Reversible and irreversible inhibitors of coronavirus Nsp15 endoribonuclease.

The emergence of severe acute respiratory syndrome coronavirus 2, the causative agent of coronavirus disease 2019, has resulted in the largest pandemic in recent history. Current therapeutic strategies to mitigate this disease have focused on the development of vaccines and on drugs that inhibit the viral 3CL protease or RNA-dependent RNA polymerase enzymes. A less-explored and potentially complementary drug target is Nsp15, a uracil-specific RNA endonuclease that shields coronaviruses and other nidoviruses from mammalian innate immune defenses. Here, we perform a high-throughput screen of over 100,000 small molecules to identify Nsp15 inhibitors. We characterize the potency, mechanism, selectivity, and predicted binding mode of five lead compounds. We show that one of these, IPA-3, is an irreversible inhibitor that might act via covalent modification of Cys residues within Nsp15. Moreover, we demonstrate that three of these inhibitors (hexachlorophene, IPA-3, and CID5675221) block severe acute respiratory syndrome coronavirus 2 replication in cells at subtoxic doses. This study provides a pipeline for the identification of Nsp15 inhibitors and pinpoints lead compounds for further development against coronavirus disease 2019 and related coronavirus infections.

Clarified sludge (basic oxygen furnace sludge)--an adsorbent for removal of Pb(II) from aqueous solutions--kinetics, thermodynamics and desorption studies.

The basic oxygen furnace waste generated in steel plant has been used as a low cost adsorbent for the removal of Pb(II) from aqueous solution. The effect of pH, adsorbent dosage, initial metal ion concentration, contact time and temperature on adsorption process was studied in batch experiments. Results of the equilibrium experiments showed that the solution pH was the key factor affecting the adsorption characteristics. Optimum pH for the adsorption was found to be 5 with corresponding adsorbent dosage level of 5 g/L. The equilibrium was achieved within 1h of contact time. Kinetics data were best described by pseudo second order model. The effective particle diffusion coefficient of Pb(II) is the order of 10(-10)m(2)/s. The maximum uptake was 92.5mg/g. The adsorption data can be well fitted by Freundlich isotherm. The result of the equilibrium studies showed that the solution pH was the key factor affecting the adsorption. External mass transfer analysis was also carried out for the adsorption process. The thermodynamic studies indicated that the adsorption is spontaneous and endothermic. The sorption energy (10.1745 kJ/mol) calculated from Dubinin-Radushkevich isotherm indicated that the adsorption process is chemical in nature. Desorption studies were carried out using dilute mineral acids to elucidate the mechanism of adsorption. Application studies were carried out considering the economic viewpoint of wastewater treatment plant operations.

Adsorption of Cd(II) and Pb(II) from aqueous solutions on activated alumina.

The ability of activated alumina as synthetic adsorbent was investigated for adsorptive removal of Cd(II) and Pb(II) ions from aqueous solutions. Various physico-chemical parameters such as pH, initial metal ion concentration, and adsorbent dosage level and equilibrium contact time were studied. The optimum solution pH for adsorption of Cd(II) and Pb(II) from aqueous solutions was found to be 5. Kinetics data were best described by pseudo-second order model. The effective particle diffusion coefficient of Cd(II) and Pb(II) are of the order of 10(-10) m(2)/s. Values of mass transfer coefficient were estimated as 4.868x10(-6) cm/s and 6.85x10(-6) cm/s for Cd(II) and Pb(II) adsorption respectively. The equilibrium adsorption data for Cd(II) and Pb(II) were better fitted to Langmuir adsorption isotherm model. The thermodynamic studies indicated that the adsorption was spontaneous and exothermic for Cd(II) adsorption and endothermic for Pb(II). The sorption energy calculated from Dubinin-Radushkevich isotherm were 11.85 kJ/mol and 11.8 kJ/mol for the adsorption of Cd(II) and Pb(II) respectively which indicated that both the adsorption processes were chemical in nature. Desorption studies were carried out using dilute mineral acids. Application studies carried out using industrial waste water samples containing Cd(II) and Pb(II) showed the suitability of activated alumina in waste water treatment plant operation.

The sorption of lead(II) ions on rice husk ash.

Present study deals with the adsorption of Pb(II) from aqueous solution on rice husk ash. Rice husk is a by-product generally obtained from rice mill. Rice husk ash is a solid obtained after burning of rice husk. Batch studies were performed to evaluate the influences of various experimental parameters like pH, initial concentration, adsorbent dosage, contact time and the effect of temperature. Optimum conditions for Pb(II) removal were found to be pH 5, adsorbent dosage 5 g/L of solution and equilibrium time 1h. Adsorption of Pb(II) followed pseudo-second-order kinetics. The effective diffusion coefficient is of the order of 10(-10)m(2)/s. The equilibrium adsorption isotherm was better described by Freuindlich adsorption isotherm model. The adsorption capacity (q(max)) of rice husk ash for Pb(II) ions in terms of monolayer adsorption was 91.74 mg/g. The change of entropy (DeltaS(0)) and enthalpy (Delta H(0)) were estimated at 0.132 kJ/(mol K) and 28.923 kJ/mol respectively. The negative value of Gibbs free energy (Delta G(0)) indicates feasible and spontaneous adsorption of Pb(II) on rice husk ash. The value of the adsorption energy (E), calculated using Dubinin-Radushkevich isotherm, was 9.901 kJ/mol and it indicated that the adsorption process was chemical in nature. Application study was also carried out to find the suitability of the process in waste water treatment operation.