Peptide T is an octapeptide from the V2 region of HIV-1 gp120. Peptide T is a ligand for the CD4 receptor and prevents binding of HIV to the CD4 receptor.
HIV-1 inhibitor-35 (compound 74) is a potent HIV-1 inhibitor with EC50s of 80 nM and 70 nM for LTR and CMV in HEK293 cells, respectively. HIV-1 inhibitor-35 has inhibitory activity against liver cancer cell HepG2 with a CC50 of 40 nM. HIV-1 inhibitor-35 can be used as HIV-1 latency reversing agent[1].
Soyasaponin II is a saponin with antiviral activity. Soyasaponin II inhibits the replication of HSV-1, HCMV, influenza virus, and HIV-1. Soyasaponin II shows potent inhibition on HSV-1 replication. Soyasaponin II serves as a inhibitor for YB-1 phosphorylation and NLRP3 inflammasome priming and could protect mice against LPS/GalN induced acute liver failure[1][2].
SJ-3366 (IQP-0410) is a potent inhibitor of HIV nonnucleoside reverse transcriptase[1]. SJ-3366 (IQP-0410) inhibits HIV at sub-nanomolar concentrations primarily through a typical non-nucleoside mechanism[2].
Valopicitabine (NM283), an efficient prodrug of the potent anti-HCV agent 2'-C-methylcytidine, acts as a promising antiviral agent for reasearch of chronic HCV infection[1].
Methyl salvionolate A is a potent inhibitor of HIV-1. Methyl salvionolate A inhibits P24 antigen in HIV-1 infected MT-4 cell with an EC50 of 1.62 μg/ml. Methyl salvionolate A also inhibits HIV-1 reverse transcriptase, protease and integrase with IC50s of 50.58, 10.73 and 7.58 μg/ml, respectively[1].
(2RS)-FPMPA can be used for synthesis of antiretroviral agents against HIV-1 and HIV-2[1].
Novel capsid targeted inhibitor of HIV-1 replication
5-Fluorouracil-13C4,15N2 is the 13C and 15N labeled 5-Fluorouracil[1]. 5-Fluorouracil (5-FU) is an analogue of uracil and a potent antitumor agent. 5-Fluorouracil affects pyrimidine synthesis by inhibiting thymidylate synthetase thus depleting intracellular dTTP pools. 5-Fluorouracil induces apoptosis and can be used as a chemical sensitizer[2][3]. 5-Fluorouracil also inhibits HIV[4].
RPR103611, the betulinic acid derivative, is a potent HIV-1 entry inhibitor with IC50s of 80, 0.27, and 0.17 for CCR5-tropic virus YU2, CXCR4-tropic virus NL4-3 and dual tropic virus 89.6, respectively[1].
ZINC04177596 is a potent HIV-negative factor (HIV-Nef) protein inhibitor. Nef is an accessory gene product of HIV and has an imperative role in viral replication and AIDS pathogenesis[1].
HIV-1 inhibitor-27 (compound 5) is a potent HIV-1 inhibitor with IC50s of 16 μM, 0.5 μM and 0.39 μM for HIV-1 YU2, NL4-3 and 89.6 strain, respectively. HIV-1 inhibitor-27 has low cytotoxicity with a CC50 of 128 μM in TZM-bl cells. HIV-1 inhibitor-27 can be used for researching AIDS[1].
HIV-1 inhibitor-57 (Compound 12g) is a HIV inhibitor. HIV-1 inhibitor-57 is active against wild-type and five prevalent NNRTI-resistant HIV-1 strains with EC50 values ranging from 0.024 to 0.0010 μM. HIV-1 inhibitor-57 forms additional interactions with residues around the binding site in HIV-1 RT[1].
Claficapavir (A1752) is a specific nucleocapsid protein (NC) inhibitor with an IC50 around 1 μM. Claficapavir strongly binds the HIV-1 NC (Kd=20 nM) thereby inhibiting the chaperone properties of NC and leading to good antiviral activity against the HIV-1[1].
VEC-5 is a HIV-1 inhibitor. VEC5 have been evaluated for their inhibitory potential employing ligand receptor and protein-protein interactions studies. VEC-5 exhibited better interaction with Vif than RN18.
Saquinavir(Ro 31-8959) is an HIV Protease inhibitor used in antiretroviral therapy. IC50 Value: Target: HIV ProteaseSaquinavir is a protease inhibitor. Proteases are enzymes that cleave protein molecules into smaller fragments. HIV protease is vital for both viral replication within the cell and release of mature viral particles from an infected cell. Saquinavir binds to the active site of the viral protease and prevents cleavage of viral polyproteins, preventing maturation of the virus. Saquinavir inhibits both HIV-1 and HIV-2 proteases.Studies have also looked at Saquinavir as a possible anti-cancer agent.
AL-470 is a potent antiviral agent with EC50 values of 0.27, 0.63, and 0.35 µM against HIV-1, HIV-2, and EV-A71, respectively[1].
Teicoplanin sodium (Antibiotic MDL-507 sodium) is a potent lipoglycopeptide antibiotic. Teicoplanin sodium shows antiviral activity for HIV-1, SARS-CoV1 and SARS-CoV2. Teicoplanin sodium shows anti-MRSA activity[1][2].
BMS-538203 is a highly efficient HIV integrase inhibitor and antiviral agent.IC50 value:Target: HIV integraseIn the current study we demonstrate a hit-to-clinical candidate pathway that resulted in 50- and 2000-fold improvements in enzyme-inhibition and antiviral activity without an increase in molecular weight or change in molecular topology. The original hit , 1 (mw = 268) was optimized in a stepwise manner. Potential covalent protein-binding moieties were removed by reducing the number of the ketone groups. High enzyme inhibition activity was achieved by optimizing the aryl-portion of the molecule. Protein binding was reduced by replacing the standard amide by the corresponding methyl-hydroxamide. This eventually led to the discovery of BMS-538203 compound 2 (mw = 269) a highly efficient inhibitor and antiviral agent.
Atazanavir sulfate is a sulfate salt form of atazanavir that is an highly potent HIV-1 protease inhibitor.Target: HIV-1 protease inhibitorAtazanavir sulfate is a sulfate salt form of atazanavir that is an highly potent HIV-1 protease inhibitor. It has a pharmacokinetic profile that supports once-daily dosing and has demonstrated a unique resistance profile and superior virologic potency compared with other antiretrovirals in vitro. In subjects with HIV, atazanavir (400 mg once daily) produced rapid and sustained improvements in viral load and CD4 counts in both antiretroviral-naive as well as previously treated patients when used in combination with dual nucleoside reverse transcriptase inhibitor (NRTI) treatment [1].After intravenous (iv), oral (po) and intraportal (ip) administration of ATV at a dosage of 7 mg/kg, AUCs in HL rats were 12.41, 5.24 and 8.89 microg/mLh, respectively, and were significantly higher than those in control rats (4.09, 1.70 and 3.38 microg/mLh). Despite the decrease of distribution volume (Vd(ss)), the terminal half-life (t(1/2)) in HL tended to be shorter than in control, and hepatic distribution of ATV in HL rats was 4.8-fold increases. These results suggested that the uptake of ATV into liver might counteract the decrease of Vd(ss). On the other hand, there was no significant difference in bioavailability, and the lymphatic transport to AUC showed no statistical change. In conclusion, although the protein binding rate and AUC were significantly increased, the pharmacokinetics of ATV might be tolerated in HL [2].Clinical indications: HIV-1 infection Toxicity: torsades de pointes
HIV-IN-1 (Compound 50) is a potent inhibitor of HIV. HIV-IN-2 has the potential for the research of HIV infection[1].
HEP-1 (Human ezrin peptide (324-337)) is an orally active peptide with anti-HIV activity. HEP-1 enhances antibody titers generated by hepatitis B vaccination. HEP-1 has the potential to be studied against viral infections[1].
RN-18 is a HIV-1 viral infectivity factor (HIV-1 Vif) inhibitor with an IC50 of 6 μM in nonpermissive H9 cells.
Tenofovir dsoproxil is a nucleotide reverse transcriptase inhibitor to treat HIV and chronic Hepatitis B.
Kadsuralignan A (compound 1) is a dibenzocyclooctadiene lignan isolated from the leaves and stems of Schisandra lancifolia. Kadsuralignan A has anti-HIV activity with EC50=2.23 μg/mL[1].
Rilpivirine (R278474; TMC278) is a type of anti-HIV medicine called a non-nucleoside reverse transcriptase inhibitor (NNRTI).
Amprenavir (Agenerase) is a HIV protease inhibitor(Ki=0.6 nM) used to treat HIV infection.IC50 Value: 0.6 nM (Ki); Against wild-type clinical HIV isolates:14.6 +/- 12.5 ng/mL (mean +/- SD) [1].Target: HIV proteasein vitro: Amprenavir has an enzyme inhibition constant (Ki = 0.6 nM) that falls within the Ki range of the other protease inhibitors. Amprenavir's in vitro 50% inhibitory concentration (IC50) against wild-type clinical HIV isolates is 14.6 +/- 12.5 ng/mL (mean +/- SD) [1]. Amprenavir had direct inhibitory effects on invasion of Huh-7 hepatocarcinoma cell lines, inhibiting MMP proteolytic activation [2].in vivo: Amprenavir was able to promote regression of hepatocarcinoma growth in vivo by anti-angiogenetic and overall anti-tumor activities, independently by PI3K/AKT related pathways that at today is one of the more suggestive hypothesis to explain the anti-tumor effects of the different protease inhibitors [2]. Amprenavir efficiently activated PXR and induced PXR target gene expression in vitro and in vivo. Short-term exposure to amprenavirsignificantly increased plasma total cholesterol and atherogenic low-density lipoprotein cholesterol levels in wild-type mice, but not in PXR-deficient mice [3]. Amprenavir has been approved for adults and children; the recommended capsule doses are 1200 mg twice daily for adults and 20 mg/kg twice daily or 15 mg/kg 3 times daily for children < 13 years of age or adolescents < 50 kg [1].Clinical trial: A Study to Compare Three Doses of T-20 When Given in Combination With Abacavir, Amprenavir, Ritonavir, and Efavirenz to HIV-Infected Adults. Phase 2
3′-Azido-2′,3′-dideoxyuridine (AzdU) is a nucleoside analog of Zidovudine (HY-17413). 3′-Azido-2′,3′-dideoxyuridine is a potent inhibitor of human immunodeficiency virus (HIV) replication in human peripheral blood mononuclear cells (PBMC) with limited toxicity for human bone marrow cells (BMC)[1][2][3].
Kadsuracoccinic acid A is a tetracyclic natural compound that can be isolated from the stems of Kadsura coccinea. Kadsuracoccinic acid A has vitro anti-HIV-1 activitiy with an EC50 value of 68.7 μM[1].
Azvudine is a potent nucleoside reverse transcriptase inhibitor (NRTI), with antiviral activity on HIV, HBV and HCV. Azvudine exerts highly potent inhibition on HIV-1 (EC50s ranging from 0.03 to 6.92 nM) and HIV-2 (EC50s ranging from 0.018 to 0.025 nM). Azvudine inhibits NRTI-resistant viral strains[1].