The SARS-CoV-2 replication-transcription complex is a priority target for broad-spectrum pan-coronavirus drugs

In the absence of effective treatment, COVID-19 is likely to remain a global disease burden. Compounding this threat is the near certainty that novel coronaviruses with pandemic potential will emerge in years to come. Pan-coronavirus drugs - agents active against both SARS-CoV-2 and other coronaviruses - would address both threats. A strategy to develop such broad-spectrum inhibitors is to pharmacologically target binding sites on SARS-CoV-2 proteins that are highly conserved in other known coronaviruses, the assumption being that any selective pressure to keep a site conserved across past viruses will apply to future ones. Here, we systematically mapped druggable binding pockets on the experimental structure of fifteen SARS-CoV-2 proteins and analyzed their variation across twenty-seven - and {beta}-coronaviruses and across thousands of SARS-CoV-2 samples from COVID-19 patients. We find that the two most conserved druggable sites are a pocket overlapping the RNA binding site of the helicase nsp13, and the catalytic site of the RNA-dependent RNA polymerase nsp12, both components of the viral replication-transcription complex. We present the data on a public web portal (https://www.thesgc.org/SARSCoV2_pocketome/) where users can interactively navigate individual protein structures and view the genetic variability of drug binding pockets in 3D.

Study on the Acute Eye Toxicity of PP1 Liposomes / 中国药师

Objective:To observe the acute toxic side effects of liposome PP 1 topically applied in eyes .Methods:PP1 liposomes (10, 60, 400 μmol· L-1 ) were used in one eye of SD rats , 4 times daily.The changes of conjunctiva , cornea and iris were observed under the slit-lamp biomicroscope , for three consecutive days , and evaluated by the stimulus score sheet of anterior segment .One week after the treatment , the corneas , irises and lenses were isolated , and their changes were observed under the light microscope .The ul-trastructural changes of corneal epithelial cells and endothelial cells were observed under the electron microscope .Results:There was a little of conjunctival secretion in one rat in the first day after the treatment with 400 μmol· L-1 PP1 liposomes, and the other rats were not irritant reaction .The corneal fluorescein staining of all rats were negative .The structures of cornea , iris, lens tissue were normal after given different concentrations of PP1 liposomes.Conclusion:PP1 liposomes at Low, medium and high concentrations show no a-cute eye toxicity in SD rats .