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.
Epicoccone B, firstly reported from C. globosum, exhibits the DPPH free radical scavenging ability with IC50 value of 10.8 μM, and has potent α-glucosidase inhibition with IC50 value of 27.3 μM. Anti-HIV activity[1][2].
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].
Melliferone is a triterpenoid found in Brazilian propolis[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].
Tenofovir-C3-O-C15-CF3 (ammonium) exhibits substantially longer t1/2 values than tenofovir in human liver microsomes, potent anti-HIV activity in vitro, and enhances pharmacokinetic properties in vivo.
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
Ingenol-3-palmitate, an ingenane diterpenoid, is a nature product that could be isolated from the roots of Euphorbia ebracteolata. Ingenol-3-palmitate is a potent HIV-1 (HIV) inhibitor with an IC50 value of 4.1 nM[1].
(R)-Edelfosine ((R)-ET-18-OCH3) is a ether lipid analog with anti-HIV and antineoplastic activity[1].
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.
HIV-1 inhibitor-32 (compound 3c) is a potent HIV-1 inhibitor with an IC50 value of 34 nM for WT HIV-1. HIV-1 inhibitor-32 can be used for researching AIDS[1].
1,6,11-Trimethyl-1,2-dihydrofuro[2',3':1,2]phenanthro[4,3-d]oxazole (compound 1) is a potent anti-HIV-1 agent[1].
Tenofovir dsoproxil is a nucleotide reverse transcriptase inhibitor to treat HIV and chronic Hepatitis B.
HIV-1 inhibitor-52 is a potent broad-spectrum HIV-1 activity inhibitor with EC50s of 1.6 nM-6.4 nM for WT HIV-1, HIV-1 V370A, HIV-1 ΔV370, HIV-1 V362I/V370A, HIV-1 T332S/V362I/prR41G, HIV-1 A326T/V362I/V370A, HIV-1 R361K/V362I/L363M[1].
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
Elsulfavirine is a reverse transcriptase inhibitors for HIV-1 infection and is a new anti-HIV drug[1].
Tipranavir inhibits the enzymatic activity and dimerization of HIV-1 protease, exerts potent activity against multi-protease inhibitor (PI)-resistant HIV-1 isolates with IC50s of 66-410 nM.
Ditiocarb (Diethyldithiocarbamic acid) is an accelerator of the rate of copper cementation. Ditiocarb (Diethyldithiocarbamic acid) reduces the incidence of HIV infection, and also enhances adjuvant immunotherapy of high risk breast cancer[1][2][3].
Tsugafolin (compound 4) is a dehydroflavone with weak anti-HIV activity (IC50=118 μM) and devoid cytotoxicity (<150 μM). Tsugafolin can be isolated from Vitex leptobotrys[1].
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].
B07 hydrochloride is a CCR5 antagonist-based inhibitor of HIV-1 entry.
Suvizumab (KD-247) is an neutralizing antibody anti-HIV-1. Suvizumab reduces the viral load in HIV-infected patients. Suvizumab has good tolerance in human body and can be used to prevent HIV infection[1][2].