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.

of the virus per se and cellular NF-B activity; and (ii) to study the underling mechanisms. We found that tylophorine-based compounds target the TGEV viral RNA and effectively inhibit TGEV replication. NF-B inhibition also leads to anti-TGEV replication. NF-B activation induced by TGEV infection was found to be associated with two convergent pathways, IKK-2_IB/p65 and JAK2 mediated p65 phosphorylation, in swine testicular cells. JAK2 inhibition either by CYT387 (a JAK family inhibitor) or by silencing JAK2-expression revealed a dominant JAK2 mediated p65 phosphorylation pathway for NF-B activation and resulted in NF-B inhibition, which overrode the IB regulation via the IKK-2. Finally, tylophorine-based compounds work cooperatively with CYT387 to impart comprehensive anti-TGEV activities. The combination treatment, wherein a tylophorine compound targets TGEV and a JAK2 inhibitor blocks the alternative dominant NF-B activation mediated by JAK2, is more effective and comprehensive than either one alone and constitutes a feasible approach for the treatment of SARS-CoV or MERS-CoV. Coronaviruses are animal viruses containing an enveloped, positive-sense, single-stranded RNA genome; and include the common cold human coronavirus (CoV)-229E & CoV-OC43, severe acute respiratory syndrome (SARS) CoV, Middle East respiratory syndrome (MERS) CoV, porcine transmissible gastroenteritis virus (TGEV), and murine hepatitis virus (MHV) etc 1-3 . Since the 2003 SARS outbreak (which had a mortality rate of ~10%), novel anti-SARS-CoV treatments have been vigorously pursued. No new cases of SARS have been reported since the 2003 outbreak, but another novel coronavirus (MERS-CoV), this time with a mortality rate of ~35%, came to light in 2012 4 . To date, neither a commercially available vaccine for human coronaviruses nor a specific treatment for SARS-CoV or MERS-CoV is available. Coronaviruses primarily infect the upper respiratory and gastrointestinal tract and induce host inflammation 5 . Nuclear factor B (NF-B) activation by coronaviruses is usually responsible for mediating the production of pro-inflammatory cytokines and chemokines and thus plays an important role in the pathogenesis of disease caused by coronaviruses 6, 7 . Inhibition of NF-B-mediated inflammation induced by coronavirus in mice was reported to increase the survival rate 6 . Thus, NF-B inhibitors constitute a promising class of antivirals in infections caused by pathogenic coronaviruses. However, targeting NF-B is limited by intrinsic pathway complexity, cross talk with other pathways, and drug resistance 8 . In addition, many small chemical molecules targeting either viral entry or the intracellular viral life cycle were reported to impart anti-coronavirus activity 2, 9, 10 . Despite these advances, however, SARS-CoV and MERS-CoV remain untreatable diseases for which novel therapies are sought. Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 4105 | Tylophorine based compounds, whether isolated from plants, e.g. Asclepiadaceae and Moraceae or chemically synthesized, exert potent anti-coronaviral activities against a variety of coronaviruses including SARS-CoV, MHV, and TGEV 11, 12 , but both the underlying mechanism(s) of this inhibitory effect and the target are unknown. NF-B is significantly activated after infection by coronaviruses, e.g. TGEV, and MHV etc 6, 7, [13] [14] [15] . Otherwise, coronaviral nucleocapsid (N) protein plays a vital role in the regulation of viral genome replication and host gene transcription 16 . Therefore, the combination treatment for the inhibition of coronavirus per se, e.g. viral genome replication, and blocking cellular NF-B activation by coronaviruses, is a promising approach for the development of anti-coronavirals. TGEV infected swine testicular (ST) cells constitute a surrogate system for the search and study of potential anti-coronavirus agents 11, 12, 17 . Herein, we report: (1) tylophorine-based compounds exert potent anti-TGEV replication by directly targeting the viral RNA/ribonucleoprotein (RNP) complex for viral replication/synthesis; (2) NF-B inhibition also leads to anti-TGEV replication; (3) A combination treatment consisting of both a tylophorine compound and an NF-B inhibitor acts additively or synergically to more effectively and comprehensively inhibit TGEV replication than either (1) or (2) alone.
Targeting Coronaviral Replication and Cellular JAK2 Mediated Dominant NF-B Activation for Comprehensive and Ultimate Inhibition of Coronaviral Activity OPEN

Emerging and re-emerging pathogens and bioterror threats require an organized and coherent response from the worldwide research community to maximize available resources and competencies with the primary goals to understand the pathogen and enable intervention. In 2001, the Structural Proteomics In Europe project prototyped the pan-viral structural genomic approach, and the SARS outbreak in 2003 accelerated the concept of structural characterization of all proteins from a viral proteome and the interaction with their host partners. Following that approach, in 2004 the center for Functional and Structural Proteomics for SARS-CoV related proteins was initiated as part of the US NIH NIAID proteomics resource centers. Across worldwide efforts in Asia, Europe and America, the international research teams working on SARS-CoV have now determined experimental structural information for 45% of the SARS-CoV proteins and 53% of all its soluble proteins. This data is fully available to the scientific community and is providing an unprecedented level of insight to this class of RNA viruses. The efforts and results by the international scientific community to the SARS outbreak are serving as an example and roadmap of a rapid response using modern research methods.
International Research Networks in Viral Structural Proteomics: again, lessons from SARS

Despite a 60-year history of discovery, trial and evaluation of scores of different compounds, there are no currently licensed effective antivirals for the common cold. The history of the development and abandonment of all potential compounds so far teaches us some important lessons for the continuation of our fight against colds. First, the common cold is a benign self-limiting condition, making the consumption of 'harmless' antivirals a requisite of prime importance for regulators. Second, the common cold is a syndrome caused by a myriad of known and unknown agents, which reduces the effectiveness of compounds that interfere with single specific agents or types of agents. The multifactorial nature of the genesis of colds makes it difficult for compounds showing in vitro efficacy to 'make the jump' to field effectiveness. Last, despite the heavy burden that the cold imposes on society, the vagueness and shortness of symptoms make it difficult for sufferers to present in time for physicians to prescribe antivirals, which are only effective if taken within a short time frame. Attention should be paid to the development of compounds with a non-virus-specific action.
Antivirals for the common cold