Progress in drug development for treatment of coronavirus disease 2019 (COVID-19)

Since the outbreak of the novel coronavirus (SARS-CoV-2), the number of people infected worldwide has been increasing, and the medical situation is very severe. In emergency situations, the development of innovative drugs and the treatment of new coronavirus pneumonia (COVID-19) new adaptations on the market The development of the certificate has become the only way to find specific therapeutic drugs and the best treatment plan for COVID-19. The mechanism of angiotensin-converting enzyme 2 (ACE2) that mediates the invasion of host cells by SARS-CoV-2 has been discovered and is based on SARS-CoV- 2. Potential therapeutic targets of host and host, mainly including RNA-dependent RNA polymerase, 3CL protease, papain-like protease, Janus kinase, interleukin 6 and immunomodulators, etc. According to the above-mentioned pharmacological mechanism of action, the treatment of marketed drugs Great progress has been made in the development of new indications for COVID-19 and the clinical research and development of innovative drugs, but no specific drugs have been found. Some traditional Chinese medicines in China can block the SARS-CoV-2 replication cycle, regulate the body's immune response, and treat COVID-19. Biopharmaceuticals are currently undergoing phase I clinical studies in the world for the treatment of COVID-19. Biopharmaceuticals are progressing rapidly, accounting for 67%. At present, the research and development of drugs for the treatment of COVID-19 in China is facing severe challenges and biosafety The number of protection laboratories is small, the research on the mechanism of SARS-CoV-2 infection and the body's response mechanism is not in-depth, the resources of non-clinical cells and animal models are scarce, and the professional quantitative pharmacology research platform and professional talent training system are not perfect to treat COVID-19 The informatization of drug clinical trials and sample testing capabilities are in urgent need of improvement. If China can use this to improve its ability to develop new drugs in emergency situations, it will be able to better protect people's health.

Exploring the effectiveness of the TSR-based protein 3-D structural comparison method for protein clustering, and structural motif identification and discovery of protein kinases, hydrolases, and SARS-CoV-2's protein via the application of amino acid grouping.

Development of protein 3-D structural comparison methods is essential for understanding protein functions. Some amino acids share structural similarities while others vary considerably. These structures determine the chemical and physical properties of amino acids. Grouping amino acids with similar structures potentially improves the ability to identify structurally conserved regions and increases the global structural similarity between proteins. We systematically studied the effects of amino acid grouping on the numbers of Specific/specific, Common/common, and statistically different keys to achieve a better understanding of protein structure relations. Common keys represent substructures found in all types of proteins and Specific keys represent substructures exclusively belonging to a certain type of proteins in a data set. Our results show that applying amino acid grouping to the Triangular Spatial Relationship (TSR)-based method, while computing structural similarity among proteins, improves the accuracy of protein clustering in certain cases. In addition, applying amino acid grouping facilitates the process of identification or discovery of conserved structural motifs. The results from the principal component analysis (PCA) demonstrate that applying amino acid grouping captures slightly more structural variation than when amino acid grouping is not used, indicating that amino acid grouping reduces structure diversity as predicted. The TSR-based method uniquely identifies and discovers binding sites for drugs or interacting proteins. The binding sites of nsp16 of SARS-CoV-2, SARS-CoV and MERS-CoV that we have defined will aid future antiviral drug design for improving therapeutic outcome. This approach for incorporating the amino acid grouping feature into our structural comparison method is promising and provides a deeper insight into understanding of structural relations of proteins.

Clinical Characteristics of Non-Pneumonia COVID-19 Adults in Shanghai, China (preprint)

Background: Since December 2019, coronavirus disease 2019 (COVID-19) rapidly spread throughout the whole world , data have been needed on the clinical characteristics of the affected patients.Objectives: A total of 579 adult COVID-19 cases were enrolled in Shanghai from Jan 20 to Apr 15, 2020, in which 95 cases (16.41%) showed non-pneumonia on CT when confirmed. The characteristics of non-pneumonia cases have not been clearly described previously, and this might provide guidance to prevent and treatment of COVID-19.Method: We retrospectively collected the patient clinical dataset including demography, epidemiology, clinical manifestation, laboratory test results, diagnostic classification, treatment and clinical outcomes.Results: The average age of 95 COVID-19 cases was 31.45 ± 12.89 years old and 95.79% of them were less than 60 years old. They had mild clinical symptoms and/or laboratory abnormalities. 20 of the 95 cases occurred mild pneumonia during hospitalization, accompanied with lower lymphocyte counts, in which 60% cases were complicated with underlying condition and 15% cases were over 60 years old. All cases were cured. 16 of the 95 cases were local residents with clear epidemiological history and long incubation time, and mainly discovered as fever and respiratory symptoms. Other 79 cases were overseas imported, some had initial symptoms of diarrhea, smell or taste disorders and so on. They were mainly found at port of entry.Conclusions: Non-pneumonia COVID-19 predominantly occurred among young adults with mild clinical symptoms and possible long incubation time. The patients with underlying condition or at older age more likely developed mild pneumonia after diagnosis. Thereby, it is very important to pay attention to these patients and make reasonable diagnostic classification towards better prevention and treatment of COVID-19.