Efficiency Comparison of Public and Private Hospitals before and after the COVID-19 Pandemic: The Case of Hubei, China (preprint)

Background The persistence and spread of the COVID-19 pandemic adversely affected the efficiency of hospitals with different ownership. This article aims to compare the differences and changes in technical efficiency of public and private hospitals before and after the pandemic. Methods We collected institutional and operational data for all 519 general hospitals (including 243 public and 356 private hospitals) in Hubei province China from 2019 to 2021. Using the slacks-based measure model (SBM), we measured and compared technical efficiency. The effect of the pandemic on hospital efficiency was examined with a two-way fixed effect model and a lasso regression model. PSM, Tobit regression was used for robustness testing. Results Public hospitals were much more efficient than private hospitals both before and after the epidemic in Hubei. The mean efficiency score of public and private hospitals was 0.52 and 0.26 in 2019, 0.37 and 0.22 in 2020, 0.44 and 0.24 in 2021. The difference in efficiency between public and private hospitals was significant in 2019 and 2021(p<0.001). Public hospital efficiency showed a faster recovery in the face of the epidemic. Conclusions Public hospitals run by the administrative system have shown greater efficiency and played a major role in the fight against the pandemic. The country's public health protection network should be fortified and efforts should be made to promote the high-quality development of public hospitals. The widening of the overall gap between public and private hospitals appeared. In the post-epidemic era, private hospitals need to prioritize finding the right positioning and offering highly specific medical services in China.

Receptor-binding domain-anchored peptides block binding of severe acute respiratory syndrome coronavirus 2 spike proteins with cell surface angiotensin-converting enzyme 2

Background The COVID-19 pandemic has killed over 6 million people worldwide. Despite the accumulation of knowledge about the causative pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the pathogenesis of this disease, cures remain to be discovered. We searched for certain peptides that might interfere with spike protein (S protein)-angiotensin-converting enzyme 2 (ACE2) interactions. Methods Phage display (PhD)-12 peptide library was screened against recombinant spike trimer (S-trimer) or receptor-binding domain (S-RBD) proteins. The resulting enriched peptide sequences were obtained, and their potential binding sites on S-trimer and S-RBD 3D structure models were searched. Synthetic peptides corresponding to these and other reference sequences were tested for their efficacy in blocking the binding of S-trimer protein onto recombinant ACE2 proteins or ACE2-overexpressing cells. Results After three rounds of phage selections, two peptide sequences (C2, DHAQRYGAGHSG;C6, HWKAVNWLKPWT) were enriched by S-RBD, but only C2 was present in S-trimer selected phages. When the 3D structures of static monomeric S-RBD (6M17) and S-trimer (6ZGE, 6ZGG, 7CAI, and 7CAK, each with different status of S-RBDs in the three monomer S proteins) were scanned for potential binding sites of C2 and C6 peptides, C6 opt to bind the saddle of S-RBD in both 6M17 and erected S-RBD in S-trimers, but C2 failed to cluster there in the S-trimers. In the competitive S-trimer-ACE2-binding experiments, synthetic C2 and C6 peptides inhibited S-trimer binding onto 293T-ACE2hR cells at high concentrations (50 μM) but not at lower concentrations (10 μM and below), neither for the settings of S-trimer binding onto recombinant ACE2 proteins. Conclusion Using PhD methodology, two peptides were generated bearing potentials to interfere with S protein-ACE2 interaction, which might be further exploited to produce peptidomimetics that block the attachment of SARS-CoV-2 virus onto host cells, hence diminishing the pathogenesis of COVID-19.

Several key scientific issues of the new Coronavirus SARS-CoV-2 that need to be clarified urgently

The new coronavirus (SARS-CoV-2) that broke out at the end of 2019 has caused more than 80,000 infections and more than 2,700 deaths worldwide (as of February 25, 2020). Although SARS-CoV-2 and the SARS-CoV that broke out in 2003 belong to the Coronavirus family and beta-coronavirus genus and have high similarities, the whole genome homology is about 79%, but the two have many aspects in terms of disease course and fatality rate. difference. So far, SARS-CoV-2 host (including natural host and intermediate host), transmission route, virulence variation, etc. still need to be clarified urgently. This article will briefly explain some of the above-mentioned scientific problems.

Molecular mechanism of Bufei Huoxue Capsule on COVID-2019 based on network pharmacology and molecular docking

Objective: To explore the potential mechanism of Bufei Huoxue Capsule (BHC) on coronavirus disease 2019 (COVID-19), and provide a theoretical basis for the clinical application of BHC. Methods: TCMSP, BATMAN-TCM, CNKI and Pubmed databases were used to search the compounds and targets of BHC and GeneCards database was used to search the targets of COVID-19;The intersection method was used to obtain the targets related to the therapeutic effect of BHC. Cytoscape 3.7.2 software was applied for the construction of CMM-compounds-targets network map. Protein-protein interaction (PPI) network was constructed by STRING database. Gene ontology (GO) functional enrichment analysis and KEGG pathway enrichment analysis were conducted by DAVID. AutoDock Tools 1.5.6 and AutoDock vina 1.1.2 were used for molecular docking. Results: A total of 32 potential active components were screened from BHC, corresponding to 203 targets. Among them, there were 11 core compounds and 52 core targets. PPI network analysis showed that there were 25 key targets intervening COVID-19 by BHC. A total of 251 biological processes (P < 0.05) and 93 pathways (P < 0.05) were obtained by GO analysis and KEGG analysis, respectively. The results of molecular docking showed that the key compounds had good affinity with SARS-CoV-2 3CL hydrolase and angiotensin converting enzyme II. Conclusion: The active compounds of BHC can target IL6, MAPK8, PTGS2, PTGS1 and NCOA2 to regulate multiple signal pathways, and play a therapeutic role in the recovery period of COVID-19.

TMPRSS2 Protease Inhibitors May Prolong But Heparins Accelerate SARS-CoV-2 Clearance (preprint)

The 2019 novel SARS-like coronavirus (SARS-CoV-2) entry depends on the host membrane serine protease TMPRSS2, which can be blocked by some clinically-proven drugs. Here we analyzed spatial relevance between glycosylation sequons and antibody epitopes and found that, different from SARS-CoV S, most high-surface-accessible epitopes of SARS-CoV-2 S are blocked by the glycosylation, and the optimal epitope with the highest surface accessibility is covered by the S1 cap. TMPRSS2 inhibitor treatments may prevent unmasking of this epitope and therefore prolong virus clearance and may induce antibody-dependent enhancement. Interestingly, a heparin-binding sequence immediately upstream of the S1/S2 cleavage site has been found in SARS-CoV-2 S but not in SARS-CoV S. Binding of SARS-CoV-2 with heparins may lead to exposure of S686, which then facilitates the S1/S2 cleavage, induces exposure of the optimal epitope, and therefore increases the antibody titres. A combination of heparin and vaccine (or convalescent serum) treatments thus is recommended.

Structure of RNA-dependent RNA polymerase from 2019-nCoV, a major antiviral drug target (preprint)

A novel coronavirus (2019-nCoV) outbreak has caused a global pandemic resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase (RdRp, also named nsp12), which catalyzes the synthesis of viral RNA, is a key component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. Here we report the cryo-EM structure of 2019-nCoV full-length nsp12 in complex with cofactors nsp7 and nsp8 at a resolution of 2.9-[A]. Additional to the conserved architecture of the polymerase core of the viral polymerase family and a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain featured in coronaviral RdRp, nsp12 possesses a newly identified {beta}-hairpin domain at its N-terminal. Key residues for viral replication and transcription are observed. A comparative analysis to show how remdesivir binds to this polymerase is also provided. This structure provides insight into the central component of coronaviral replication/transcription machinery and sheds light on the design of new antiviral therapeutics targeting viral RdRp. One Sentence SummaryStructure of 2019-nCov RNA polymerase.