The Discussion of Material Basis and Mechanism of Action of Qingre Huashi Kangdu Prescription on the Treatment of COVID-19 Based on Network Pharmacology and Molecular Docking

Objective: To explore the material basis of potential effect and possible molecular mechanisms of Qingre huashi kangdu prescription proposed by Chinese medicine master Wu Bing-cai on the treatment of Corona Virus Disease 2019(COVID-19), and to provide reference for the treatment and scientific research of COVID-19 in traditional Chinese medicine. Method(s): TCMSP, Batman and other databases were used to search chemical components and action targets in traditional Chinese medicines of Qingre huashi kangdu prescription.The disease targets of COVID-19 were screened out by GeneCards, OMIM, GEO databases.Cytoscape software was used to construct the "drugs-components-targets-diseases" network and the interaction relationship between potential targets.Metascape enrichment analysis was used to predict the core modules and mechanism of action, and ACE2 was docking with the main components. Result(s): 202 kinds of chemical components and 301 drug targets in the Qingre huashi kangdu prescription were excavated, there were 360 COVID-19 related disease targets, and 64 intersections of the two.Nine main chemical components were found in the formula, and the key targets involved PTGS2, NOS2, PPARG, MAPK14, NOS3, RELA, etc.Three core modules were predicted, and the core terms mainly included infectious diseases, immune diseases and pathways, immune and inflammatory pathways.A total of 196 items were obtained by GO enrichment analysis, which mainly involved cytokine-mediated signaling pathway, response to oxidative stress, apoptosis signaling pathway, regulation of protein localization establishment, reactive oxygen metabolism, 147 signaling pathways were screened out by KEGG pathway enrichment, including AGE-RAGE signaling pathway in diabetes complications, toxoplasmosis, apoptosis, MAPK signaling pathway, amoebiasis, HIF-1 signaling pathway and RIG-I-like signaling pathway.Molecular docking showed that luteolin, quercetin, baicalein, kaempferol, robinin, wogonin and naringenin had good binding abilities with ACE2, and the combination of quercetin, baicalein and kaempferol with ACE2 was more stable. Conclusion(s): Qingre huashi kangdu prescription treats COVID-19 through multi-components, multi-targets and multi-pathways. Copyright © 2021, Central Station of Chinese Medicinal Materials Information, National Medical Products Administration. All right reserved.

Clinical Characteristics and Outcomes of Critically Ill COVID-19 Patients That Required Continuous Renal Replacement Therapy With and Without Adjuvant Blood Purification

Background: oXiris use received EUA by the FDA as a blood purification adjuvant for COVID-19 critical illness. We evaluated clinical characteristics and outcomes of patients with COVID-19 critical illness that received CRRT with vs. without oXiris. Method(s): Single-center, retrospective cohort study of adult ICU patients with COVID-19 critical illness requiring CRRT (3/2020 to 4/2021). oXiris exposure was defined as a minimum use of 48 h within the first 72 h of CRRT initiation and use of at least 50% of time if the patient died within the first 72 h of CRRT. Data were analyzed with and without propensity-score (PS) matching and with PS-regression. Result(s): 114 critically ill COVID adults admitted to the ICU required CRRT during the study period. Of these, 11 patients used oXiris without meeting the definition of exposure and were excluded. Of the 103 remaining patients, 31 used oXiris and 72 did not. Mean (SD) age of the cohort was 60 (12) years, 66% were male, and 81% white. There were no differences in demographics between both groups. Similarly, there was no difference in baseline kidney function or prevalence of ESRD. Patients that received oXiris had more frequently sepsis (90% vs. 63%, p=0.004) and more frequently received IL-6 inhibitors but CRRT indications were similar in both groups, being the most common one fluid overload in about two-third of patients. Critical illness parameters including SOFA scores (median of 11 in both groups) and extracorporeal organ support (ECMO or mechanical ventilation) were also similar in both groups. Inpatient mortality was not different between both groups (74% in the oXiris group vs. 65% in the non-oXiris group, p=0.37). Further, 28-day ventilator, CRRT and ICU free-days were comparable in both groups. Similarly, kidney recovery rates were not different based on oXiris exposure. These results were consistent in all adjusted analyses. There were no circuit or filter related complications attributed to oXiris. Conclusion(s): The use of oXiris as adjuvant treatment of blood purification during CRRT appears feasible and safe. We did not observe differences in mortality, kidney recovery, or resource utilization among patients exposed vs. non-exposed to oXiris. The clinical impact of oXiris needs to be further evaluated in interventional studies.

[Thoughts and suggestions on co-administration of seasonal influenza vaccine and COVID-19 vaccine].

In the context of the global pandemic of COVID-19, the epidemic intensity, epidemic characteristics and infection risk of influenza have presented new features. COVID-19 and influenza have simultaneously emerged in many regions of the world. COVID-19 and influenza are similar in terms of transmission mode, clinical symptoms and other aspects. There are also similarities in the mechanism of influenza virus and novel coronavirus on cells. At the same time, it is feasible and significant to do a good job in the prevention and control of COVID-19 and influenza. This paper discusses the relevant strategies and measures for the joint prevention and control of influenza and novel coronavirus from the aspects of influenza vaccination to prevent co-infection, simultaneous vaccination of influenza vaccine and novel coronavirus vaccine, etc., and puts forward corresponding thoughts and suggestions, in order to provide scientific support for the formulation of strategies on seasonal influenza vaccine and novel coronavirus vaccination.

Evolution of the emergency drug innovation network and policy implications: Evidence from COVID-19 drug patents

Developing emergency drugs in time is key to responding to public health emergencies such as the coronavirus disease 2019 (COVID-19) pandemic. This research constructs patent assignee citation networks based on COVID-19 drug patents and applies technology life cycle analysis and social network analysis to examine these networks. The results reveal the evolution and structure of the emergency drug innovation network and identify innovation entities with different research and development (R&D) capabilities or a foundation for cooperation. This study attempts to provide the basis for theories and policies to accelerate R&D of emergency drugs. The key results are as follows: (1) Technologies of the emergency drug innovation network show fluctuating growth aligned closely with public health emergencies. (2) The network presents a sparse structure with many active factions, whose members have the advantage of cooperating. (3) Three types of innovation entities are identified: the main technology suppliers, potential suppliers of other supporting technologies, and peripheral suppliers of other supporting technologies.

[Progress on clinical trials of cancer drugs in China, 2020].

Objective: To explore the latest progress of oncology drug clinical trials in China under COVID-19, as well as to provide decision-making evidence for related stakeholders. Research progress of oncology drug trials and approved cancer drugs in China in 2020 were systematically summarized and compared with 2019. Methods: Information Disclosure Platform for Drug Clinical Studies and China Food and Drug Administration Query System for Domestic and Imported Drug were searched for registered clinical trials and approved oncology drugs, respectively. The trial scope, stage, drug type, effect and mechanism of domestic and global pharmaceutical enterprises were compared between 2019 and 2020. Results: A total of 722 cancer drug trials registered in China in 2020, with an annual growth rate of 52.3%, accounting for 28.3% of all registered trials. Among them, 603 (83.5%) trials were initiated by domestic pharmaceutical enterprises, and 105 (14.5%) were international multicenter trials, phase I trials accounted for 44.5%. For all those trials, there were 458 cancer drug varieties, with an annual growth rate of 36.7%, and 361 (85.8%) were developed by domestic enterprises. Most of the investigational products were therapeutic innovative drugs (77.1%), major in tumor treatment (92.8%). In terms of mechanism, targeted drugs were the most popular, accounting for 76.6%, and programmed cell death-1 (PD-1) and epithelial growth factor receptor (EGFR) were the most common targets. In addition, there were 19 anticancer drugs from 17 companies approved in China in 2019, with 10 drugs from domestic companies. Lung cancer and breast cancer are the most common indications for both registered trials and marketed drugs. No statistically significant differences were found between 2020 and 2019 in terms of the distribution of trial sponsor, scope and stage, as well as the distribution of drug type, effect and mechanism (P>0.05). Conclusions: During the Covid-19 epidemic period, clinical trials of oncology drugs in China progress smoothly and maintain a high growth rate. Series of innovative products obtained by domestic enterprises in 2020 is the main driving force of development of oncology drug clinical trials in China.

Emerging infectious diseases and new vaccine technologies

Since the beginning of this century, diverse infectious diseases that threaten human health and social stability have outbroken, such as Ebola hemorrhagic fever, severe respiratory syndrome caused by coronavirus infection, Middle East respiratory syndrome, COVID-19, and Zika viral disease. For the emerging pathogens that have not been characterized, especially viral pathogens with high mutation rate, wide range of host and strong transmission ability, it is impossible to make an effective prediction of the outbreak by now. At present, there is no specific antiviral drug for the infection of these viruses mentioned above, so vaccination is the most cost-effective strategy for preventing and controlling the epidemic. This review aims at providing an overview of the characteristics of Ebola virus, coronavirus, Zika virus, and the research progress of nucleic acid-based (DNA and mRNA) vaccines and viral vector vaccines to combat the infection of these viruses.