Teacher: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.
Teacher: Now, understand the problem? Solve this instance: Bunyaviruses are significant human pathogens, causing diseases ranging from hemorrhagic 26 fevers to encephalitis. Among these viruses, La Crosse virus (LACV), a member of the California 27 serogroup, circulates in the eastern and midwestern United States. While LACV infection is often 28 asymptomatic, dozens of cases of encephalitis are reported yearly. Unfortunately, no antivirals 29 have been approved to treat LACV infection. Here, we developed a method to rapidly test potential 30 antivirals against LACV infection. From this screen, we identified several potential antiviral 31 molecules, including known antivirals. Additionally, we identified many novel antivirals that 32 exhibited antiviral activity without affecting cellular viability. Valinomycin, a potassium ionophore, 33 was among our top targets. We found that valinomycin exhibited potent anti-LACV activity in 34 multiple cell types in a dose-dependent manner. Valinomycin did not affect particle stability or 35 infectivity, suggesting that it may preclude virus replication by altering cellular potassium ions, a 36 known determinant of LACV entry. We extended these results to other ionophores and found that 37 the antiviral activity of valinomycin extended to other viral families including bunyaviruses (Rift 38 Valley fever virus, Keystone virus), enteroviruses (Coxsackievirus, rhinovirus), flavirivuses (Zika), 39 and coronaviruses (229E and MERS-CoV). In all viral infections, we observed significant 40 reductions in virus titer in valinomycin-treated cells. In sum, we demonstrate the importance of 41 potassium ions to virus infection, suggesting a potential therapeutic target to disrupt virus 42 replication. 43 44 Importance 45 No antivirals are approved for the treatment of bunyavirus infection. The ability to rapidly screen 46 compounds and identify novel antivirals is one means to accelerate drug discovery for viruses 47 with no approved treatments. We used this approach to screen hundreds of compounds against 48 La Crosse virus, an emerging bunyavirus that causes significant disease, including encephalitis. 49 We identified several known and previously unidentified antivirals. We focused on a potassium 50 ionophore, valinomycin, due to its promising in vitro antiviral activity. We demonstrate that 51 valinomycin, as well as a selection of other ionophores, exhibits activity against La Crosse virus 52 as well as several other distantly related bunyaviruses. We finally observe that valinomycin has 53 activity against a wide array of human viral pathogens, suggesting that disrupting potassium ion 54 homeostasis with valinomycin may be a potent host pathway to target to quell virus infection.
Student:
Novel ionophores active against La Crosse virus identified through rapid 1 antiviral screening 2 3