The emergence of the new coronavirus (nCoV-19) has impacted human health on a global scale, while the interaction between the virus and the host is the foundation of the disease. The viral genome codes a cluster of proteins, each with a unique function in the event of host invasion or viral development. Under the current adverse situation, we employ virtual screening tools in searching for drugs and natural products which have been already deposited in DrugBank in an attempt to accelerate the drug discovery process. This study provides an initial evaluation of current drug candidates from various reports using our systemic in silico drug screening based on structures of viral proteins and human ACE2 receptor. Additionally, we have built an interactive online platform ( ) for browsing these results with the visual display of a small molecule docked on its potential target protein, without installing any specialized structural software. With continuous maintenance and incorporation of data from laboratory work, it may serve not only as the assessment tool for the new drug discovery but also an educational web site for the public.

<p>The emergence of the new coronavirus (nCoV-19) has brought global impact on human health, whilst the interaction between the virus and the host is the foundation of the disease. The viral genome codes a cluster of proteins, each with a unique function in the event of host invasion or viral development. Under current adverse situation, we employ virtual screening tools in searching for drugs and nature products which have been already deposited in the DrugBank in attempt to accelerate the drug discovery process. This study provides an initial evaluation of current drug candidates from various reports using our systemic in silico drug screening based on structures of viral proteins and human ACE2 receptor. Besides, we built an interactive online platform (<a href="https://shennongproject.com:11443/#/home">https://shennongproject.com:11443/#/home</a>) for browsing these results with the visual display of small molecule docked on its potential target protein, without installing any specialized structural software. With continuous maintenance and incorporation of data from laboratory works, it may serve not only as the assessment tool for the new drug discovery but also an educational website to meet general interest from the public.</p>

Phosphoinositide 3-kinase (PI3K) is an attractive target to potentially treat a range of disease states as illustrated by more than 15 inhibitors now in clinical trials.We disclose herein the discovery of a new class of fluoroquinolone derivatives having improved potency toward PI3K.The activity of the compound A3 as an inhibitor of PI3K was further investigated in human tumors cells. Notably, the compound A3 with potent inhibitory activity was low toxic. By compoutational docking studies, it was predicted that, like CAL-101, a known small-inhibitor of PI3K, compound A3 was tightly embedded into the ATP binding pocket with H bonds and π-cation interactions. Keywords Fluoroquinolone derivativesComputational docking PI3K inhibitor Antitumor activity.

INTRODUCTIONHepatocellular carcinoma (HCC) is the fifth most common solid tumor worldwide, accounting for 500 000 new cases annually. The majority of patients presenting with advanced disease are not candidates for liver transplantation, surgical resection, or regional therapy. In 60% to 80% of patients with HCC, underlying liver cirrhosis and hepatic dysfunction complicate its treatment. Systemic treatments have minimal effects with significant toxicity, and cannot improve patient survival [1] . The search for alternative treatment modalities has revived the concept of using oncolytic viruses to treat cancer [2,3] . In this respect, conditional replicative adenoviruses (CRAds) appear to be attractive anticancer agents that are currently evaluated in clinical trials [4,5] . CRAds exert intrinsic anticancer activity through selective replication and lysis in cancer cells. In addition, release of CRAd progeny by infected tumor cells provides a potential to amplify the oncolytic effect by lateral spread through solid tumors.Recent studies have shown that telomerase activity may serve as a general marker of cancer cells. Its activity in normal cells is restricted to fetal tissue, whereas it is elevated in tumors [6] . Although some tumors could activate a yet unknown alternative mechanism of telomere extension, the majority (> 85%) of human HCC cells acquire immortality by expressing telomerase reverse transcriptase (hTERT) [7] . It has been shown that hTERT expression is regulated at the transcriptional level, thereby providing a promising tool for tumor-specific gene expression.Hypoxia occurs in virtually allsolid tumors as they outgrow their blood supply. Hypoxia augments cellular levels of hypoxia-inducible factor (HIF), a transcription Abstract AIM: To develop a conditionally replicative gene-viral vector system called CNHK500-p53, which contains dual promoters within the E1 region, and combines the advantages of oncolytic virus and gene therapies for hepatocellular carcinoma (HCC).

Coxsackie B3 virus (CVB3) is a member of small RNA viruses that belongs to the genus Enterovirus of the family Picornaviridae and CVB3 is the main pathogen of acute and chronic viral myocarditis. In this study RT-qPCR was used to determine the expression of miR-107 in CVB3-infected and uninfected HeLa cells. The experimental results show that the level of miR-107 began to rise at 4 h after the infection, and significantly boosted at 6 h. Based on the results of this experiment, we consider that miR-107 expression is related to CVB3 infection. In order to further clarify the effect of miR-107 in the process of CVB3 infection, we studied the effect of miR-107 upstream and downstream target genes on CVB3 replication. Levels of the target RNAs were detected by RT-qPCR after CVB3 infection, and the expression of CVB3 capsid protein VP1 by western blot analysis. Then the virus in the supernatant was quantitated via a viral plaque assay, reflecting the release of the virus. The experimental results showed that miRNA-107 expression is associated with CVB3 replication and proliferation, while KLF4 and BACE1 as the downstream of miR-107 weakened CVB3 replication. Overexpressions of KLF4 and BACE1 negatively regulated CVB3 replication, this effect on CVB3 was completely opposite to that of miR-107. Further experiments revealed that the upstream lncRNA004787, a new lncRNA that had not been reported, was located on chromosome 5, strand - from 37073250 to 37070908 (genome assembly: hg19). We sequenced and studied lncRNA004787 and found that it partially inhibited CVB3 replication. This prompted us to speculate that lncRNA004787 probably impacted the replication by other means. In conclusion, miR-107 interfered with CVB3 replication and release.