nitrate followed by nitrate reduction to N2. Shortcut N removal saves energy by limiting ammonia oxidation to nitrite, but nitrite accumulation can be unstable. We hypothesized that repeated short-term exposures of ammonia-oxidizing communities to free ammonia (FA) and free nitrous acid (FNA) would stabilize nitritation by selecting against nitrite-oxidizing bacteria (NOB). Accordingly, we evaluated ammonium oxidation of anaerobic digester centrate in two bench-scale sequencing batch reactors (SBRs), seeded with the same inoculum and operated identically but with differing pH-control strategies. A single stressor SBR (SS/SBR) using pH set-point control produced HNO3, while a dual stressor SBR (DS/SBR) using timed alkalinity addition (TAA) produced HNO2 (ammonium removal efficiency of 97 ± 2%; nitrite accumulation ratio of 98 ± 1%). The TAA protocol was developed during an adaptation period with continuous pH monitoring. After adaptation, automated TAA enabled stable nitritation without set-point control. In the SS/SBR, repeatedly exposing the community to FA (8-10 h/exposure, one exposure/cycle) selected for FA-tolerant ammonia-oxidizing bacteria (Nitrosomonas sp. NM107) and NOB (Nitrobacter sp.). In the DS/SBR, repeatedly exposing the community to FA (2-4 h/exposure, three exposures/cycle) and FNA (4-6 h/exposure, two exposures/cycle) selected for FA- and FNA-resistant AOB (Nitrosomonas IWT514) and against NOB, stabilizing nitritation.

Nitrogen removal as nitrous oxide for energy recovery: Increased process stability and high nitrous yields at short hydraulic residence times.

The Coupled Aerobic-anoxic Nitrous Decomposition Operation (CANDO) is a two-stage process for nitrogen removal and resource recovery: in the first, ammonia is oxidized to nitrite in an aerobic bioreactor; in the second, oxidation of polyhydroxyalkanoate (PHA) drives reduction of nitrite to nitrous oxide (N2O) which is stripped for use as a biogas oxidant. Because ammonia oxidation is well-studied, tests of CANDO to date have focused on N2O production in anaerobic/anoxic sequencing batch reactors. In these reactors, nitrogen is provided as nitrite; PHA is produced from acetate or other dissolved COD, and PHA oxidation is coupled to N2O production from nitrite. In a pilot-scale study, N2O recovery was affected by COD/N ratio, total cycle time, and relative time periods for PHA synthesis and N2O production. In follow-up bench-scale studies, different reactor cycle times were used to investigate these operational parameters. Increasing COD/N ratio improved nitrite removal and increased biosolids concentration. Shortening the anaerobic phase prevented fermentation of PHA and improved its utilization. Efficient PHA synthesis and utilization in the anaerobic phase correlated with high N2O production in the anoxic phase. Shortening the anoxic phase prevented reduction of N2O to N2. By shortening both phases, total cycle time was reduced from 24 to 12 h. This optimized operation enabled increased biomass concentrations, increased N2O yields (from 71 to 87%), increased N loading rates (from 0.1 to 0.25 kg N/m3-d), and shorter hydraulic residence times (from 10 to 2 days). Long-term changes in operational performance for the different bioreactor systems tested were generally similar despite significant differences in microbial community structure. Long-term operation at short anaerobic phases selected for a glycogen-accumulating community dominated by a Defluviicoccus-related strain.

Bio-entrapped membrane reactor and salt marsh sediment membrane bioreactor for the treatment of pharmaceutical wastewater: treatment performance and microbial communities.

In this study, a bio-entrapped membrane reactor (BEMR) and a salt marsh sediment membrane bioreactor (SMSMBR) were evaluated to study the organic treatment performance of pharmaceutical wastewater. The influences of hydraulic retention time (HRT) and salinity were also studied. The conventional biomass in the BEMR cannot tolerate well of the hypersaline conditions, resulting in total chemical oxygen demand (TCOD) removal efficiency of 54.2-68.0%. On the other hand, microorganisms in the SMSMBR, which was seeded from coastal shore, strived and was able to degrade the complex organic in the presence of salt effectively, achieving 74.7-90.9% of TCOD removal efficiencies. Marine microorganisms able to degrade recalcitrant compounds and utilize hydrocarbon compounds were found in the SMSMBR, which resulted in higher organic removal efficiency than the BEMR. However, specific nitrifying activity decreased and inhibited due to the saline effect that led to poor ammonia nitrogen removal.