Table 1.
Characteristic features of anti-viral peptides effective against SARS-CoV-2
| Target protein | Target domain | Name | Sequence derived from | Sequence/IUPAC name | IC50 | Reference |
|---|---|---|---|---|---|---|
| Spike protein | RBD | Inhibitor 1 | ACE2 (21–55) | IEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNIT | - | [35] |
| Inhibitor 2 | ACE2 (21–88 and 349–357) |
|
- | |||
| Inhibitor 3 | ACE2 (21–105 and 323–362) |
|
- | |||
| Inhibitor 4 | ACE2 (21–95 and 335–400) |
|
- | |||
| Spike protein | RBD | AVP0671 | Peptide library | TWLATRGLLRSPGRYVYFSPSASTWPVGIWTTGELVLGCDAAL | - | [30] |
| ACE2 | RBD-binding site | AVP1244 | Peptide library | GCASRCKAKCAGRRCKGWASAFRGRCYCKCFRC | - | [30] |
| Spike protein | RBD | 18aa | ACE (28–45) | FLDKFNHEAEDLFYQSSL | - | [22] |
| 23aa | ACE (23–45) | EQAKTFLDKFNHEAEDLFYQSSL | - | |||
| Spike protein | RBD | Peptide 1 | EQEERIQQDKRKNEQEDKRYQRYGRGKGHQP | - | [32] | |
| Peptide 2 | EQQQRIQEDQYRNDWEDEEYQRKGRGKGHQP | - | ||||
| Peptide 3 | EQQQRIQQDQDSNDREDKEYQKRGKGKGHNH | - | ||||
| Peptide 4 | QEEQKIQEDQRRNDKEHKRKQRYGRGCGKQN | - | ||||
| Peptide 5 | EQEERIQRDKRKNEKEHEEKQRRGRGCGKQN | - | ||||
| Peptide 6 | EQEERIQQDKRKNENEDKRYQRYGRGKGHQP | - | ||||
| Peptide 7 | EQEERIQQDKRKNEWEDQYYQKYGQGKGHQP | - | ||||
| Peptide 8 | EQEERIQRDQYKNDYEDEEYQRKGRGKGHQP | - | ||||
| Peptide 9 | EQEQRIQQDKRSNEQEDKRYQREGKGKGHNN | - | ||||
| Peptide 10 | EQEERIQQDQRKNDKEDQRYQREGKGKGHNH | - | ||||
| Peptide 11 | ACE (22–53) | EEQAKTFLDKFNHEAEDLFYQSSGLGKGDFR | - | |||
| Peptide 12 | ACE (21–43) | IEEQAKTFLDKFNHEAEDLFYQS | - | |||
| Spike protein | RBD | satpdb12488 | PTTFMLKYDENGTITDAVDC | - | [33] | |
| satpdb14438 | SNNTIAIPTNFSISITTEVM | - | ||||
| satpdb28899 | RDVSDFTDSVRDPKTSEILD | - | ||||
| satpdb18674 | QYGSFCTQLNRALSGIAAEQ | - | ||||
| satpdb18446 | VLYNSTFFSTFKCYGVSATK | - | ||||
| Spike protein | RBD | [22–44] | ACE (22–44) | EEQAKTFLDKFNHEAEDLFYQSS | - | [21] |
| [22–57] | ACE (22–57) | EEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEE | - | |||
| [22–44-g-351-357] | ACE (22–44 and 351–357) | EEQAKTFLDKFNHEAEDLFYQSS G LGKGDFR | - | |||
| [351–357] | ACE (351–357) | LGKGDFR | - | |||
| Spike protein | RBD | pep1c | ACE (30–38) | DKFNHEAED | 3 · 3 ± 0 · 8 mM | [36] |
| pep1d | ACE (30–35) | DKFNHE | - | |||
| pep1e | ACE (37–42) | EDLFYQ | - | |||
| Spike protein | RBD | AHB1 | ACE2 | DEDLEELERLYRKAEEVAKEAKDASRRGDDERAKEQMERAMRLFDQVFELAQELQEKQTDGNRQKATHLDKAVKEAADELYQRVR | 35 nM | [37] |
| AHB2 | ACE2 | ELEEQVMHVLDQVSELAHELLHKLTGEELERAAYFNWWATEMMLELIKSDDEREIREIEEEARRILEHLEELARK | 15 · 5 nM | |||
| LCB1 | de novo design | DKEWILQKIYEIMRLLDELGHAEASMRVSDLIYEFMKKGDERLLEEAERLLEEVER | 23 · 54 pM | |||
| LCB2 | de novo design | SDDEDSVRYLLYMAELRYEQGNPEKAKKILEMAEFIAKRNNNEELERLVREVKKRL | - | |||
| LCB3 | de novo design | NDDELHMLMTDLVYEALHFAKDEEIKKRVFQLFELADKAYKNNDRQKLEKVVEELKELLERLLS | 48 · 1 pM | |||
| LCB4 | de novo design | QREKRLKQLEMLLEYAIERNDPYLMFDVAVEMLRLAEENNDERIIERAKRILEEYE | - | |||
| LCB5 | de novo design | SLEELKEQVKELKKELSPEMRRLIEEALRFLEEGNPAMAMMVLSDLVYQLGDPRVIDLYMLVTKT | - | |||
| LCB6 | de novo design | DREQRLVRFLVRLASKFNLSPEQILQLFEVLEELLERGVSEEEIRKQLEEVAKELG | - | |||
| LCB7 | de novo design | DDDIRYLIYMAKLRLEQGNPEEAEKVLEMARFLAERLGMEELLKEVRELLRKIEELR | - | |||
| LCB8 | de novo design | PIIELLREAKEKNDEFAISDALYLVNELLQRTGDPRLEEVLYLIWRALKEKDPRLLDRAIELFER | - | |||
| Spike protein | RBD | P1 | ACE | STIEE QAKTF LDKFN HEAED LFYQS SL-NH2 | - | [38] |
| P1scr | AHLFS YLTTK EEQDN DAIFL QEFSK ES-NH2 | - | ||||
| Ppen | IEE QAKTF LDKFN HEAED LFYQS-NH2 | - | ||||
| P2 | SALEE QLKTF LDKFL HELED LLYQL SL-NH2 | - | ||||
| P3 | SALEE QLKTF LDKFL HELED LLYQL AL-NH2 | - | ||||
| P4 | Ac-SALEE QLKTF LDKFL HELED LLYQL AL-NH2 | - | ||||
| P5 | SALEE QLKTF LDKFL HELED PLYQL AL-NH2 | - | ||||
| P6 | SALEE QLKTF LDKFL HELED LLYQL ALAL-NH2 | - | ||||
| P7 | SALEE QYKTF LDKFL HELED LLYQL ALAL-NH2 | >1 μM | ||||
| P8 | SALEE QLKTF LDKFM HELED LLYQL AL-NH2 | 46 nM | ||||
| P9 | SALEE QYKTF LDKFM HELED LLYQL SL-NH2 | 53 nM | ||||
| P10 | SALEE QYKTF LDKFM HELED LLYQL AL-NH2 | 42 nM | ||||
| Spike protein | RBD | Native (1) | ACE | IEEQAKTFLDKFNHEAEDLFYQS | - | |
| 2 | IR8EQAKTFS5DKFNHEAEDLFYQS | - | ||||
| 3 | IEEQR8KTFLDKS5NHEAEDLFYQS | - | ||||
| 4 | IEEQAR8TFLDKFS5HEAEDLFYQS | - | ||||
| 5 | IEEQAKTFR8DKFNHES5EDLFYQS | - | ||||
| 6 | IEEQAKTFLDKR8NHEAEDS5FYQS | - | ||||
| 7 | IEEQAKTFLDKFR8HEAEDLS5YQS | - | ||||
| 8 | IEEQAKTFLDKFNHER8EDLFYQS5 | - | ||||
| 9 | HEAEDLFYQS | - | ||||
| 10 | HES5EDLS5YQS | - | ||||
| 11 | IEEQAKTFLDKFNHE | - | ||||
| 12 | IEEQR8KTFLDKS5NHE | - | ||||
| 13 | TFLDKFNHEAEDL | - | ||||
| 14 | TFR8DKFNHES5EDL | - | ||||
| 15 | TS5LDKS5NHEAEDL | - | ||||
| α5β1 integrin | ACE2 and RBD-binding domain | ATN-161 | Fibronectin | Ac-PHSCN-NH2 | 3 · 16 nM | [52] |
| Spike S2 | HR1 | EK1 | HR2 (OC43) | SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKEL | 286 · 7 nM | [55] |
| EK1P | SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKEL-PEG4-Palm | 69 · 2 nM | ||||
| EK1C | SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKEL-PEG4-Chol | 48 · 1 nM | ||||
| EK1C1 | SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKEL-Chol | 56 · 8 nM | ||||
| EK1C2 | SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKEL-GSG-Chol | 48 · 2 nM | ||||
| EK1C3 | SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKEL-GSG-PEG4-Chol | 10 · 6 nM | ||||
| EK1C4 | SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKEL-GSGSG-PEG4-Chol | 1 · 3 nM | ||||
| EK1C5 | SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKEL-GSGSG-PEG8-Chol | 3 · 1 nM | ||||
| EK1C6 | SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKEL-GSGSG-PEG12-Chol | 3 · 9 nM | ||||
| EK1C7 | SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKEL-GSGSG-PEG24-Chol | 3 · 9 nM | ||||
| Spike S2 | HR1 | 2019-nCoV-HR2P | HR2 (1168–1203) | DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL | 0 · 18 μM | [56] |
| Spike S2 | HR1 | IPB01 | HR2 (1162–1205) | ISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL | 0 · 022 μM | [58] |
| IPB02 | ISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELK (Chol) | 0 · 025 μM | ||||
| IPB03 | INASVVNIQKEIDRLNEVAKNLNESLIDLQELGK (Chol) | 0 · 015 μM | ||||
| IPB04 | SVVNIQKEIDRLNEVAKNLNESLIDLQELGK (Chol) | 0 · 033 μM | ||||
| IPB05 | IQKEIDRLNEVAKNLNESLIDLQELGK (Chol) | >5 μM | ||||
| IPB06 | IDRLNEVAKNLNESLIDLQELGK (Chol) | >5 μM | ||||
| IPB07 | IQKEIDRLNEVAKNLNESLIDLQELGKYEQYIK (Chol) | 0 · 017 μM | ||||
| IPB08 | ISGINASVVNIQKEIDRLNEVAKNLNESLIK (Chol) | 4 · 66 μM | ||||
| IPB09 | SVVNIQKEIDRLNEVAKNLNESLIK (Chol) | >5 μM | ||||
| Spike S2 | HR1 | SARSHRC | HR2 (1168–1203) | DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL | - | [59] |
| SARSHRC-chol | DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL-chol | - | ||||
| SARSHRC-PEG4-chol | DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL-PEG4-chol | - | ||||
| SARSHRC-PEG24-chol | DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL-PEG24-chol | - | ||||
| [SARSHRC]2-PEG11 | [DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL]2-PEG11 | - | ||||
| [SARSHRC-PEG4]2-chol | [DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL-PEG4]2-chol | - | ||||
| Spike S2 | HR1 | Peptide #1 | HR2 (1164–1202 | VVNIQKEIDRLNEVAKNLNESLID | - | [60] |
| Peptide #2 | DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL | 1 μM | ||||
| Peptide #3 | DISGINASVVNIQKEIDRLNEVAKNLNESLIELQEL | 7 · 2 μM | ||||
| Peptide #4 | DISGINASVVNIQKEIDRLNEVAKNLNESLIKLQEL | - | ||||
| Peptide #5 | DISGINASVVNIQKEIDRLNEVAKNLNESLIGLQEL | 4 · 7 μM | ||||
| Peptide #6 | DISGINASVVNIQKEIDRLNEVAKNLGESLIGLQEL | - | ||||
| Peptide #7 | DISGINASVVNIQKEIDRLNEVAKNLPESLIGLQEL | - | ||||
| Peptide #8 | DISGINASVVNIQKEIDRLDEVAKNLNESLIDLQEL | - | ||||
| Peptide #9 | DISGINASVVNIQKEIDRLGEVAKNLNESLIDLQEL | - | ||||
| Peptide #10 | DISGINASVENIQKEIDRLNEVAKNLNESLIDLQEL | 8 · 9 μM | ||||
| Peptide #11 | DISGINASVVNIQKEIDRLNEVAKNLGESLIELQEL | - | ||||
| Peptide #12 | DISGINASVVNIQKEIDRLDEVAKNLPESLIELQEL | - | ||||
| Spike S2 | HR1 | Peptide 1 | HR2 (1163–1203) | GYHLMSFPQSAPHGVVFLHVTW | - | [61] |
| Peptide 2 | GVFVSNGTHWFVTQRNFYE | - | ||||
| Peptide 3 | ISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL | 0 · 72 μM | ||||
| Peptide 4 | IQKEIDRLNEVAKNLNESLIDLQELGK | - | ||||
| Furin | Catalytic domain | dec-RVKR-cmk | PCSK target motif | N-(1,20-diamino-9-(4-aminobutyl)-6-(2-chloroacetyl)-1,20-diimino-12-isopropyl-8,11,14-trioxo-2,7,10,13,19-pentaazaicosan-15-yl)decanamide | 0 · 057 μM | [67] |
| Probably catalytic domain | MI-1851 | Peptidomimetic | N-(1-((4-carbamimidoylbenzyl)amino)-4-(guanidinooxy)-1-oxobutan-2-yl)-2-(2-(2-(4-(guanidinomethyl)phenyl)acetamido)-3-guanidinooxy)propanamido)-3,3-dimethylbutanamide) | - | [70] | |
| TMPRSS2 | Catalytic site | Aprotinin | Natural polypeptide | RPDFC LEPPY TGPCK ARIIR YFYNA KAGLC QTFVY GGCRA KRNNF KSAED CMRTC GGA | - | [70,76] |
| MI-432 | Synthetic peptidomimetic | 3-(3-(4-(2-Aminoethyl)piperidin-1-yl)-2-((2’,4’-dichloro-[1,1’-biphenyl])-3-sulfonamido)-3-oxopropyl)benzimidamide | - | [70] | ||
| MI-1900 | Synthetic peptidomimetic | 4-(3-(3-Carbamimidoylphenyl)-2-((2’,4’-dimethoxy-[1,1’-biphenyl])-3-sulfonamido)propanoyl)-N-cyclohexylpiperazine-1-carboxamide | - | [70] | ||
| α1-Antitrypsin | Natural glycoprotein | Polypeptide (394 amino acids with three carbohydrate side chains) | 10–20 μM | [79,95] | ||
| Cathepsin L | Acidification | P9 | Mouse-β-defensin-4 derived | NGAICWGPCPTAFRQIGNCGHFKVRCCKIR | 2 · 4 μg/mL | [91] |
| P9R | Mouse-β-defensin-4 derived | NGAICWGPCPTAFRQIGNCGRFRVRCCRIR | 0 · 9 μg/mL | [91] | ||
| PA1 | Mouse-β-defensin-4 derived | NGAICWGPCPTAFRQIGNCGHFKVRCCKIRDED | - | [91] | ||
| P9RS | Mouse-β-defensin-4 derived | NGAHSWHPNETHFRQIHNSGRHRVRSHRIR | - | [91] | ||
| 8P9R | Mouse-β-defensin-4 derived | NGAICWGPCPTAFRQIGNCGRFRVRCCRIR | 0 · 3 μg/mL | [92] |
PCSK: Pro-protein convertase subtilisin/kexin