Table 1.
Proposed Mechanism of Action Detail and antiviral activities for Vif Inhibitors
| Compound (publication date, reference) |
Proposed Target |
A3G Deg. |
A3F Deg. |
A3G Dependent Antiviral Activity |
More A3G in Virus |
A3G hyper mutati ons |
Modeling predictions |
reported μM IC50 (cell type tested) |
Multiple Clades Tested |
Drug Resistant Strains Tested |
Counters creens to other HIV Targets |
|---|---|---|---|---|---|---|---|---|---|---|---|
| O2-16 (December 2016, 61) | Vif Multimerization | + | + | + | + | + | Binds Vif near PPLP | 0.17 (PBMC) | 16 isolates from all HIV clades | 7 mult-/single-drug resistant strains | PR, RT, IN and time-of-addition |
| N4.1analogs (February 2015, 67) | A3G-Vif interaction | + | + | + | + | ND | ND | 4.2 (PBMC) | 4 isolates | ND | + |
| IMB-26/35 (April 2010, 68) | A3G-Vif interaction | + | ND | + | + | + | ND | 0.017 (H9)* | ND | ND | (PR, RT, IN)* |
| Benzimidazole series | |||||||||||
| analogs 14/26 (April 2015, 69) | A3G-Vif interaction | + | ND | + | ND | ND | ND | 0.004/0.05 8 (H9) | ND | ND | ND |
| ZBMA-1 (June 2015, 70) | Vif-EloC interaction | + | ND | + | ND | ND | Binds EloC near Asp 111 | 1.01 (PBMC) | ND | ND | ND |
| RN-18 series | |||||||||||
| analog 12c/13a (January 2017, 73) | Vif-EloC interaction | + | ND | ND | ND | ND | Binds BC box region of Vif | 1.54/0.25 (H9) | 4 isolates | ND | ND |
| analog 5 (May 2012, 72) | ND | + | ND | + | ND | ND | ND | 1.1 (H9) | ND | ND | ND |
| RN-18 (October 2008, 71) | ND | + | + | + | ND | ND | ND | 6.0 (H9) | ND | ND | ND |
| Other compounds | |||||||||||
| Zif-15 (July 2017, 75) | Vif-EloC interaction | + | ND | ND | + | ND | Binds BC box region of Vif | ND | ND | ND | ND |
| VEC-5 (February 2012, 74) | Vif-EloC interaction | + | + | + | ND | ND | Binds Vif binding region of EloC | 24.5 (CEM) | ND | ND | + |
| hop-8 (September 2017, 76) | A3G expression | + | ND | +/− | + | ND | ND | 0.11 (PBMC) | 3 isolates | 3 drug resistant strains, ΔVif and HIV-2 | PR, RT, IN and ENV |
| Redoxal (October 2015, 78) | A3G expression | + | ND | + | ND | ND | ND | 1.4 (PBMC) | 3 isolates | ND | + |
| MM-1/2 (July 2014, 77) | A3G expression | + | ND | + | ND | ND | ND | ND | ND | ND | ND |
Footnote: ND = not determined
*
claimed in report with data not shown