Emerging coronaviruses (CoVs) primarily cause severe gastroenteric or respiratory diseases in humans and animals, and no approved therapeutics are currently available. Here, A9, a receptor tyrosine kinase inhibitor (RTKI) of the tyrphostin class, is identified as a robust inhibitor of transmissible gastroenteritis virus (TGEV) infection in cell-based assays. Moreover, A9 exhibited potent antiviral activity against the replication of various CoVs, including murine hepatitis virus (MHV), porcine epidemic diarrhea virus (PEDV) and feline infectious peritonitis virus (FIPV). We further performed a comparative phosphoproteomic analysis to investigate the mechanism of action of A9 against TGEV infection in vitro. We specifically identified p38 and JNK1, which are the downstream molecules of receptor tyrosine kinases (RTKs) required for efficient TGEV replication, as A9 targets through plaque assays, qRT-PCR and Western blotting assays. p38 and JNK1 inhibitors and RNA interference further showed that the inhibitory activity of A9 against TGEV infection was mainly mediated by the p38 mitogen-activated protein kinase (MAPK) signaling pathway. All these findings indicated that the RTKI A9 directly inhibits TGEV replication and that its inhibitory activity against TGEV replication mainly occurs by targeting p38, which provides vital clues to the design of novel drugs against CoVs.

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Them onofluoroalkenes ubstructure shows ah igh potentiala saf luorinated synthon in organic synthesis. However, control of the Z/E stereoselectivity of multi-substituted monofluoroalkenep roducts in one-pot reactions still remains ac hallenge. An unprecedented one-pot approach for the highly regio-ands tereoselective preparation of functionalized (Z)-b-monofluoro tri-substituted alkenes from readily available b-chloro-a,b-unsaturated aldehydes or ketones has been explored. Mechanistic studies demonstrated that the reactioni si nitiated by dehy-drochlorination of the substrates to give alkynyl aldehydes/ketones,f ollowed by their trans-hydrofluorination. It is worth mentioning that af luorinating reagent with suitable basicity andn ucleophilicity plays ak ey role in promoting the formationo f( Z)-bfluoro-b-aryl tri-substituted monofluoroalkenes.

In this work, we report a novel phosphorus element heterostructure with snowflake-like morphology consisting of 1D rod black phosphorus (BP) and 2D flake red phosphorus (RP). The content of black...

Among the research fields of the internet of things (IOT), business model is the key point to apply the high technology into real life. In this paper, e 3 -value methodology is applied to clarify the business model for a typical application of IOT-drug supply chain. The designed models show up the exchanges of value objects between specific actors in the industry chain of IOT. Keywordsinternet of things business model drug supply chain e 3 -value