Inhibitors of viral replication |
Ribavirin |
RdRp, as nucleoside analog |
Lethal mutagenesis, Inhibition of nucleotide biosynthesis by inhibiting of viral RNA polymerase |
[24, 26] |
Remdesivir |
RdRp, as nucleoside analog |
Acting on viral RNA polymerase |
[41] |
Favipiravir |
RdRp |
Inhibition of transcription and replication of viral gene |
[60] |
Emtricitabine/tenofovir |
Viral reverse transcriptase |
Viral replication inhibitor |
[71] |
Oseltamivir |
Viral neuraminidase |
Viral replication inhibitor |
[72] |
Inhibitors of viral proteases |
Lopinavir/ritonavir |
Viral main proteases (e.g., 3CLp, Nsp3c) |
Blocks the multiplication cycle by inhibiting the viral proteases |
[87] |
Darunavir |
Viral main proteases (e.g., 3CLp, Nsp3c) |
Prevents the formation of mature infectious virus particles |
[11] |
Danoprevir |
Chymotrypsin-like protease |
Prevents the formation of mature virus particles |
[114] |
Atazanavir |
Viral protease (e.g., 3CLp), helicase |
Prevents the formation of mature virus particles |
[121, 122] |
Cobicistat |
Inhibition of human CYP3A proteins |
Helps to viral protease inhibitory effects |
[123, 124] |
Noscapine |
Binds to viral protease |
Prevents the formation of mature virus particles; anti-oxidant; anti-inflammatory |
[125, 128] |
Inhibitors of viral entry to host cell |
Baricitinib |
Janus kinase (JAK) enzymes |
Prevents viral entry into cells via (a) inhibits AP2-associated protein kinase 1 (AAK1) that promotes endocytosis of the virus, (b) interaction with cyclin G-associated kinase (GAK); anti-inflammatory |
[153–155] |
Ruxolitinib |
Janus kinase (JAK) enzymes |
Prevents viral entry into cells by inhibiting the viral clathrin-mediated endocytosis |
[157, 161] |
Chloroquine/Hydroxychloroquine |
The entry of extracellular zinc to intracellular lysosomes |
Inhibits viral entry; interferes with RdRp function; immunomodulatory effect |
[49, 130, 131, 133] |
Arbidol |
Viral fusion to host cell surface |
Inhibits viral entry; probably inhibits viral replication |
[71, 147] |
Recombinant human ACE2 (rhACE2) |
Spike protein |
Acts similarly to the ACE2 enzyme; prevent the viral attachment to host cell surface |
[162] |
Bromhexine |
Trans-membrane protease serine 2 (TMPRSS2) |
Inhibits viral entry and slows down the rate of virus replication |
[167, 168] |
Immunoenhancement agents |
Interferon-β |
– |
Increases the activity of immune system; activation of RNase that breaks down the nucleic acid chain of the virus; blocks the translation of mRNA; prevents encapsidation and viral release |
[182, 183] |
Interferon-α-1b/2b |
– |
Stimulates innate anti-viral responses |
[17] |
Nivolumab (Programmed cell death blocker) |
PD-1 as a specific marker on cytotoxic T lymphocytes |
Blocking immune checkpoint molecules and improves the T cell responses |
[187, 188] |
|
Levamisole |
– |
Enhances the cellular immunity; immunostimulatory and immunosuppressive functions |
[192] |
Immunomodulating agents |
intravenous immunoglobulin (IVIg); convalescent plasma |
– |
Improves the immunity by immunomodulatory and anti-inflammatory effects |
[197] |
Fingolimod |
Sphingosine-1 phosphate (S1P) receptors |
Reduces the lymphocytes egress from lymph nodes; inhibit angiogenesis during inflammation; promotes the endothelial barrier function; regulates the B cells and dendritic cells migration |
[204, 205] |
Thalidomide |
Suppresses the activation of NF-κB; down-regulation of selected cell surface adhesion molecules |
Suppression of excessive production of TNF-α; reduces the leukocyte migration |
[210] |
Immunosuppressive and anti-inflammatory agents |
Corticosteroids (methylprednisolone, ciclesonide) |
Phospholipase A2 |
Immunosuppressive activities; anti-inflammatory properties; reduces body temperature |
[213] |
Tocilizumab |
IL6- receptor |
Inhibits the IL-6 signal transduction |
[237] |
Sarilumab |
IL6- receptor |
Inhibits the IL-6 signal transduction |
[143] |
Siltuximab |
IL6 |
Neutralizes IL-6 bioactivity; enhances cytochrome P450 activity; decreases the levels of TNF-α, IL-1, CCL2, CXCL12, and VEGF |
[288, 289] |
NSAIDs (paracetamol, ibuprofen) |
Cyclooxygenase (COX) enzymes |
Anti-inflammatory effect by inhibiting of the prostaglandins production; |
[269] |
Eculizumab |
C5 complement protein |
Blocking the cleavage of complement protein C5 into C5a and C5b; decreases the inflammation and cell damages |
[262] |
Tetrandrine |
– |
Anti-inflammatory effect by inhibition of 5-lipoxygenase, IL-5, IL-6 and IL-1; anti-oxidant; anti-fibrogenic; immunomodulation; inhibition of platelet aggregation |
[267, 268] |
Pulmonary vaso-effectors |
Nitric oxide inhalation |
Smooth muscle cells in respiratory tract |
Vasodilator |
[271] |
Sildenafil |
Type 5 phosphodiesterase |
Increases the level of cGMP and induces vasodilatory effects |
[278, 279] |
Aviptadil |
Adenosine cyclase |
Increases the activity of adenosine cyclase; relaxation of cavernosal smooth muscle |
[281] |
Bevacizumab |
Vascular endothelial growth factor (VEGF) |
Prevents the angiogenic activity; decrease vascular permeability and pulmonary edema |
[282] |
|
Losartan |
Angiotensin II receptor |
Inhibition of smooth muscle constriction; anti-fibrotic role in lung injury and protects lung fibrosis |
[285] |
Others |
Mepolizumab |
IL-5 |
Anti-asthma; inhibiting ligand binding and decreasing peripheral blood eosinophils |
[287] |
Carrimycin |
Mycobacterium tuberculosis |
Anti-tuberculosis |
[286] |