2022/10/21 0:00:00 HU Er-Ya,ZHOU Min,ZENG Wen-Hui,LUO Yan,YAN Zi-Dong and MA Jian 5true 2022/10/21 0:00:00 LIU Xiang,GONG Peng-Yun,TANG Min,HU Hong-Ke,ZHANG Yong-Biao and LIU Chao 4true Objective To investigate the effect of SARS-CoV-2 membrane protein on the processing of the 3" untranslated region (UTR) of the mRNA precursor (pre-mRNA) in host cells.Methods Based on the cell model of human lung epithelial cells A549, over-expression of the SARS-CoV-2 membrane protein was performed. The RNA-Seq high-throughput sequencing technique and bioinformatics methods was employed to analyze the systematic characterization of alternative polyadenylation (APA) events in host cells. Genes with significant APA events were uploaded to the Metascape database for functional enrichment analysis. In addition, alternative 3"UTR length of genes with APA events was verified by RT-qPCR. Then the target protein expression level was detected by Western blot.Results A total of 813 genes that were significant dynamic APA events in host cells that over-expressed SARS-CoV-2 membrane protein. These genes were enriched in cell biologicial processes such as the mitotic cell cycle and regulation of cellular response to stress. We further screened AKT1, which encodes a critical regulator involved in the above biological process, showing a 3"UTR lengthening in IGV software. RT-qPCR verified the trend of 3"UTR length changes of AKT1. Western blot showed the increased level of phosphorylated AKT1 protein in over-expressed group of M protein.Conclusion SARS-CoV-2 membrane protein potentially affects the 3" processing of host pre-mRNAs. AKT1, which is involved in a variety of viral biological processes, with 3"UTR lengthening, and its protein function was activated intracellularly.]]> 2022/10/21 0:00:00 OUYANG Xin,ZENG Xian-Yan,GU Bin,LOU Zhe-Qi,HUANG Jin,TAN Zheng-Zong,YU Qian,CHE Yu,QIAN Yu-Zhou and ZHU Yong 3true Objective Many mutant strains of SARS-CoV-2 have stronger infectivity and immune escape ability. The situation of epidemic evaluation, prevention and control is serious. The aim of the present paper is to track and predict the infectious transmission of COVID-19 through a theoretical model.Methods Based on the grid epidemic model, this paper discussed the relationship between the duration of infection and the effect of group immunity, and on this basis, established the theoretical model of infection transmission of COVID-19. The infectivity parameter A and the immune effect parameter B are introduced to predict the daily variation curve of infection. The parameter can be used to quantitatively compare the comprehensive infectivity of each mutant, and we also test the conjecture that the infection parameters A and B are not related to regional factors.Results Through the theoretical model of infection transmission of COVID-19, the infectious time was accurately predicted. By analyzing the infectivity and electrical changes of mutant strains, the internal relationship between the infectivity of mutant strains and the electrical changes of mutant residues was pointed out. The parameter changes of mutants were analyzed, and the comprehensive infectivity of each mutant was quantitatively compared. We also verified the conjecture that parameters A and B are only related to the nature of the virus itself and the coexistence of the virus and the human body, but not related to the region where the disease occurs and evaluated and compared the epidemic prevention level of each outbreak region.Conclusion This paper established a theoretical model of infection transmission of COVID-19, which can predict the duration of the epidemic, the number of new infections per day, and evaluate the infectivity of the virus, immune escape ability, comprehensive infectivity, and regional epidemic prevention level. It can also give some suggestions on epidemic prevention countermeasures according to the possible parameter changes caused by virus variation.]]> 2022/10/21 0:00:00 Liu Cheng-Fang,Liang Yu-Chao,Zhou Jian,Zuo Yong-Chun and Luo Liao-Fu 2true Objective To detect the active ingredients in the traditional Chinese medicine prescription and its molecular mechanisms against SARS-CoV-2 by prescription mining and molecular dynamics simulations.Methods Herein, prescription mining and virtual screening of drugs were performed to screen the potential inhibitors against SARS-CoV-2. Molecular docking and molecular dynamics (MDs) simulations were further performed to explore the molecular recognition and inhibition mechanism between the potential inhibitors and SARS-CoV-2.Results The natural compounds library was constructed by 143 prescriptions of traditional Chinese medicine, which contained 640 natural compounds. Ten compounds were screened out from the natural compounds library. Among the 10 compounds, 23-trans-p-coumaryhormentic acid, the main active constituent of the Loquat leaf, showed the best binding affinity targeting the recognizing interface of SARS-CoV-2 S protein/ACE2. Upon binding 23-trans-p-coumaryhormentic acid, the key interactions between SARS-CoV-2 S protein and ACE2 were almost interrupted.Conclusion Ten compounds targeting SARS-CoV-2 S protein/ACE2 interface were screened out from natural compound library. And we inferred that 23-trans-p-coumaryhormentic acid is a potential inhibitor against SARS-CoV-2, which would contribute to the development of the antiviral drug for SARS-CoV-2.]]> 2022/10/21 0:00:00 ZHANG Xiao-Zheng,GAO Ying,LIU Yu,TAI Yang-Hao,LIANG Li-Zhong,ZHANG Yu-Long,HOU Shu-Lin and XIE Jun 1true