Antimicrobial and Antiviral (SARS-CoV-2) Potential of Cannabinoids and Cannabis sativa: A Comprehensive Review
Abstract
:1. Introduction
2. Antibacterial Activity of Cannabinoids and C. sativa
2.1. Historical Overview
2.2. Antibacterial Activities of Cannabinoids against Pathogens in the WHO’s Priority List
2.3. Antibacterial Activities of Cannabinoids against Pathogenic Bacteria Not on the WHO Priority List
3. Antifungal Activity
4. Antiviral Activity: Special Focus on SARS-CoV-2
4.1. Antiviral Efficacy against Viral Pathogens
4.2. SARS-CoV-2
5. Mode of Action of Cannabinoids
6. Factors Affecting Antimicrobial and Antiviral Activities of Phytocompounds, EOs and Extracts
6.1. Physical Factors
6.2. Structure
6.3. Synergism
7. Potential Application of Antimicrobial Properties of Cannabinoids in Non-Drug Agents
7.1. Cosmetics (Toothpaste)
7.2. Food Plants
7.3. Crop Protection
7.4. Others Application
8. Challenge vs. Opportunity as a Pharmaceutical Drug
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ACE2 | Angiotensin-converting enzyme 2 |
AIDS | Acquired immunodeficiency syndrome |
ARDS | Acute respiratory distress syndrome |
CBC | Cannabichromene |
CBCA | Cannabichromenic acid |
CBD | Cannabidiol |
CBDA | Cannabidiolic acid |
CBDV | Cannabidivarin |
CBDVM | Cannabidivarin methyl ester |
CBE | Cannabielsoin |
CBG | Cannabigerol |
CBL | Cannabicyclol |
CBN | Cannabinol |
CBT | Cannabitriol |
CBV | Cannabivarin |
CDC | Centers for disease control and prevention |
CNS | Central nervous system |
DNA | Deoxyribonucleic acid |
EC | Endocannabinoid |
EO | Essential oil |
FDA | Food and drug administration |
GNB | Gram-negative bacteria |
GPB | Gram-positive bacteria |
HMVEC | Human microvascular endothelial cells |
HOMO | Highest occupied molecular orbital |
IL | Interleukin |
KSHV | Kaposi sarcoma associated herpesvirus |
LPS | Lipopolysaccharide |
LUMO | Lowest unoccupied molecular orbital |
MBEC | Minimum biofilm eradication concentration |
MD | Molecular dynamic |
MIC | Minimum inhibitory concentration |
MRSA | Methicillin-resistant Staphylococcus aureus |
MSSA | Methicillin-susceptible Staphylococcus aureus |
MV | Membrane vesicle |
PBP | Penicillin-binding proteins |
QIDP | Qualified infectious disease product |
QSAR | Quantitative structure-activity relationship |
RNA | Ribonucleic acid |
R&D | Research and Development |
SARS-CoV | Severe acute respiratory syndrome coronavirus |
THC | Tetrahydrocannabinol |
THCA | Tetrahydrocannabinolic acid |
TMPRSS2 | Transmembrane protease, serine 2 |
TNF-α | Tumor necrosis factor |
VISA | Vancomycin-intermediate Staphylococcus aureus |
VRSA | Vancomycin-resistant Staphylococcus aureus |
WHO | World health organization |
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Pathogen | Compound/Extract/EO | Activity | Reference Antibiotic | Ref | |
---|---|---|---|---|---|
Antibiotic | Activity | ||||
Gram+ve | |||||
Enterococcus faecium | EO, α-humulene, α-pinene, β-pinene, myrcene | MIC 0.75–1.87 (%v/v) MBC 1.39–2.83 (%v/v) | [93] | ||
E. faecium | EO, α-humulene, α-pinene, β-pinene, myrcene | MIC 1–4 µg/mL | Ciprofloxacin | MIC 8 µg/mL | [94] |
EMRSA 15 and EMRSA 16 | CBD, THC, CBG, CBC, CBN | MIC 0.5–2.0 µg/mL | [95] | ||
MRSA | 4-acetoxy-2-geranyl-5-hydroxy-3-n-pentylphenol and 8-hydroxycannabinolic acid A | IC50 6.7 µM | Ciprofloxacin | IC50 0.4 µM | [96] |
MRSA | CVDVM | MIC 15.6 µM | [52] | ||
MRSA | CBCA | MIC 3.9 µM | [52] | ||
MRSA | CBD | MIC 1 µg/mL | Tobramycin, Meropenem, Ofloxacin | MIC 1, 16, 64 µg/mL (respectively) | [50] |
MRSA | CBD | MBEC 2–4 µg/mL | [49] | ||
MRSA | CBD analogs | MIC 0.25–64.0 µg/mL | Vancomycin, Daptomycin, Mupirocin | MIC 0.125–2.0 µg/mL | [49] |
MRSA | CBD, CBN, CBC, CBDV and Δ1 & 9-THC | IC50 5.8–10.6 µM | Ciprofloxacin | IC50 9.33 µM | [97] |
MRSA | CBDA | MIC 4 µg/mL | Tobramycin, Meropenem, Ofloxacin | MIC 1, 16, 64 µg/mL (respectively) | [50] |
MRSA | CBG | MIC 2 µg/mL and MBEC 4 µg/mL | [43] | ||
MRSA | EO | IC50 0.82–4.22 µg/mL | [98] | ||
MRSA, VISA, VRSA, E. faecium | CBD | MIC 1–2 µg/mL | Vancomycin, Daptomycin, Trimethoprim, Mupirocin, Clindamycin | MIC 0.125 to >64 µg/mL | [49] |
Streptococcus pneumoniae | CBD | MIC 1–4 µg/mL | Vancomycin, Daptomycin, Trimethoprim, Mupirocin, Clindamycin | MIC 0.25 to >64 µg/mL | [49] |
VRE | CBCA | MIC 7.8 µM | [52] | ||
Gram -ve | |||||
Escherichia coli | Aqueous extract | MIC 7.14 mg/mL | Ciprofloxacin | MIC < 0.12 mg/mL | [99] |
E. coli | N-p-trans-coumaroyl-tyramine | IC50 0.8 µg/mL | Ciprofloxacin | IC50 0.01 µg/mL | [100] |
E. coli | Seed extract | MIC 25 µg/mL | [67] | ||
E. coli and Salmonella typhimurium | Seed extract | Growth inhibition at 1 mg/mL | [101] | ||
E. coli, and Pseudomonas aeruginosa | EO | MIC 1.2 mg/mL | MIC 0.062–1.0 mg/mL | [60] | |
Enterobacter aerogenes | Seed extract | MIC 2.5 mg/mL | [101] | ||
Neisseria gonorrhoeae | CBD | MIC 1–2 µg/mL | Vancomycin, Levofloxacin, Meropenem, Gentamicin | MIC 0.002–4.0 µg/mL | [49] |
N. gonorrhoeae | CBD analogs | MIC 0.03–16.0 µg/mL | Mupirocin Colistin | MIC 1–32 µg/mL | [49] |
P. aeruginosa | Aqueous extract | MIC 7.14 mg/mL | Ciprofloxacin | MIC 1.23 mg/mL | [99] |
P. aeruginosa | Whole plant extract | MIC 12.5 µg/mL | [67] |
Pathogen | Compound/Extract/EO | Activity | Reference Antibiotic | Ref | |
---|---|---|---|---|---|
Antibiotic | Activity | ||||
Gram+ve | |||||
Bacillus subtilis and Staphylococcus aureus | Leaf extract | MIC 1.56 mg/mL | [81] | ||
B. subtilis, S. aureus and Micrococcus luteus | EO | MIC 1.2–4.7 mg/mL | Ciprofloxacin | MIC 0.015–0.031 mg/mL | [60] |
B. subtilis, S. aureus, Mycobacterium smegmatis | CBC, its homologs and isomers | MIC 0.39–3.12 µg/mL | [112] | ||
Clostridium species *, Enterococcus hirae *, Streptococcus salivarius * | EO, α-humulene, α-pinene, β-pinene, myrcene | MIC ≥ 0.8 (%v/v) | [93] | ||
Enterococcus *, Staphylococcus *, and Bacillus species * | EO | MIC ≥ 0.5 µg/mL | Ampicillin, Ciprofloxacin | MIC ≥ 0.25 µg/mL | [94] |
Listeria monocytogenes strains * | EO | MIC/MBC 2.5–5.0 μL/mL | [110] | ||
L. monocytogenes * | EO | MIC ≥ 1 µg/mL | Ampicillin | MIC ≥ 0.25 µg/mL | [94] |
L. monocytogenes * | EO, α-pinene, Myrcene | MBC ≥ 1024 µg/mL | [111] | ||
Lancefield Group A Streptococcus sp. | Leaf extract | MIC 20 mg/mL MBC 30 mg/mL | [113] | ||
MRSA biofilms * | Seed extract | MIC 1 mg/mL | [101] | ||
MSSA | CBCA | MIC 7.8 µM | [52] | ||
MSSA, VISE, Staphylococcus epidermidis, Staphylococcus pyogenes, Enterococcus faecalis, Cutibacterium acnes, Clostridioides difficile | CBD | MIC 0.5–4.0 µg/mL | Vancomycin, Daptomycin, Trimethoprim, Mupirocin, Clindamycin, Levofloxacin, Meropenem, Gentamicin, Erythromycin, Tetracycline, Mupirocin | MIC 0.03–64.0 µg/mL | [49] |
Mycobacterium intracellulare | CBG | IC50 15 µg/mL | [114] | ||
S. aureus | 4-acetoxy-2-geranyl-5-hydroxy-3-n-pentylphenol, 8-hydroxycannabinolic acid A | IC50 3.5 µM | Ciprofloxacin | IC50 0.4 µM | [96] |
S. aureus | Aqueous extract | MIC 3.57 mg/mL | Ciprofloxacin | MIC 0.62 µg/mL | [99] |
S. aureus | Methanol extract | MIC 25 µg/mL | [67] | ||
S. aureus (including multi drug resistant S. aureus 104) | EO | MIC 8 mg/mL | [61] | ||
S. aureus (mature and pre-formed biofilms) | EO | MBEC 24 mg/mL | [61] | ||
S. aureus and E. faecalis | Seed extract | MIC 1 mg/mL | [101] | ||
S. aureus biofilm * | EO | MIC 0.5 mg/mL | [101] | ||
S. aureus planktonic cells * | EO | MIC 1 mg/mL | [101] | ||
S. aureus * | EO | MIC 1.25–5.0 µg/mL | [110] | ||
S. aureus * | EO | MIC 1–4 µg/mL | Ciprofloxacin | MIC 0.5–16.0 µg/mL | [94] |
S. aureus, S. epidermidis | CBD, CBDA | MIC 1–4 µg/mL | Torbamycin, Meropenem, Ofloxacin | MIC 0.06–0.5 µg/mL | [50] |
SA-1199B (MDR), RN4220 (Macrolide-resistant), XU212 (Tetracycline-resistant) | CBD, CBC, THC, CBG, CBN, Carboxylated versions, Abnormal cannabinoids | MIC 0.5–4.0 µg/mL | [95] | ||
Staphylococcus species | THC, CBD | MIC 1–5 µg/mL | [115] | ||
Staphylococcus, Lactococcus and Bacillus species | CBD, CBN, CBC, CBDV and Δ1 & 9-THC | IC50 2.6–9.2 µM | Ciprofloxacin | IC50 0.003–2.4 µM | [97] |
Gram-ve | |||||
Moraxella catarrhalis, Neisseria meningitidis and Legionella pneumophila | CBD | MIC 0.25–1.0 µg/mL | Vancomycin, Levofloxacin, Meropenem, Gentamicin | MIC 0.03–32 µg/mL | [49] |
Pectobacterium carotovorum subsp. carotovorum * | EO, α-humulene, α-pinene, β-pinene, myrcene | MIC ≥ 1.24 (%v/v) | [93] | ||
Pseudomonas fluorescens and Xanthobacter flavus | CBD, CBN, CBC, CBDV and Δ1 & 9-THC | IC50 3.1–9.3 µM | Ciprofloxacin | IC50 0.15–2.3 µM | [97] |
Pseudomonas species | EO(s) and Terpenes | MIC 1.05–1.97 (%v/v) | [93] |
Pathogen | Compound/Extract/EO | Activity | Reference Antibiotic | Ref | |
---|---|---|---|---|---|
Antibiotic | Activity | ||||
Candida albicans | Extract | MIC 0.25 mg/mL | [124] | ||
C. albicans | Extract | MIC 1.42 mg/mL | Fluconazole | MIC 2 mg/mL | [99] |
C. albicans | 4-terpenyl cannabinolate | MIC 8.5 µg/mL | [125] | ||
C. albicans | 8-hydroxycannabinol | IC50 4.6 µM | Amphotericin B | IC50 0.3 µM | [96] |
C. albicans | Cannabis and ginger blend | MIC 4.69 mg/mL | [126] | ||
C. albicans | CBDV | IC50 11.9 mM | Nystatin | IC50 1.50 mM | [97] |
C. albicans | CBNA | IC50 8.5 µg/mL | [125] | ||
Candida krusei | Cannabinoids | IC50 53.4–60.5 µM | amphotericin B | IC50 0.7 µM | [96] |
Candida neoformans | β-caryophyllene/oxide | IC50 1.18–19.4 µg/mL | [98] | ||
Candida species | β-caryophyllene | MIC 1.45–10.0 µg/mL | [98] | ||
Plasmodium falciparum | Cannabinoids | IC50 4.0–6.7 µM | Chloroquine | IC50 0.1–0.5 µM | [96] |
P. falciparum | CBNA | IC50 2.4–2.7 µg/mL | [125] | ||
Trichophyton and Arthroderma species | EO | MIC 0.312–6.3 µg/mL | Griseofulvin | MIC 1.26 to >8.0 µg/mL | [123] |
Virus | Compound | Activity (µM) | Ref |
---|---|---|---|
Epstein–Barr virus (EBV) | THC | IC50 3.0 | [140] |
Hepatitis C virus (HCV) | CBD | EC50 3.16 | [143] |
Herpes simplex virus (HSV) | THC | IC50 1.9 | [140] |
Kaposi sarcoma associated herpesvirus (KSHV) | THC | IC50 3.3 | [140] |
KSHV | CBD | IC50 2.08 | [144] |
Murine gamma herpesvirus 68 (MHV) | THC | IC50 1.9 | [140] |
Corona Virus Group | Compound | Activity (µM) | Reference Drug | Activity (μM) | Ref |
---|---|---|---|---|---|
hCov-OC43 | Caflanone | EC50 0.42 | [184] | ||
SARS-CoV-2 (spike positive) | CBD | EC50 0.64–1.79 | [195] | ||
SARS-CoV-2 in A549-ACE2 | 7-OH-CBD | EC50 3.6 | [195] | ||
SARS-CoV-2 | CBD, THC, CBN, CBDA, THCA | IC50 7.91–37.61 | Remdesivir, Lopinavir and Chloroquine | IC50 8.17–13.16 | [189] |
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Mahmud, M.S.; Hossain, M.S.; Ahmed, A.T.M.F.; Islam, M.Z.; Sarker, M.E.; Islam, M.R. Antimicrobial and Antiviral (SARS-CoV-2) Potential of Cannabinoids and Cannabis sativa: A Comprehensive Review. Molecules 2021, 26, 7216. https://doi.org/10.3390/molecules26237216
Mahmud MS, Hossain MS, Ahmed ATMF, Islam MZ, Sarker ME, Islam MR. Antimicrobial and Antiviral (SARS-CoV-2) Potential of Cannabinoids and Cannabis sativa: A Comprehensive Review. Molecules. 2021; 26(23):7216. https://doi.org/10.3390/molecules26237216
Chicago/Turabian StyleMahmud, Md Sultan, Mohammad Sorowar Hossain, A. T. M. Faiz Ahmed, Md Zahidul Islam, Md Emdad Sarker, and Md Reajul Islam. 2021. "Antimicrobial and Antiviral (SARS-CoV-2) Potential of Cannabinoids and Cannabis sativa: A Comprehensive Review" Molecules 26, no. 23: 7216. https://doi.org/10.3390/molecules26237216