The SARS-CoV-2 outbreak, began in late 2019, has caused a worldwide pandemic and shows no signs of slowing. Glucocorticoids (GCs), including dexamethasone (DEX), have been widely used as effective anti-inflammatory and immunosuppressant drugs. In this study, seven GCs had no obvious effect on cell viability of angiotensin converting enzyme 2 (ACE2) high expressed HEK293T cells when concentrations were under 10 μM. Molecular docking results revealed that DEX occupied with active binding site of ACE2 of SARS-CoV-2 spike protein. Surface plasmon resonance (SPR) results showed that K D value between DEX and ACE2 was (9.03 ± 0.78) e−6 M. Cell membrane chromatography (CMC) results uncovered that DEX had a chromatographic retention. DEX was found out to inhibiting the viropexis into ACE2 h cells using SARS-CoV-2 spike pseudotyped virus. Therefore, DEX inhibits the entrance of SARS-CoV-2 spike pseudotyped virus into cell by binding to ACE2.

Licochalcone A (Lico A) is a natural flavonoid belonging to the class of substituted chalcone that has various biological effects. Mast cells (MCs) are innate immune cells that mediate hypersensitivity and pseudo-allergic reactions. MAS-related GPR family member X2 (MRGPRX2) on MCs has been recognized as the main receptor for pseudo-allergic reactions. In this study, we investigated the anti-pseudo-allergy effect of Lico A and its underlying mechanism. Substance P (SP), as an MC activator, was used to establish an in vitro and in vivo model of pseudo-allergy. The in vivo effect of Lico A was investigated using passive cutaneous anaphylaxis (PCA) and active systemic allergy, along with degranulation, Ca 2+ influx in vitro. SP-induced laboratory of allergic disease 2 (LAD2) cell mRNA expression was explored using RNA-seq, and Lico A inhibited LAD2 cell activation by reverse transcription polymerase chain reaction (RT-PCR), western blotting, and immunofluorescence staining. Lico A showed an inhibitory effect on SP-induced MC activation and pseudo-allergy both in vitro and in vivo. The nuclear factor (NF)-κB pathway is involved in MRGPRX2 induced MC activation, which is inhibited by Lico A. In conclusion, Lico A inhibited the pseudoallergic reaction mediated by MRGPRX2 by blocking NF-κB nuclear migration.

The outbreak of coronavirus disease 2019 (COVID‐19) has induced a large number of deaths worldwide. Angiotensin‐converting enzyme 2 (ACE2) is the entry receptor for the 2019 novel coronavirus (2019‐nCoV) to infect the host cells. Therefore, ACE2 may be an important target for the prevention and treatment of COVID‐19. The aim of this study was to investigate the inhibition effect of valaciclovir hydrochloride (VACV), zidovudine (ZDV), saquinavir (SQV), and efavirenz (EFV) on 2019‐nCoV infection. The results of molecule docking and surface plasmon resonance showed that VACV, ZDV, SQV, and EFV could bind to ACE2 protein, with the K D value of (4.33 ± 0.09) e −8 , (6.29 ± 1.12) e −6 , (2.37 ± 0.59) e −5 , and (4.85 ± 1.57) e −5 M, respectively. But only ZDV and EFV prevent the 2019‐nCoV spike pseudotyped virus to enter ACE2‐HEK293T cells with an EC 50 value of 4.30 ± 1.46 and 3.92 ± 1.36 μM, respectively. ZDV and EFV also have a synergistic effect on preventing entry of virus into cells. In conclusion, ZDV and EFV suppress 2019‐nCoV infection of ACE2‐HEK293T cells by interacting with ACE2.

Chrysin, one of the most pharmacologically active natural flavonoids, has been extracted from various plants. Mast cells are an important part of innate immunity-mediating anaphylaxis. Pseudo-allergic reactions are currently believed to be associated with the MAS-related GPR family member X2 (MrgX2). In this study, the anti-pseudo allergy effect of chrysin and its underlying mechanisms were studied in vitro and in vivo. Chrysin inhibited passive cutaneous anaphylaxis and systemic pseudo-allergy in vivo. LAD2 cell degranulation, calcium ion (Ca2+) influx, and adenosine 5′-triphosphate (ATP) content were significantly suppressed in a dose-dependent manner. Chrysin suppressed pseudo-allergic reactions through the PLC/IP3/Ca2+ and ERK/STAT3 serine 727 pathways downstream of MrgX2. Therefore, mitochondrial ATP, but not glycolysis, is vital for pseudo-allergic reactions mediated by MrgX2. This study provides new insights for the treatment of pseudo-allergy.

Asthma is a heterogeneous disease related to numerous inflammatory cells, among which mast cells play an important role in the early stages of asthma. Therefore, treatment of asthma targeting mast cells is of great research value. α‐Asarone is an important anti‐inflammatory component of the traditional Chinese medicine Acorus calamus L, which has a variety of medicinal values. To investigate whether α‐asarone can alleviate asthma symptoms and its mechanism. In this study, we investigated the effect of α‐asarone on mast cell activation in vivo and in vitro. The release of chemokines or cytokines, AHR (airway hyperresponsiveness), and mast cell activation were examined in a mast cell‐dependent asthma model. Western blot was performed to determine the underlying pathway. α‐Asarone inhibited the degranulation of LAD2 (laboratory allergic disease 2) cells and decreased IL‐8, MCP‐1, histamine, and TNF‐α in vitro. α‐Asarone reduced paw swelling and leakage of Evans blue, as well as serum histamine, CCL2, and TNF‐α in vivo. In the asthma model, α‐asarone showed an inhibitory effect on AHR, inflammation, mast cells activation, infiltration of inflammatory cells, and the release of IL‐5 and IL‐13 in lung tissue. α‐Asarone decreased the levels of phosphorylated JAK2, phosphorylated ERK, and phosphorylated STAT3 induced by C48/80. Our findings suggest that α‐asarone alleviates allergic asthma by inhibiting mast cell activation through the ERK/JAK2‐STAT3 pathway.