Antimicrobial and Antiviral (SARS-CoV-2) Potential of Cannabinoids and Cannabis sativa: A Comprehensive Review

Abstract

Antimicrobial resistance has emerged as a global health crisis and, therefore, new drug discovery is a paramount need. Cannabis sativa contains hundreds of chemical constituents produced by secondary metabolism, exerting outstanding antimicrobial, antiviral, and therapeutic properties. This paper comprehensively reviews the antimicrobial and antiviral (particularly against SARS-CoV-2) properties of C. sativa with the potential for new antibiotic drug and/or natural antimicrobial agents for industrial or agricultural use, and their therapeutic potential against the newly emerged coronavirus disease (COVID-19). Cannabis compounds have good potential as drug candidates for new antibiotics, even for some of the WHO’s current priority list of resistant pathogens. Recent studies revealed that cannabinoids seem to have stable conformations with the binding pocket of the Mpro enzyme of SARS-CoV-2, which has a pivotal role in viral replication and transcription. They are found to be suppressive of viral entry and viral activation by downregulating the ACE2 receptor and TMPRSS2 enzymes in the host cellular system. The therapeutic potential of cannabinoids as anti-inflammatory compounds is hypothesized for the treatment of COVID-19. However, more systemic investigations are warranted to establish the best efficacy and their toxic effects, followed by preclinical trials on a large number of participants.

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

“…The first compound identified by Krejčí with antibiotic activity was named cannabidiolic acid (CBDA) [56,57]. From then on, several other Cannabis components with antibiotic activities have been isolated and characterized [48,[58][59][60][61][62][63], which will be further discussed below. In 1956, L. Ferenczy published a paper documenting that plant seeds from various plant species, including those from Cannabis sativa, exhibited antibacterial activity, especially against Gram-positive bacteria [64].…”

“…There are some lines of evidence for an anti-viral activity of phytocannabinoids [60,264]. Some phytocannabinoids, especially ∆ 9 -THC and CBD, bind to the M pro protease of SARS-CoV-2, which plays a role in viral replication [60,264].…”

“…There are some lines of evidence for an anti-viral activity of phytocannabinoids [60,264]. Some phytocannabinoids, especially ∆ 9 -THC and CBD, bind to the M pro protease of SARS-CoV-2, which plays a role in viral replication [60,264]. CBGA and CBDA were found to be allosteric and orthosteric ligands for the spike protein of SARS-CoV-2 and prevented infection of human epithelial cells by a pseudovirus expressing the SARS-CoV-2 spike protein [265].…”

The Antimicrobial Properties of Cannabis and Cannabis-Derived Compounds and Relevance to CB2-Targeted Neurodegenerative Therapeutics

“…The authors conclude that a combination of CBDA and CBGA may represent a greater adjunctive challenge to SARS-CoV-2 spread. Recent reviews of the cannabis-related, SARS-CoV-2-specific literature, which accentuate the need for further research including clinical trials, are available [ 15 , 73 , 74 ].…”

“…Ongoing research on CIMPs as antimicrobial agents has been largely predicated by, primarily, Eastern European literature from the mid-twentieth century [ 6 , 7 , 8 , 9 , 10 ]. There have been a number of recent reviews published that highlight the potential of CIMPs as novel anti-microbial agents [ 8 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. With this recent revitalization of the field, the purpose of the present article, then, is (a) to update and augment the rapidly expanding literature, with a particular focus on the most recent developments; (b) to compare variant CIMP antimicrobial activities, where quantified; (c) to address specific mechanisms of CIMP–microbe interactions in greater depth; (d) to highlight the many major knowledge gaps alongside barriers to translation; (e) to discuss the potent antimicrobial activities of some CB2 receptor agonists which should be considered when designing therapeutic treatments for neurocognitive disorders; and, particularly, (f) that non-microbicidal CB2 agonists could be preferentially designed, engineered and utilized for long-term anti-neuropathic purposes, where appropriate.…”