Flavivirus Infection

Cephaeline ((-)-Cephaeline; NSC 32944) is a ferroptosis inducer, with broad-spectrum anticancer and antiviral activities. Cephaeline induces ferroptosis (Ferroptosis) by upregulating p53, inhibiting NRF2, activating ULK3, downregulating the expressions of SLC7A11 and GPX4 in a p53-dependent manner, reducing GSH and mitochondrial membrane potential, and increasing lipid peroxidation and iron accumulation. Cephaeline inhibits cancer cell proliferation, migration and tumor growth. Cephaeline inhibits Ebola virus (EBOV) VLP entry and infection, with IC₅₀ values of 3.27 μM and 22.18 μM respectively; it also inhibits Zika virus (ZIKV) NS5 RdRp activity (IC₅₀ = 976 nM), and binds to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RdRp and N protein, with K_d values of 8.9 μM and 53.8 μM respectively. Cephaeline can be used in studies related to breast cancer, lung cancer, COVID-19, EBOV and ZIKV infections.

Maackiain (DL-Maackiain) is an orally active multi-target inhibitor with anti-tumor activity and neuroprotective effects. Maackiain activates the AMPK, NLRP3 and Nrf2/HO-1 pathways, and inhibits key targets such as NF-κB, mTOR, MAO-B, NFATc1 and PKCδ, thereby precisely regulating processes including apoptosis, autophagy and pyroptosis. Maackiain also effectively inhibits microglial activation, osteoclast formation, and proliferation and invasion of tumor cells, and protects dopaminergic neurons from damage. Maackiain is applicable to the research of various diseases such as Alzheimer's disease, osteoporosis, sepsis and dengue fever。

Aminomethyltrioxsalen hydrochloride is a psoralen derivative. Aminomethyltrioxsalen hydrochloride can penetrate intact cells and react with nucleic acid secondary structures in vivo without disrupting the tissue structure of natural nucleoproteins. Aminomethyltrioxsalen hydrochloride inactivates viruses by crosslinking nucleic acid pyrimidine residues after exposure to UV-A radiation. Aminomethyltrioxsalen hydrochloride can be used in research related to dengue virus infection.

Demethylasterriquinone B1 (DAQ B1; L-783281) is an orally active insulin receptor (insulin receptor) agonist and AKT activator. By activating AKT, Demethylasterriquinone B1 upregulates the expression and activity of eNOS to increase NO production, while downregulating the expression of the NADPH oxidase subunit p22phox to reduce oxidative stress and improve vascular endothelial dysfunction in hypertensive rats. Demethylasterriquinone B1 combind with an AKT inhibitor targets the insulin signaling pathway to activate two antiviral pathways, RNA interference and JAK/STAT, in mosquitoes, thereby reducing Zika virus infection.

Azaleatin is an orally active inhibitor of hQC, NS2B-NS3 protease and E. coli β-glucuronidase, with IC₅₀ values of 1.1 μM, 38.00 μg/mL and 0.57 μM, respectively. Azaleatin inhibits the activities of NF-κB, MyD88, JAK1, TLR4, STAT3, IL-1β, IL-6, COX-2, TNF-α and β-glucuronidase, blocks pro-inflammatory signaling pathways, reduces the levels of ROS, MDA and uric acid, elevates the levels of GPx, GSR, GST, SOD, CAT, HO-1 and GSH, scavenges free radicals and exerts reducing capacity. Azaleatin inhibits the expression of pro-apoptotic proteins Bax, Caspase-9 and Caspase-3, and upregulates the expression of anti-apoptotic protein Bcl-2. Azaleatin reduces the levels of cardiac injury markers, restores cardiac histological structure, inhibits Aβ aggregation, dengue protease activity, hepatic stellate cell proliferation and cancer cell growth, and also exhibits antibacterial activity. Azaleatin can be used in studies related to subchronic cardiotoxicity, Alzheimer's disease, dengue fever, hyperuricemia, liver fibrosis, gastric cancer and bacterial infections.

Cephaeline dihydrobromide ((-)-Cephaeline (dihydrobromide); NSC 32944 (dihydrobromide)) is a ferroptosis inducer, with broad-spectrum anticancer and antiviral activities. Cephaeline dihydrobromide induces ferroptosis (Ferroptosis) by upregulating p53, inhibiting NRF2, activating ULK3, downregulating the expressions of SLC7A11 and GPX4 in a p53-dependent manner, reducing GSH and mitochondrial membrane potential, and increasing lipid peroxidation and iron accumulation. Cephaeline dihydrobromide inhibits cancer cell proliferation, migration and tumor growth. Cephaeline dihydrobromide inhibits Ebola virus (EBOV) VLP entry and infection, with IC₅₀ values of 3.27 μM and 22.18 μM respectively; it also inhibits Zika virus (ZIKV) NS5 RdRp activity (IC₅₀ = 976 nM), and binds to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RdRp and N protein, with K_d values of 8.9 μM and 53.8 μM respectively. Cephaeline dihydrobromide can be used in studies related to breast cancer, lung cancer, COVID-19, EBOV and ZIKV infections.

Cephaeline hydrochloride ((-)-Cephaeline (hydrochloride); NSC 32944 (monohydrochloride)) is a ferroptosis inducer, with broad-spectrum anticancer and antiviral activities. Cephaeline hydrochloride induces Ferroptosis by upregulating p53, inhibiting NRF2, activating ULK3, downregulating the expressions of SLC7A11 and GPX4 in a p53-dependent manner, reducing GSH and mitochondrial membrane potential, and increasing lipid peroxidation and iron accumulation. Cephaeline hydrochloride inhibits cancer cell proliferation, migration and tumor growth. Cephaeline hydrochloride inhibits Ebola virus (EBOV) VLP entry and infection, with IC₅₀ values of 3.27 μM and 22.18 μM respectively; it also inhibits Zika virus (ZIKV) NS5 RdRp activity (IC₅₀ = 976 nM), and binds to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RdRp and N protein, with K_d values of 8.9 μM and 53.8 μM respectively. Cephaeline hydrochloride can be used in studies related to breast cancer, lung cancer, COVID-19, EBOV and ZIKV infections.

SP-393D is an amidoxime-based prodrug inhibitor targeting dengue virus NS2B/NS3. The EC₅₀ values of SP-393D in Huh7 cells infected with DENV-1, DENV-2, DENV-3 and DENV-4 are 1.41, 0.066, 0.66 and 0.071 μM, respectively, while its CC₅₀ against Huh7 cells is >100 μM. SP-393D exhibits pan-serotypic activity against dengue virus serotypes 1, 2, 3 and 4. SP-393D binds to the allosteric pocket of dengue virus NS2B/NS3 protease and generates additional hydrogen bonding interactions. SP-393D can be used in studies related to dengue virus infection.

γ-Carboline is a skeleton and antiviral agent. γ-Carboline shows anti-BVDV activity, with an EC₅₀  of  2.0  μM. γ-Carboline derivatives show anti-BVDV, antibacterial, antifungal, antitumor activity.

JMX0207 is an orally active flavivirus NS2B-NS3 protease inhibitor. JMX0207 showed an IC_50-SLC of 1.3 μM for blocking NS2B-NS3 protein interaction and an IC_50-pro of 8.2 μM for inhibiting protease catalytic activity.. JMX0207 directly binds viral NS3 protease at the NS2B-NS3 interface with a K_d of 1.1 μM, blocks viral polyprotein precursor processing, suppresses viral RNA replication and viral protein production. JMX0207 can be used for the study of Zika virus infection and Dengue virus infection.

ZIKV-IN-9 is a ZIKV inhibitor that blocks the early binding of viral particles to the cell surface. ZIKV-IN-9 inhibits ZIKV in various cell models. ZIKV-IN-9 is applicable to research related to Zika virus infection.

ToP-DNJ is a selective endoplasmic reticulum α-glucosidase II (GluII) inhibitor with an IC₅₀ value of 9.0 μM. ToP-DNJ selectively inhibits the two catalytic reactions of GluII, and exhibits stronger activity in the first step of converting di-glycosylated glycans to mono-glycosylated glycans. ToP-DNJ exhibits anti-DENV activity. ToP-DNJ can be used in studies related to dengue virus infection.

NITD-203 is a RdRp domain inhibitor. NITD 203 induces inhibition of the four DENV serotypes, as well as of YFV and WNV.

IRBM-Z-2 is a non-competitive, orally active Zika virus (ZIKV) NS2B-NS3 protease inhibitor, with IC₅₀ values of 0.04 μM and 3.1 μM against the wild-type and I156T mutant strains, respectively. IRBM-Z-2 exhibits broad-spectrum anti-flavivirus potential, with IC₅₀ values of 2.1 μM and 0.09 μM against the NS2B-NS3 proteases of dengue virus 2 (DENV2) and West Nile virus (WNV), respectively. IRBM-Z-1 inhibits ZIKV replication and alleviates virus-induced cytopathic effects. IRBM-Z-1 can be used in studies related to ZIKV infection.

CN-716 dihydrochloride is a reversible covalent flavivirus NS2B·NS3 protease inhibitor with antiviral activity. CN-716 dihydrochloride effectively inhibits the replication of dengue virus (DENV2), West Nile virus (WNV) and Zika virus (ZIKV). The IC₅₀ values of CN-716 dihydrochloride against the proteases of the above three viruses are 0.066 μM, 0.11 μM and 0.25 μM, respectively, while the K_i values against the same proteases are 0.051 μM, 0.082 μM and 0.04 μM, respectively. CN-716 dihydrochloride can be used to study the infection mechanisms of dengue fever, West Nile fever and Zika virus infection.

ZX-2401 (Compound 98a) is a 1,3,5-Triazine-based analogue of Purine (HY-34431). ZX-2401 has a significant antiviral activity against viruses of the Flaviviridae family, such as West Nile Virus (WNV), Hepatitis C (HCV), Yellow Fever Virus (YFV), Dengue Virus (DV), Bovine Viral Diarrhea Virus (BVDV) and Banzi Virus (BV) with EC₉₀s of 0.6-10 μg/mL. ZX-2401 significantly reduces virus production with an EC₉₀ of 3.3 mg/mL. ZX-2401 can be used for influenza infections research.