| (1) Viral spike protein with human ACE2 interaction |
(A) Small molecule |
|
Small molecule and peptides are capable of preventing viral entry either by breaking the interaction or by inhibiting viral cell fusion with the host cell |
20 and 21
|
| 1. SSAA09E1 |
1. Effective if applied 1h post infection by breaking the interaction |
| 2. VE607 |
2. Blocks S1 protein RDB–ACE2 mediated cellular entry |
| (B) Peptide based |
|
70 and 73
|
| SBP1, inhibitors (1–4) |
Have identical sequences of amino acids to ACE2 and binds with the S1 portion of the viral spike protein |
| (2) Host proteases utilised by SARS-CoV-2 for viral entry |
|
|
Observed good results when a cathepsin L inhibitor is administered with a serine protease inhibitor; a significant increase in efficacy is observed in preventing viral cell entry |
|
| (A) Cysteine protease cathepsin L |
(A) SSAA09E1, K1777, glycopeptide e.g. teicoplanin |
(A) Inhibits S1/S2 cleavage at the tested concentration |
20, 26 and 27
|
| (B) Serine protease TMPRSS2 |
(B) Camostat mesylate |
(B) Inhibits host cell serine protease and prevents the cleavage of S1/S2 |
24 and 25
|
| (C) Other host proteases (furine) |
(C) dec-RVKR-cmk |
(C) A furin inhibitor that blocks the furin mediated cleavage of the S protein |
33 and 34
|
| (3) HR1 and HR2 interactions at the S2 subunit of the spike glycoprotein |
Peptide EK1C4 |
The peptide derived from HR2 binds with HR1, and a native complex cannot form |
Further modification of biomimetic peptides and in vivo efficacy in animal models can support the development of peptide based therapeutics |
80
|
| (4) Viral enzymes |
|
|
|
|
| (A) PLpro |
(A) GRL0617, 6577871 |
(A) Inhibits PLpro activity |
(A) Narrow spectrum |
46 and 47
|
| (B) 3CLpro |
(B) Lopinavir–ritonavir, nelfinavir, 13b |
(B) Inhibits 3CLpro activity |
(B) Ritonavir increases lopinavir pharmacodynamic and pharmacokinetic activities when used together |
40, 41, 43 and 48
|
| (C) RNA dependent RNA-polymerase (RdRp) |
(C) Remdesivir (GS-5734), ribavirin |
(C) Nucleoside analog drugs function via inserting into viral RNA chains, causing their premature termination, and they are also used for post-infection treatment |
(C) Active against SARS and MERS coronaviruses in in vitro studies at high doses |
50, 51, 54–57 and 59
|
| (D) Helicase |
(D) SSYA10-001 |
(D) Inhibits helicase unwinding and ATPase activities |
(D) Inhibits the activity of a broad range of corona viruses |
61–64
|
