Compounds | Targets | Mechanisms | Viruses | Clinical Status |
---|---|---|---|---|
1. Anionic polymers | ||||
Polysulfates (PVAS) Polysulfonates (PVS) Polycarboxylates Polyoxometalates Chicoric acid, zintevir, cosalane derivatives | Virus adsorption (i.e., interaction between HIV gp120 and CD4 receptor) | Interaction with viral envelope glycoprotein (i.e., V3 loop of) gp120 | HIV and other enveloped viruses (RSV, HSV, CMV, etc.) | As vaginal microbicides (under consideration) in the prevention of sexual HIV transmission |
2. Receptor antagonists | ||||
Bicyclams (i.e., AMD3100) T-22, T-134, ALX-40-4C, CGP-64222, TAK-779 | Virus-cell entry (fusion) | Interaction with CXCR4 or CCR5, the co-receptors for entry of T-tropic (X4) and M-tropic (R5) HIV strains, respectively | HIV FIV SIV | Systemic treatment of HIV infection (under clinical development) |
3. NRTIs | ||||
AZT, ddI, ddC, d4T, 3TC, ABC, and other ddN analogs | Substrate (dNTP)-binding site of RT (following intracellular phosphorylation to the 5′-triphosphate) | Chain termination after incorporation of the ddN 5′-monophosphate at the 3′-end of the viral DNA chain | HIV (and other retroviruses) | AZT, ddI, ddC, d4T, 3TC, ABC formally approved for the treatment of HIV infection (others are under clinical development) |
4. NNRTIs | ||||
Nevirapine, delavirdine, efavirenz, emivirine (MKC-442), capravirine, thiocarboxanilide UC-781, etc. | Nonsubstrate-binding site of HIV-1 RT | Inhibition of HIV-1 RT through interaction with allosteric pocket site | HIV-1 | Nevirapine, delavirdine, and efavirenz formally approved for the treatment of HIV infection (others are under clinical development) |
5.Acyclic guanosine analogs and 5-substituted 2′-deoxyuridines | ||||
Acyclovir, valaciclovir, penciclovir, famciclovir, bromovinyldeoxyuridine (BVDU) | Herpesviral DNA polymerase (following intracellular phosphorylation to the triphosphate) | First phosphorylation step by the virus-encoded TK. Incorporated at 3′-end (acyclovir) or via internucleotide linkage (BVDU) | HSV VZV | Formally approved for the systemic and/or topical treatment of HSV and/or VZV infections |
6. Acyclic nucleoside phosphonates | ||||
Cidofovir | DNA-viral DNA polymerase | Chain termination after incorporation at the 3′-end of the viral DNA chain | Herpes-, adeno-, pox-, polyoma-, and papillomaviruses | CMV retinitis (approved in AIDS patients) |
Adefovir dipivoxil | HIV and HBV RT | HIV, HBV | Phase III (HBV) | |
Tenofovir disoproxil | HIV and HBV RT (for all three, following intracellular phosphorylation to the diphosphate) | HIV, HBV | Phase III (HIV) | |
7. AICAR analogs | ||||
(Ribavirin, EICAR, etc.) Mycophenolic acid | IMP dehydrogenase (apoenzyme or coenzyme) | Inhibition of apoenzyme after intracellular phosphorylation to the 5′-monophosphate (ribavirin) or inhibition of coenzyme (mycophenolic acid), ultimately leading to a suppression in the supply of GTP and dGTP | Broad spectrum of (+)RNA viruses and (−)RNA viruses | Ribavirin approved for treatment of RSV and HCV infections (for the latter, in combination with interferon-α) |
8. Adenosine analogs | ||||
Neplanocin A, 3-deazaneplanocin A, 6′-C-methylneplanocin A, DHCeA, c3DHCeA, etc. | SAH hydrolase | Inhibition of methylation reactions that depend on SAM as methyl donor, ultimately leading to inhibition of maturation of viral mRNAs | Broad spectrum of (−)RNA viruses | Under consideration for the treatment of filo (i.e., Ebola) virus infections |
AICAR, 5-amino-4-imidazolecarboxamide ribonucleotide; DHCeA, 9-(trans-2′,trans-3′-dihydroxycyclopent-4′-enyl)adenine; c3DHCeA, 9-(trans-2′,trans-3′-dihydroxycyclopent-4′-enyl)-3-deazaadenine.