Table 1.
Antiviral activity of nucleoside analogs discussed in the review
| Compound | Trivial name, code, systematic name | Virus* | IC50 (EC50), μM | Reference |
|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 |
| 9 | Idoxuridine, IdU, 5-iodo-2'-deoxyiodouridine | HSV | 0.37 | 66 |
| 10 | Trifluridine, TFT, 5-trifluoromethyl-2'-deoxyuridine | HSV | 0.88 | 67 |
| 11 | Brivudine, BvdU, (E)-5-(2-bromovinyl)-2'-deoxyuridine | VSV, HSV | 0.033 | 68 |
| 12 | 6-Azauridine |
DENV, WNV, YFV ZIKV HCoV-NL63 |
0.1–0.5 1.5 0.03 |
3 3 61 |
| 13 | 5-AZC, 5-azacytidine | HIV-1 | 57 | 69 |
| 14 | Decitabine, 5-aza-2'-deoxycytidine | HIV-1 | 0.354 | 70 |
| 15 | Ribavirin, RBN, 1-β-D-ribofuranosyl-1,2,4-triazol-3-carboxamide |
HBV VSV RSV H1N1 SARS-CoV MERS-CoV |
43.8 82 25 2.5 50–819 20 |
71 6 6 72 61 61 |
| 16 | Viramidine, taribavirin, 1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine |
H1N1 RSV |
8 65 |
72 73 |
| 17 | EICAR, 1-β-D-ribofuranosyl-5-ethynyl-4-carboxamide |
CMV H1N1 RSV VSV Coxsackie B3 |
1.5 3.4 0.75 15 7.5 |
6 6 6 6 |
| 18 | EICAR, 1-β-D-ribofuranosyl-5-ethynyl-4-carboxamide |
CMV H1N1 RSV VSV Coxsackie B3 |
1.5 3.4 0.75 15 7.5 |
6 6 6 6 |
| 17 | triazoleZidovudine, AZT, 3'-azido-3'-deoxythymidine |
ANDV DENV HTNV |
4.4 9.5 10 |
74 75 74 |
| 20 | Zidovudine, AZT, 3'-azido-3'-deoxythymidine |
HIV HBV |
0.03 >100 |
2 76 |
| 21 | 4'-Azidothymidine |
HIV-1 HBV |
0.01 0.63 |
13 13 |
| 22 | 4'-Azido-2'-deoxy-5-methylcytidine | HBV | 5.99 | 13 |
| 23 | 2'-Deoxy-2'-β-fluoro-4'-azidocytidine | HBV | 0.12 | 13 |
| 24 | Balapiravir, R-1626, 4'-azido-2',3',5'-tri-O-isopropanoylcytidine | HCV | 1.3 | 15 |
| 25 | Mericitabine, RGT-7128, 2'-deoxy-2'-α-fluoro-3',5'-di-O-isopropanoyl-2'-β-methylcytidine | HCV | 4.6 | 77 |
| 26 | AadA, 2-amino-4'-azido-2'-deoxyadenosine |
HIV-1 HBV |
0.003 0.006 |
17 17 |
| 27 | AdG, 4'-azido-2'-deoxyguanosine |
HIV-1 HBV |
0.0005 0.009 |
17 17 |
| 28 | CadA, 2-amino-4'-cyano-2'-deoxyadenosine |
HIV-1 HBV |
0.0003 0.0003 |
17 17 |
| 29 | CdG, 4'-cyano-2'-deoxyguanosine |
HIV-1 HBV |
0.0004 0.0004 |
17 17 |
| 30 | Festinavir, censavudine, BMS-986001, 4'-ethynyl-3'-deoxy-2',3'-didehydrothymidine | HIV-1 | 0.002–0.008 | 78 |
| 31 | Islatravir, EfdA, МK-8591, 4'-ethynyl-2-fluoro-2'-deoxyadenosine | HIV-1 | 0.003 | 79 |
| 32 | 2-Amino-4'-vinyl-2'-deoxyadenosine |
HIV-1 HBV |
0.004 0.005 |
17 17 |
| 33 | 2-Amino-4'-trifluoromethyl-2'-deoxyadenosine |
HIV-1 HBV |
0.003 0.004 |
17 17 |
| 34 | 2-Amino-4'-ethyl-2'-deoxyadenosine |
HIV-1 HBV |
0.009 0.025 |
17 17 |
| 35 | 4'-Vinyl-2'-deoxyguanosine |
HIV-1 HBV |
0.004 0.002 |
17 17 |
| 36 | 4'-Trifluoromethyl-2'-deoxyguanosine |
HIV-1 HBV |
0.027 0.005 |
17 17 |
| 37 | 4'-Ethyl-2'-deoxyguanosine |
HIV-1 HBV |
0.006 0.008 |
17 17 |
| 38 | Gemcitabine, 2',2'-difluoro-2'-deoxycytidine |
HIV-1 HCV MERS-CoV SARS-CoV |
0.016. 0.012 1.22 4.96 |
70 80 61 61 |
| 40 | 2'-Ethinyladenosine | DENV | 1.41 | 3 |
| 41 | NITD008, 2'-ethynyl-7-deazaadenosine |
DENV ZIKV |
0.46 0.241 |
3 3 |
| 42 | GS-441524, 1'-cyano-7,9-dideaza-4-azaadenosine |
YFV DENV HCV SARS-CoV EBOV RSV |
11 9.46 4.1 2.24 0.78 0.53 |
3 3 20 20 21 21 |
| 43 | 1'-Cyano-2'-fluoro-2'-deoxy-7,9-dideaza-4-azaadenosine | EBOV, RSV, HCV | >200 | 21 |
| 44 | Didanosine, ddI, 2',3'-dideoxyinosine | HIV | 0.049 | 2 |
| 45 | Zalcitabine, ddC, 2',3'-dideoxycytidine | HIV | 0.6 | 2 |
| 46 | Stavudine, d4T, 3'-deoxy-2',3'-didehydrothymidine |
HIV-1 HIV-1 HIV-2 HIV-1 HIV-1 |
0.009 0.43 0.6 0.4 0.02–0.05 |
22 45 47 57 78 |
| 47 | d4C, 2',3'-dideoxy-2',3'-didehydrocytidine | HIV-1 | 0.005 | 22 |
| 48 | D-Fd4C, 5-fluoro-2',3'-dideoxy-2',3'-didehydrocytidine | HIV | 0.046 | 23 |
| 49 | Elvucitabine, L-Fd4C, (–)-L-(1S,4R)-5-fluoro-2',3'-didehydro-2',3'-dideoxycytidine | HIV | 0.034 | 24 |
| 50 | Lamivudine, 3TC, (–)-L-(1S,4R)-2',3'-dideoxy-3'-thiacytidine |
HIV-1 HBV |
0.002 0.01 |
25 25 |
| 51 | (+)-D-BCH-189, (+)-(1R,4S)-2',3'-dideoxy-3'-thiacytidine |
HIV-1 HBV |
0.2 0.5 |
25 25 |
| 52 | Emtricitabine, (–)-L-FTC, (–)-L-(1S,4R)-5-fluoro-2',3'-dideoxy-3'-thiacytidine |
HIV-1 HBV |
0.008 0.01 |
25 25 |
| 53 | (+)-D-FTC, (+)-D-(1R,4S)-5-fluoro-2',3'-dideoxy-3'-thiacytidine |
HIV-1 HBV |
0.84 0.96 |
25 25 |
| 54 | Apricitabine, (–)-D-dOTC, ATC, (–)-D-(1R,4R)-2'-deoxy-3'-oxa-6'-thiocytidine |
HIV-1 HIV-1 |
0.2 0.36 |
26 27 |
| 55 | (+)-L-dOTC, (+)-L-(1S,4S)-2'-deoxy-3'-oxa-6'-thiocytidine | HIV-1 | 0.28 | 26 |
| 56 | (–)-D-β-Dioxolane-T, (–)-D-1-[(2R,4R)-2-(hydroxymethyl)-1,3-dioxolan-4-yl]thymine | HIV | 0.39 | 28 |
| 57 | (+)-L-β-Dioxolane-T, (+)-L-1-[(2S,4S)-2-(hydroxymethyl)-1,3-dioxolan-4-yl]thymine | HIV | 4.81 | 28 |
| 58 | (+)-D-1-[(2R,4R)-2-(Hydroxymethyl)-1,3-dioxolan-4-yl]cytosine |
HIV HBV |
0.016 0.01 |
28 28 |
| 59 | Troxacitabine, BCH-4556, (−)-L-β-dioxolane-C, (–)-L-[(2S,4S)-2-(hydroxymethyl)-1,3-dioxolan-4-yl]cytosine |
HIV HBV |
0.002 0.0005 |
28 28 |
| 60 | Aristerоmycin, Ari, Ado, 6'-deoxyadenosine |
VV VSV Coxsackie B4 |
2.6 0.75 7.5 |
30 30 30 |
| 61 | Neplanocin A, 4',6'-didehydro-6'-deoxyadenosine |
VV VSV Coxsackie B4 |
0.11 0.04 0.15 |
30 30 30 |
| 62 | Abacavir, ABC, 2-amino-10-cyclopropyl-2',3'-dideoxy-2',3'-didehydro-6'-deoxyadenosine | HIV-1 | 4.0 | 81 |
| 63 | Carbovir, CBV, 2',3'-dideoxy-2',3'-didehydro-6'-deoxyguanosine | HIV-1 | 4.6 | 81 |
| 64 | Entecavir, ETV, 2'-deoxy-6'-methylidene-6'-deoxyguanosine |
HIV-1 HBV HBV |
1.0 0.0007 0.00018 |
76 76 82 |
| 74 | Nikavir, 3'-azido-3'-deoxythymidine-5'-phosphite | HIV | 1.0 | 41 |
| 80 | TriPPPro-d4TTP, 3'-deoxy-2',3'-didehydrothymidine-5'-[bis(4-aroyloxyphenyl)] triphosphate | HIV-1 | 0.03–0.07 | 45 |
| 81 | TriPPPro-CBVTP, 2',3'-dideoxy-2',3'-didehydro-6'-deoxyguanosine-5'-[bis(4-aroyloxyphenyl)] triphosphate | HIV-1 | 0.99 | 36 |
| 86 | cycloSal-d4T, (3'-deoxy-2',3'-didehydrothymidin-5'-yl)(cyclosaligenyl) monophosphate | HIV-1 | 0.15 | 47 |
| 87 | ddA, 2',3'-dideoxyadenosine | HIV-1 | 4.33 | 48 |
| 88 | cycloSal-ddA, (2',3'-dideoxyadenosin-5'-yl)(cyclosaligenyl) monophosphate | HIV-1 | 0.03 | 49 |
| 89 | d4A, 2',3'-dideoxy-2',3'-didehydroadenosine | HIV-1 | 30 | 49 |
| 90 | cycloSal-d4A, (2',3'-dideoxy-2',3'-didehydroadenosin-5'-yl)(cyclosaligenyl)-monophosphate | HIV-1 | 0.065 | 49 |
| 91 | cycloSal-ABC, {(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-ylmethyl}(cyclosaligenyl) monophosphate | HIV-1 | 0.95 | 50 |
| 92 | cycloSal-CBC, [(1S,4R)-4-(2-amino-6-oxo-9H-purin-9-yl)-2-en-1-ylmethyl](cyclosaligenyl) monophosphate | HIV-1 | 0.15 | 50 |
| 93 | cycloSal-BvdU, [2'-deoxy-5-(2-bromovinyl)uridin-5'-yl](cyclosaligenyl) monophosphate | EBV | 1.8 | 46 |
| 101 |
ProTide-d4T, 3'-deoxy-5'-О-[4-(trifluoromethyl)phenoxy(О-methylalanino)phosphoryl]-2',3'-didehydrothymidine ProTide-d4T, 3'-deoxy-5'-О-[3-(trifluoromethyl)phenoxy(О-methylalanino)phosphoryl]-2',3'-didehydrothymidine |
HIV-1 HIV-1 |
0.037 0.041 |
57 57 |
| 108 | Sofosbuvir, isopropyl (S)-2-({[(2R,3R,4R,5R)-3-hydroxy-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-methyl-4-fluorotetrahydrofuran-2-yl]methoxy}(phenoxy)phosphoryl)aminopropionate |
HCV DENV ZIKV |
0.52 1.4 1.0–32 |
55 83 84 |
| 110 | Remdesivir, GS-5734, (2-ethylbutyl) (S)-[({[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-cyanotetrahydrofuran-2-yl]methoxy}(phenoxy)phosphoryl)amino]propionate |
SARS-CoV MERS-CoV EBOV RSV HCV |
0.07 0.03–0.07 0.066 0.021 0.18 |
61 61 85 85 86 |
*ANDV – Andes orthohantavirus; CMV – cytomegalovirus of the herpes virus family; Coxsackie virus – Coxsackie viruses of the enterovirus family; DENV – dengue virus; EBOV – Ebola virus; EBV – herpes virus type 4; H1N1 – one of the influenza A viruses; HBV – hepatitis B virus; HCoV-NL63 – human coronavirus of the Netherlands; HCV – hepatitis C virus; HIV – human immunodeficiency virus; HSV – herpes simplex virus; HTNV – Hantaan orthohantavirus (one of the causative agents of hemorrhagic fever); MERS-CoV – Middle Eastern coronavirus strain; RSV – human respiratory syncytial virus; SARS-CoV – the coronavirus strain that caused the COVID-19 epidemic; VSV – vesicular stomatitis virus; VV – vaccinia virus; WNV – West Nile virus; YFV – yellow fever virus; ZIKV – Zika virus.