Category Archives: Covid/SARS

New AKT-dependent mechanisms of anti-COVID-19 action of high-CBD Cannabis sativa extracts

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“COVID-19 is caused by the SARS-CoV-2 virus, which enters target cells via interactions with ACE2 and TMPRSS2. Here, we show AKT serine/threonine kinase-dependent epigenetic control of ACE2 and TMPRSS2 expression by high-cannabidiol (CBD) cannabis extracts and their individual components. CBD alone and extracts #1, #5, #7, and #129 downregulated ACE2 and TMPRSS2 in lung fibroblast WI-38 cells through AKT-mediated inhibition. miR-200c-3p and let-7a-5p were two contributing miRNAs in CBD-mediated suppression of ACE2 and TMPRSS2. CBD and terpene PTWT2.2 profoundly inhibited ACE2 and TMPRSS2 expression, both individually and in combination. Extracts #1, #5, #7, and #169 suppressed COX2 expression and remarkably attenuated TNFα/IFNγ-triggered induction of proinflammatory factors IL-6 and IL-8 by AKT pathway. The most abundant molecules present in extracts #1 and #7 modulated the expression of COX2, IL-6, and IL-8 both individually and in combination. These results reveal that high-CBD cannabis extracts attenuated ACE2 and TMPRSS2 expression and the induction of inflammatory mediators COX2, IL-6, and IL-8 via the AKT pathway, highlighting their potential anti-COVID-19 features.”

https://pubmed.ncbi.nlm.nih.gov/35277472/

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

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“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.”

https://pubmed.ncbi.nlm.nih.gov/34885798/

Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants

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“As a complement to vaccines, small-molecule therapeutic agents are needed to treat or prevent infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants, which cause COVID-19. Affinity selection-mass spectrometry was used for the discovery of botanical ligands to the SARS-CoV-2 spike protein. Cannabinoid acids from hemp (Cannabis sativa) were found to be allosteric as well as orthosteric ligands with micromolar affinity for the spike protein. In follow-up virus neutralization assays, cannabigerolic acid and cannabidiolic acid prevented infection of human epithelial cells by a pseudovirus expressing the SARS-CoV-2 spike protein and prevented entry of live SARS-CoV-2 into cells. Importantly, cannabigerolic acid and cannabidiolic acid were equally effective against the SARS-CoV-2 alpha variant B.1.1.7 and the beta variant B.1.351. Orally bioavailable and with a long history of safe human use, these cannabinoids, isolated or in hemp extracts, have the potential to prevent as well as treat infection by SARS-CoV-2.”

https://pubmed.ncbi.nlm.nih.gov/35007072/

Cannabidiol and Terpene Formulation Reducing SARS-CoV-2 Infectivity Tackling a Therapeutic Strategy

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“In late 2019, COVID-19 emerged in Wuhan, China. Currently, it is an ongoing global health threat stressing the need for therapeutic compounds. Linking the virus life cycle and its interaction with cell receptors and internal cellular machinery is key to developing therapies based on the control of infectivity and inflammation. In this framework, we evaluate the combination of cannabidiol (CBD), as an anti-inflammatory molecule, and terpenes, by their anti-microbiological properties, in reducing SARS-CoV-2 infectivity. Our group settled six formulations combining CBD and terpenes purified from Cannabis sativa L, Origanum vulgare, and Thymus mastichina. The formulations were analyzed by HPLC and GC-MS and evaluated for virucide and antiviral potential by in vitro studies in alveolar basal epithelial, colon, kidney, and keratinocyte human cell lines.

Conclusions and impact: We demonstrate the virucide effectiveness of CBD and terpene-based formulations. F2TC reduces the infectivity by 17%, 24%, and 99% for CaCo-2, HaCat, and A549, respectively, and F1TC by 43%, 37%, and 29% for Hek293T, HaCaT, and Caco-2, respectively. To the best of our knowledge, this is the first approach that tackles the combination of CBD with a specific group of terpenes against SARS-CoV-2 in different cell lines. The differential effectiveness of formulations according to the cell line can be relevant to understanding the pattern of virus infectivity and the host inflammation response, and lead to new therapeutic strategies.”

https://pubmed.ncbi.nlm.nih.gov/35242142/

Potential Neuroprotective Effect of Cannabinoids in Covid-19 Patients

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“The global pandemic caused by the SARS-CoV-2 virus began in early 2020 and is still present. The respiratory symptoms caused by COVID-19 are well established, however, neurological manifestations that may result from direct or indirect neurological damage after SARS-CoV-2 infection have been reported frequently. The main proposed pathophysiological processes leading to neurological damage in COVID-19 are cerebrovascular disease, and indirect mechanisms of inflammatory / autoimmune origin. A growing number of studies confirm that neuroprotective measures should be maintained in COVID-19 patients. On the other hand, cannabinoids have been the subject of various studies that propose them as potential promising drugs in chronic neurodegenerative diseases due to their powerful neuroprotective potential. In this review we address the possible mechanism of action of cannabinoids as a neuroprotective treatment in patients infected by SARS-CoV-2. The endocannabinoid system is found in multiple systems within the body, including the immune system. Its activation can lead to beneficial results, such as a decrease in viral entry, a decrease in viral replication, and a decrease in pro-inflammatory cytokines such as IL-2, IL-4, IL-6, IL-12, TNF-α or IFN-c through CB2R expression induced during inflammation by SARS-CoV-2 infection in the central nervous system.”

https://pubmed.ncbi.nlm.nih.gov/35382723/

In silico discovery of non-psychoactive scaffolds in Cannabis halting SARS-CoV-2 host entry and replication machinery

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“Aim: Coronavirus disease still poses a global health threat which advocates continuous research efforts to develop effective therapeutics. Materials & methods: We screened out an array of 29 cannabis phytoligands for their viral spike-ACE2 complex and main protease (Mpro) inhibitory actions by in silico modeling to explore their possible dual viral entry and replication machinery inhibition. Physicochemical and pharmacokinetic parameters (ADMET) formulating drug-likeness were computed. Results: Among the studied phytoligands, cannabigerolic acid (2), cannabigerol (8), and its acid methyl ether (3) possessed the highest binding affinities to SARS-CoV-hACE2 complex essential for viral entry. Canniprene (24), cannabigerolic methyl ether (3) and cannabichromene (9) were the most promising Mpro inhibitors. Conclusion: These non-psychoactive cannabinoids could represent plausible therapeutics with added-prophylactic value as they halt both viral entry and replication machinery.”

https://pubmed.ncbi.nlm.nih.gov/35399958/

Early Studies Suggest CBD May Help Prevent COVID-19

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“Cannabidiol (CBD) is a cannabis compound with some medicinal properties. The U.S. Food and Drug Administration (FDA) has approved one CBD-based medication to treat seizure disorders; other medications are in the development and testing pipeline.

Now some early studies show that CBD could help block infection with SARS-CoV-2, the virus that causes COVID-19.”

https://covid19.nih.gov/news-and-stories/early-studies-suggest-cbd-may-help-prevent-covid19

Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses

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“The spread of SARS-CoV-2 and ongoing COVID-19 pandemic underscores the need for new treatments. Here we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD inhibits SARS-CoV-2 replication in part by up-regulating the host IRE1α RNase endoplasmic reticulum (ER) stress response and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/ml oral solution per medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials.”

https://pubmed.ncbi.nlm.nih.gov/35050692/

A potential role for cannabichromene in modulating TRP channels during acute respiratory distress syndrome

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Special Issue Springer/Nature BMC Medical Informatics & Decision Making - Explainable-AI - human-centered.ai“Acute respiratory distress syndrome (ARDS) is a life-threatening clinical syndrome whose potential to become one of the most grievous challenges of the healthcare system evidenced by the COVID-19 pandemic. Considering the lack of target-specific treatment for ARDS, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve quality of life and outcomes for ARDS patients. ARDS is a systemic inflammatory disease starting with the pulmonary system and involves all other organs in a morbid bidirectional fashion. Mounting evidence including our findings supporting the notion that cannabinoids have potential to be targeted as regulatory therapeutic modalities in the treatment of inflammatory diseases. Therefore, it is plausible to test their capabilities as alternative therapies in the treatment of ARDS. In this study, we investigated the potential protective effects of cannabichromene (CBC) in an experimental model of ARDS.

Results: Our data showed that CBC was able to reverse the hypoxia (increasing blood O2 saturation by 8%), ameliorate the symptoms of ARDS (reducing the pro-inflammatory cytokines by 50% in lung and blood), and protect the lung tissues from further destruction. Further analysis showed that CBC may wield its protective effects through transient receptor potential (TRP) cation channels, TRPA1 and TRPV1, increasing their expression by 5-folds in lung tissues compared to sham and untreated mice, re-establishing the homeostasis and immune balance.

Conclusion: Our findings suggest that inhalant CBC may be an effective alternative therapeutic target in the treatment of ARDS. In addition, Increased expression of TRPs cation channels after CBC treatment proposes a novel role for TRPs (TRPA1 and TRPV2) as new potential mechanism to interpret the beneficial effects of CBC as well as other cannabinoids in the treatment of ARDS as well as other inflammatory diseases. Importantly, delivering CBC through an inhaler device is a translational model supporting the feasibility of trial with human subjects, authorizing further research.”

https://pubmed.ncbi.nlm.nih.gov/34598736/

“Cannabinoids are naturally occurring compounds in Cannabis plants. Numerous studies suggest beneficial effects of cannabinoids in clinical settings.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-021-00101-0

The potential of cannabinoids and inhibitors of endocannabinoid degradation in respiratory diseases

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European Journal of Pharmacology“The global incidence of respiratory diseases and complications is increasing. Therefore, new methods of treatment, as well as prevention, need to be investigated.

A group of compounds that should be considered for use in respiratory diseases is cannabinoids. There are three groups of cannabinoids – plant-derived phytocannabinoids, synthetic cannabinoids, and endogenous endocannabinoids including the enzymes responsible for their synthesis and degradation.

All cannabinoids exert their biological effects through either type 1 cannabinoid receptors (CB1) and/or type 2 cannabinoid receptors (CB2). In numerous studies (in vitro and in vivo), cannabinoids and inhibitors of endocannabinoid degradation have shown beneficial anti-inflammatory, antioxidant, anti-cancer, and anti-fibrotic properties.

Although in the respiratory system, most of the studies have focused on the positive properties of cannabinoids and inhibitors of endocannabinoid degradation. There are few research reports discussing the negative impact of these compounds. This review summarizes the properties and mechanisms of action of cannabinoids and inhibitors of endocannabinoid degradation in various models of respiratory diseases.

A short description of the effects selected cannabinoids have on the human respiratory system and their possible use in the fight against COVID-19 is also presented. Additionally, a brief summary is provided of cannabinoid receptors properties and their expression in the respiratory system and cells of the immune system.”

https://pubmed.ncbi.nlm.nih.gov/34648805/

“Phytocannabinoids are terpenophenolic compounds produced by specialized parts of the Cannabis sativa plant and are found in high concentrations in marijuana and hashish. In most of models, these compounds have shown positive biological properties. Anti-inflammatory, anti-oxidant, anti-cancer and anti-fibrotic actions are especially emphasized.”

https://www.sciencedirect.com/science/article/pii/S0014299921007160?via%3Dihub