Table 1.
Selected scientific articles of compounds with therapeutic potential for SARS-CoV-2 targets
| Compound/concentration | Main results | Type of study |
|---|---|---|
| Flavonoid artemetin (0.75 and 1.5 mg/kg) (Achillea millefolium L. – Asteraceae) | Intravenous injection of artemetin in anesthetized rats significantly reduced the hypertensive response to angiotensin I. Artemetin (1.5 mg/kg) was also able to reduce plasma (37%) and vascular (63%) angiotensin-converting enzyme (ACE) activity. These effects may be associated of ability to decrease angiotensin II generation in vivo, by ACE inhibition | Preclinical in vivo [39] |
| Allyl disulfide and alyl trisulfide/concentration not informed (Allium sativum L. – Amaryllidaceae) | Organosulfur compounds found in garlic essential oil have inhibitory effect in amino acids of the ACE2 protein and the main protease PDB6LU7 of SARS-CoV-2 | Molecular docking [40] |
| Allicin (15, 30 and 45 mg · kg-1 · day-1) via daily intra-gastric gavage for 12 weeks (A. sativum) | In streptozotocin (STZ)-induced diabetic rats, allicin reversed the albuminuria STZ-induced diabetic rats | Preclinical in vivo [44] |
| 1% high cholesterol diet (HCD) plus allicin (10 mg/kg/day) for 4 weeks (A. sativum) | In rabbits, allicin supplementation significantly decreased serum CRP and significantly protected against HCD-induced attenuation of rabbit aortic | Preclinical in vivo [51] |
| Diallyl sulfide (DAS) and diallyl disulfide (DADS) (200 µM was administrated twice orally with an interval of 12 h) for 5 consecutive days (A. sativum) | DAS or DADS given twice significantly decreased the plasma levels of IL-6 and significantly reduced the plasma levels of C-reactive protein (CRP) in diabetic mice | Preclinical in vivo [36] |
| DAS (100 mg/kg) was orally administered for 4 days (A. sativum) | DAS afforded renal and neuroprotection against cyclophosphamide (CP)-induced nephropathic encephalopathy in rats due to its capacity to significantly decrease CRP and IL-6 levels | Preclinical in vivo [52] |
| The intraperitoneally injected with 1 mL of CSE on days 1, 8, and 15 along with the daily injection of DADS (100 and 10 mg/kg/day) for 21 days (A. sativum) | In rat emphysema model by intraperitoneal injection of cigarette smoke extract (CSE), DADS exerted an anti-inflammation effect on emphysema rats through suppressing IL-6 cytokine production. Furthermore, the regulation effects of DADS on CD4⁺ and CD8⁺ T cells were observed | Preclinical in vivo [37] |
| 13 mL of rapeseed oil enriched with 0.23 mL DADS (100 mmol/L) intragastrically (A. sativum) | Stimulation of ferritin at the RNA and protein levels was found in rats administered a DADS-enriched oil solution. The expression of the transferrin receptor, an iron transporter, was also enhanced by DADS in rat liver | Preclinical in vivo [38] |
| S-allycysteine (SAC) was administered orally (150 mg/kg b.w/rat) for 45 days (A. sativum) | The levels of albumin were increased in SAC treated diabetic rats | Preclinical in vivo [45] |
| SAC (150 mg/kg b.w/rat) in aqueous solution orally for 45 days (A. sativum) | The levels of transferrin in tissues were increased in SAC-treated STZ-induced diabetic rats, suggest that SAC could have a protective effect against alterations in oxidative stress induced iron metabolism in the diabetic state | Preclinical in vivo [56] |
| Two intraperitoneally injections of aloe-emodin (50 mg/kg; CCl4+ aloe-emodin) (Aloe vera L. – Asphodelaceae) | In a rat model of carbon tetrachloride (CCl4) intoxication six rats treated with aloe-emodin, albumin mRNA expression was significantly lower only in the liver of CCl4 rats | Preclinical in vivo [46] |
| Cytopiloyne at 25 µg/kg body weight three times per week (Bidens pilosa L. – Asteraceae) | Cytopiloyne promotes the differentiation of type 2 Th cells, which is consistent with it enhancing GATA-3 transcription. Also, does not compromise total antibodies (Ab) responses mediated by T cells in female NOD mice | Preclinical in vivo [57] |
| Centaurein (75 µg/ml) (B. pilosa) | Centaurein regulated IFN-gamma (IFN-γ) transcription, probably via Nuclear factor of activated T-cells (NFAT) and factor nuclear kappa B (NF-kB) in T cells | Preclinical in vivo [58] |
| C57BL/6 J mice were intraperitoneally injected with centaurein at 20 μg (B. pilosa) | Centaurein increased the IFN-γ expression in T and NK cells and the serum IFN-γ level in mice. Centaurein elevated the transcription of T-bet which is consistent with its effect on that of IFN-γ | Preclinical in vivo [59] |
| C1 (1E,6E)-1,2,6,7-tetrahydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl) hepta-1,6-diene-3,5-dione) and C2 (4Z,6E)-1,5-dihydroxy-1,7-bis(4-hydroxyphenyl) hepta-4,6-dien-3-one (Curcuma longa L. – Zingiberaceae) | Compounds C1 and C2 showed minimum binding score (−9.08 and −8.07 kcal/mole) against Mpro protein (protease (Mpro) of the SARS-CoV2). These two compounds strongly bind to the catalytic core of the Mpro protein with higher efficacy than lopinavir, a standard antiretroviral of the protease inhibitor class | X-ray crystallographic structure [67] |
| Bioavailable curcumin diet (protein 34.2%, fat 16.5%, starch 28%, Bio-curcumin (BCM-95; Frutarom, Londerzeel, Belgium) 0.09% diet) (C. longa) | Eight obese cats were fed to diet for two 8-week periods (cross-over study design) while maintaining animals in an obese state. Curcumin resulted in lower plasma α1-acid glycoprotein (AGP) concentration but not changed haptoglobin levels | Clinical trial [30] |
| 500 mg curcumin capsules (total: 1,000 mg) twice daily for 12 weeks (C. longa) | In 34 β-thalassemia patients, curcumin treatment significantly reduced serum levels of nontransferrin bound iron (NTBI), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and not affected the transferrin saturation | Randomized controlled trial [31] |
| 1,500-mg curcumin daily for 10 weeks (C. longa) | In 22 patients with Type 2 diabetes, curcumin treatment the mean concentration of high-sensitivity CRP besides serum concentrations of triglyceride decreased | Randomized controlled trial [32] |
| Curcuminoids (500 mg TID per oral; n = 45) for a period of 4 weeks (C. longa) | Curcuminoids were significantly efficacious in modulating all assessed inflammatory mediators: IL-6, tumor necrosis factor-α (TNF-α), CRP, calcitonin gene related peptide (CGRP), substance P and monocyte chemotactic protein-1 (MCP-1) in 45 male subjects who were suffering from chronic sulfur mustard-induced pulmonary complications | Randomized controlled trial [53] |
| Curcumin thrice a week at a dose level of 50 mg/kg b.w were administered for 9 consecutive weeks (C. longa) | In 8 rats curcumin treatment effectively reduced the IL-6 and CRP levels in blood serum prevented the Benzo(a)pyrene-induced lung injury | Preclinical in vivo [33] |
| 500 mg (one capsule) of curcumin with each meal (three times/day after meal) for 16 weeks (C. longa) | During the trial (4 months) in 23 patients with T2DM, the curcumin treatment significantly reversed albuminuria | Randomized controlled trial [34] |
| 200 µg of curcumin was i.p. injected daily until day 6 (C. longa) | In mice, curcumin significantly increased CXCR5 + B-cell lymphoma 6+ TFH cells and CD95+ GL-7+ germinal center B cells in draining lymph nodes. Total Ab production as well as high affinity Immunoglobulin G (IgG1 and IgG2b) Ab production was induced | Preclinical in vivo [35] |
| Tetrahydrocurcumin (THC) 120 mg/kg per day, and 1 kg of the AIN 93 G diet contained 800 mg of THC, day 0 to day 25 (C. longa) | THC had beneficial effects on 13 asthmatic mice such pathological changes (eosinophils hyper-production), Th17 and T cell subsets and attenuating the Th2 response | Preclinical in vivo [60] |
| Diet containing 1% curcumin until the end of the study (C. longa) | In New Zealand Black/White F1 female mice starting at 18 weeks of age with lupus nephritis (LN), curcumin induced the protective effects at least in part by its interaction with regulatory T (Treg) cells | Preclinical in vivo [18] |
| Trans-anethole (FEO) (130 mg/kg FEO, thrice weekly for 1 week, by rubbing on shaved rat dorsal area) (Foeniculum vulgare Mill. – Apiaceae) | In six rats, hepatic dysfunction study indicates promising significant amelioration of liver function reflected in ALT, AST, alkaline phosphatase (ALP), bilirubin, albumin plasma levels by FEO treatment | Preclinical in vivo [47] |
| Trans-anethole (FEO) (36.4, 72.8 or 145.6 mg/kg) once per day for 7 consecutive days (F. vulgare) | In acute lung injury (ALI)-bearing mice, FEO treatment eliminated LPS‑induced histopathological changes, decreased the number of inflammatory cells, and reduced in IL-17 mRNA expression. In addition, trans‑anethole increased IL-10 mRNA expression in lung tissues and resulted in a marked elevation in Treg cells and reduction in Th17 cells in spleen tissues | Preclinical in vivo [61] |
| Pinitol (0.05%, P-I and 0.1% pinitol, P-II) for 10 weeks (Glycine max L. Merrill – Fabaceae) | Pinitol supplementation with a high cholesterol (HFHC) diet (10% coconut oil plus 0.2% cholesterol) in hamsters fed-high fat was very effective on the elevation of antiatherogenic factors, including plasma HDL-cholesterol, apolipoprotein A-I (APO A-I), adiponectin, and paraoxonase (PON) activity | Preclinical in vivo [66] |
| 56 mg isoflavones/day for 17 day each with a 25-day washout period between treatments (G. max) | In 22 young healthy, normolipidemic subjects (5 men and 17 women) soy protein with intact phytoestrogens (contained 0.9 mg (3.5 µM) daidzein and 1.0 mg (3.7 µM) genistein) increases HDL-cholesterol and APO A-I concentrations | Controlled trial [20] |
| Isoflavone (80 mg day-1, n = 100) for 24 weeks (G. max) | In patients with ischemic stroke isoflavone therapy caused a significant decrease in serum levels of CRP and IL-6 levels | Randomized controlled trial [21] |
| Isoflavone (80 mg/day, n = 50) for 12 weeks (G. max) | In patients with prior ischemic stroke, isoflavone treatment resulted in a significant decrease in serum CRP levels and improved brachial flow-mediated dilatation in patients with clinically manifest atherosclerosis, thus reversing their endothelial dysfunction status | Randomized controlled trial [22] |
| Soy isoflavones (genistein) 40 mg/day for 6 months (G. max) | Genistein does not interfere in high-sensitive serum CRP levels in 20 healthy postmenopausal women | Randomized controlled trial [23] |
| Genistein (0.5, 1.0, or 2.0 mg (kg body mass) (−1); by subcutaneous injection) for 8 weeks (G. max) | In the liver injury induced in rats by thioacetamide revealed that the treatment of genistein decreased the elevated serum levels of AST, ALT and total and direct bilirubin, and increased the serum level of albumin | Preclinical in vivo [24] |
| Genistein (300 mg/kg/day) was administered orally for 24 weeks (G. max) | In streptozotocin STZ-induced diabetic rats, administration of genistein resulted in a decrease in blood glucose, % glycosylated hemoglobin (HbA1c), CRP and in augmentation of total antioxidant reserve of the hearts | Preclinical in vivo [25] |
| Genistein (20 mg/kg) administered 10 days before to 10 days after the tumor induction (G. max) | In adult female C57BL/6 mice, genistein significantly increased lymphocyte proliferation and LDH release. Furthermore, the treatment caused a significant increment in IFN-γ levels and achieved significant therapeutic effect in tumor model of Human Papillomavirus (HPV) associated-cervical cancer | Preclinical in vivo [26] |
| Active compound soybean ACE2 inhibitor (ACE2iSB) (G. max) | ACE2iSB strongly inhibited recombinant human (rh)ACE2 activity with an IC50 value of 84 nM. This is the first demonstration of an ACE2 inhibitor by HPLC-MS with fluorescence detection | HPLC-MS [41] |
| Daidzein (DAZ) at 10 mg/kg body weight dose by oral gavage daily for six weeks (G. max) | Adult Balb/c mice treated with DAZ increased the percentage of CD4⁺CD28⁺ T cells and DAZ also regulated B lymphopoesis | Preclinical in vivo [27] |
| Orally administered DAZ at various physiological doses (2–20 mg/kg body weight) during adulthood (G. max) | DAZ in female B6C3F1 mice, the T cell populations (CD3+ IgM-, CD4+ CD8- and CD4-CD8+) were increased. The activities cytotoxic T cells and natural killer cells were not altered. In NOD mice, DAZ modulated the antibody production, as shown by increased levels of IgG2b and IgG1. DAZ increased CD8+ CD25+ splenocytes in NOD females | Preclinical in vivo [28] |
| Intraperitoneally (IP) injection with lunasin at 0.4 or 4 mg/kg body weight (G. max) | In BALB/c mice lunasin inhibited the growth of (OVA) ovalbumin-expressing A20 B-lymphomas, which was correlated with OVA-specific CD8 + T cells. In addition, lunasin was an effective adjuvant for immunization with OVA, which together improved animal survival against lethal challenge with influenza virus expressing the major histocompatibility complex (MHC) class I OVA peptide SIINFEKL (PR8-OTI) | Preclinical in vivo [62] |
| Equol 20 mg/kg for 3 days by gavage (G. max) | In BALB/c mice treated with equol showed a significantly higher level of OVA-specific IgE. IL-13 (produced mainly by CD4⁺ T cells) production level was significantly higher than that control | Preclinical in vivo [29] |
| 7S globulin (Momordica charantia L. – Cucurbitaceae) | Study revealed that a tripeptide (VFK) from 7S globulin possess a higher binding affinity for ACE than reported drug Lisinopril (LPR) | Not mentioned [42] |
| Lectin 100 µg/ml (M. charantia) | Lectin is a T cell-independent B cell activator and a polyclonal immunoglobulin (Ig) inducer in BALB/c mice. Additionally, lectin was shown to upregulate the cell activation marker CD86, in a B cell subpopulation | Preclinical in vivo [63] |
| MAP30 (anti-HIV protein) 1 µM (M. charantia) | MAP30 was capable of inhibiting infection of HIV type 1 (HIV-1) in T lymphocytes and monocytes as well as replication of the virus in already-infected cells. Integration of viral DNA into the host chromosome is a vital step in the replicative cycle of retroviruses, including the AIDS virus. The inhibition of HIV-1 integrase by MAP30 suggests that impediment of viral DNA integration may play a key role in the anti-HIV activity | Genomic studies [19] |
| 1-Deoxynojirimycin (DNJ) 10 mg daily for 4 weeks (Morus indica L. – Moraceae) | In 72 patients with with coronary heart disease (CHD) and blood stasis syndrome (BSS) DNJ significantly reduced the levels of CRP, IL-6, TNF-α, malondialdehyde (MDA), Self-Rating Anxiety Scale (SAS) and Hamilton Depression Scale (HAMD) and BSS scores and increased superoxide dismutase (SOD) levels | Randomized controlled trial [54] |
| Phyllanthin and hypophyllanthin (50, 100, and 200 mg/kg) for next 28 day (Phyllanthus amarus Schumach. & Thonn. – Euphorbiaceae) | In Sprague Dawley rats by OVA-challenged, compounds significantly decreased the levels of albumin in serum, bronchoalveolar lavage fluid (BALF) and lungs. OVA-induced increase in IgE, oxidative-stress (SOD, GSH, MDA, NO, Nrf2 and iNOs), inflammatory makers (HO-1, TNF-α, IL-1β and IL-6) levels were significantly decreased by compounds | Preclinical in vivo [48] |
| Geraniin 5 mg/kg was orally administered once (P. amarus) | Spontaneously hypertensive rats, the geraniin showed antihypertensive activity in lowering systolic blood pressure and diastolic blood pressure. Geraniin also showed dose-dependent inhibitory activities against ACE (IC50 were 13.22 µM) | Preclinical in vivo [43] |
| (-)-Epicatechin 50 mg/kg body weight for 21 days (Phyllanthus niruri L. – Euphorbiaceae) | Albumin levels are depleted in hepatitic rats, (-)-epicatechin pretreatment increased albumin levels. Also, pretreatment decreased the tissue damage in hepatitis condition | Pre-clinical in vivo [49] |
| Punicalagin (10, 20, and 40 mg/kg/day, i.p.) for 11 days (Punica granatum L. – Lythraceae) | Acrylamide-induce toxicity in rat and decrease levels of serum protein and albumin concentration. Punicalagin recovered these levels | Preclinical in vivo [50] |
| 10-dehydrogingerdione (10 mg/kg body weight orally, see isolation and purification) (Zingiber officinale Roscoe – Zingiberaceae) | Six New Zealand male rabbits 10-dehydrogingerdione-treated daily during the 6 weeks showed a significant improvement in serum lipids and this effect was correlated to its ability to lower high sensitivity C-reactive protein (hsCRP), homocysteine and matrix metalloproteinase 9 (MMP9) levels | Preclinical in vivo [55] |
| Zerumbone (0.1, 1, and 10 mg/kg of body weight) orally fed from days 23 to 39 (Z. officinale) | In BALB/c mice asthmatic model compared to OVA-induced hallmarks of asthma, zerumbone induced higher IgG2a antibody production and promoted Th1 cytokine IFN-γ production | Preclinical in vivo [64] |
| 6-Gingerol (0.01%)-containing drinking water until the end of the experiments (100 days) (Z. officinale) | In female Balb/c and C57BL/6 (8–10 mice), 6-gingerol treatment caused massive infiltration of CD4 and CD8 T-cells and B220(+) B-cells, but reduced the number of CD4(+) Foxp3(+) regulatory T-cells | Preclinical in vivo [65] |
Source: Research data, 2021.