HIV-1 Inhibitor

Chloroquine is an antimalarial and anti-inflammatory agent widely used to treat malaria and rheumatoid arthritis. Chloroquine is an autophagy and toll-like receptors (TLRs) inhibitor. Chloroquine is highly effective in the control of SARS-CoV-2 (COVID-19) infection in vitro (EC₅₀=1.13 μM).

Doxorubicin hydrochloride (Hydroxydaunorubicin hydrochloride; ADR), a cytotoxic anthracycline antibiotic, is an anti-cancer chemotherapy agent. Doxorubicin hydrochloride is a potent human DNA topoisomerase I and topoisomerase II inhibitor with IC₅₀s of 0.8 μM and 2.67 μM, respectively. Doxorubicin hydrochloride reduces basal phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase. Doxorubicin hydrochloride induces apoptosis and autophagy.

Plerixafor (AMD 3100) is a selective CXCR4 antagonist with an IC₅₀ of 44 nM. Plerixafor, an immunostimulant and a hematopoietic stem cell (HSC) mobilizer, is an allosteric agonist of CXCR7. Plerixafor inhibits HIV-1 and HIV-2 replication with an EC₅₀ of 1-10 nM.

Hydroxyurea is a cell apoptosis inducer that inhibit DNA synthesis through inhibition of ribonucleotide reductase. Hydroxyurea shows anti-orthopoxvirus activity.

Efavirenz (DMP 266) is a potent inhibitor of the wild-type HIV-1 reverse transcriptase with a K_i of 2.93 nM and exhibits an IC₉₅ of 1.5 nM for the inhibition of HIV-1 replicative spread in cell culture.

Miltefosine is a broad spectrum antimicrobial, anti-leishmanial, phospholipid agent acting by inhibiting the PI3K/Akt activity. Miltefosine is an inhibitor of CTP-phosphocholine cytidyltransferase (CCT).

Chloroquine phosphate is an antimalarial and anti-inflammatory agent widely used to treat malaria and rheumatoid arthritis. Chloroquine phosphate is an autophagy and toll-like receptors (TLRs) inhibitor. Chloroquine phosphate is highly effective in the control of SARS-CoV-2 (COVID-19) infection in vitro (EC₅₀=1.13 μM).

Maraviroc (UK-427857) is a selective CCR5 antagonist with activity against human HIV.

CK-666 is a cell-permeable actin-related protein Arp2/3 complex inhibitor (IC₅₀=12 μM). CK-666 binds to Arp2/3 complex, stabilizes the inactive state of the complex, blocking movement of the Arp2 and Arp3 subunits into the activated filament-like (short pitch) conformation.

Ivermectin (MK-933) is a broad-spectrum anti-parasite agent. Ivermectin (MK-933) is a specific inhibitor of Impα/β1-mediated nuclear import and has potent antiviral activity towards both HIV-1 and dengue virus. It is a positive allosteric effector of P2X₄ and the α7 neuronal nicotinic acetylcholine receptor (nAChRs). Ivermectin also inhibits bovine herpesvirus1 (BoHV-1) replication and inhibits BoHV-1 DNA polymerase nuclear import. Ivermectin is a candidate therapeutic against SARS-CoV-2/COVID-19.

Ebselen (SPI-1005), a glutathione peroxidase mimetic, is a potent voltage-dependent calcium channel (VDCC) blocker. Ebselen potently inhibits M^pro (IC₅₀=0.67 μM) and COVID-19 virus (EC₅₀=4.67 μM).Ebselen is an inhibitor of HIV-1 capsid CTD dimerization. Ebselen, an organoselenium compound, can permeate the blood-brain barrier and has anti-inflammatory, antioxidant and anticancer activity.

Plerixafor octahydrochloride (AMD3100 octahydrochloride) is a selective CXCR4 antagonist with an IC₅₀ of 44 nM.

Scutellarin, an active flavone isolated from Scutellaria baicalensis, can down-regulates the STAT3/Girdin/Akt signaling in HCC cells, and inhibits RANKL-mediated MAPK and NF-κB signaling pathway in osteoclasts. Scutellarin is active against HIV-1IIIB, HIV-1(74V) and HIV-1KM018 with EC₅₀s of 26 μM, 253 μM and 136 μM, respectively.

Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI), widely used to treat HIV infection.

Betulinic acid is a natural pentacyclic triterpenoid, acts as a eukaryotic topoisomerase I inhibitor, with an IC₅₀ of 5 μM, and possesses anti-HIV, anti-malarial, anti-inflammatory and anti-tumor properties. Betulinic acid can cross the blood-brain barrier.

Rottlerin, a natural product purified from Mallotus Philippinensis, is a specific PKC inhibitor, with IC₅₀ values for PKCδ of 3-6 μM, PKCα,β,γ of 30-42 μM, PKCε,η,ζ of 80-100 μM. Rottlerin acts as a direct mitochondrial uncoupler, and stimulates autophagy by targeting a signaling cascade upstream of mTORC1. Rottlerin induces apoptosis via caspase 3 activation. Rottlerin inhibits HIV-1 integration and Rabies virus (RABV) infection.

Tenofovir (GS 1278; PMPA) is a nucleotide reverse transcriptase inhibitor to treat HIV and chronic Hepatitis B (HBV).

α-Lipoic Acid (Thioctic acid) is an antioxidant, which is an essential cofactor of mitochondrial enzyme complexes. α-Lipoic Acid inhibits NF-κB-dependent HIV-1 LTR activation. α-Lipoic Acid induces endoplasmic reticulum (ER) stress-mediated apoptosis in hepatoma cells. α-Lipoic Acid can be used with CPUL1 (HY-151802) to construct the self-assembled nanoaggregate CPUL1-LA NA, which has improved antitumor efficacy than CPUL1.

Lopinavir (ABT-378) is a highly potent, selective peptidomimetic inhibitor of the HIV-1 protease, with K_is of 1.3 to 3.6 pM for wild-type and mutant HIV protease. Lopinavir acts by arresting maturation of HIV-1 thereby blocking its infectivity. Lopinavir is also a SARS-CoV 3CL^pro inhibitor with an IC₅₀ of 14.2 μM.

Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) with an EC₅₀ value of 0.01 μM in PBMC cells. Emtricitabine inhibits HIV reverse transcriptase, preventing RNA from being transcribed into DNA. Emtricitabine has low brain permeability (logP <0)[1][2][3][4][5].