In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

Input: Consider Input: The global spread of SARS-CoV-2 requires an urgent need to find effective therapeutics for the treatment of COVID-19. We developed a data-driven drug repositioning framework, which applies both machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. The retrospective study using the past SARS-CoV and MERS-CoV data demonstrated that our machine learning based method can successfully predict effective drug candidates : bioRxiv preprint against a specific coronavirus. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 is able to suppress the CpG-induced IL-6 production in peripheral blood mononuclear cells, suggesting that it may also have anti-inflammatory effect that is highly relevant to the prevention immunopathology induced by SARS-CoV-2 infection. Further pharmacokinetic and toxicokinetic evaluation in rats and monkeys showed a high concentration of CVL218 in lung and observed no apparent signs of toxicity, indicating the appealing potential of this drug for the treatment of the pneumonia caused by SARS-CoV-2 infection. Moreover, molecular docking simulation suggested that CVL218 may bind to the N-terminal domain of nucleocapsid (N) protein of SARS-CoV-2, providing a possible model to explain its antiviral action. We also proposed several possible mechanisms to explain the antiviral activities of PARP1 inhibitors against SARS-CoV-2, based on the data present in this study and previous evidences reported in the literature. In summary, the PARP1 inhibitor CVL218 discovered by our data-driven drug repositioning framework can serve as a potential therapeutic agent for the treatment of COVID-19. author/funder. All rights reserved. No reuse allowed without permission. : bioRxiv preprint known evidences reported in the literature, we also discussed several putative mechanisms of the anti-SARS-CoV-2 effects for CVL218 or other PARP1 inhibitors to be involved in the treatment of COVID-19. Overall, our results indicated that the PARP1 inhibitor CVL218 identified by our drug repositioning pipeline may serve as an effective therapeutic agent against COVID-19. Results The overview of our data-driven drug repositioning framework is shown in Figure 1A . We first constructed a virus related knowledge graph consisting of drug-target interactions, protein-protein interactions and similarity networks from publically available databases (Methods). Three different types of nodes (i.e., drugs, human targets and virus targets) within the knowledge graph were connected through edges describing their interactions, associations or similarities to establish bridges of information aggregation and knowledge mining. We then applied a network-based knowledge mining algorithm to predict an initial list of drug candidates that can be potentially used to treat SARS-CoV-2 infection ( Figure 1B and Methods). Next, we further narrowed down the list of drug candidates with the previously reported evidences of antiviral activities based on the text mining results from the large-scale literature texts, which were derived through a deep learning based relation extraction method named BERE [4] ( Figure 1C and Methods), followed by a minimum of manual checking. After that, we used the connectivity map analysis approach [5] with the gene expression profiles of ten SARS-CoV-infected patients [6] to further refine the list of drug candidates against SARS-CoV-2 ( Figure 1D , Table 1, Table S1 and Methods). The above screening process revealed that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor PJ-34 could potentially have the antiviral activities against SARS-CoV-2. 4 author/funder. All rights reserved. No reuse allowed without permission.

Output: A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19


Input: Consider Input: Aptamers are short, single-stranded DNA, RNA, or synthetic XNA molecules that can be developed with high affinity and specificity to interact with any desired targets. They have been widely used in facilitating discoveries in basic research, ensuring food safety and monitoring the environment. Furthermore, aptamers play promising roles as clinical diagnostics and therapeutic agents. This review provides update on the recent advances in this rapidly progressing field of research with particular emphasis on generation of aptamers and their applications in biosensing, biotechnology and medicine. The limitations and future directions of aptamers in target specific delivery and real-time detection are also discussed.

Output: molecules Recent Advances in Aptamer Discovery and Applications


Input: Consider Input: Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.


Output: Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay