“The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global COVID-19 pandemic, challenging healthcare systems worldwide. Effective therapeutic strategies against this novel coronavirus remain limited, underscoring the urgent need for innovative approaches.

The present research investigates the potential of cannabis compounds as therapeutic agents against SARS-CoV-2 through their interaction with the virus’s papain-like protease (PLpro) protein, a crucial element in viral replication and immune evasion. Computational methods, including molecular docking and molecular dynamics (MD) simulations, were employed to screen cannabis compounds against PLpro and analyze their binding mechanisms and interaction patterns.

The results showed cannabinoids with binding affinities ranging from -6.1 kcal/mol to -4.6 kcal/mol, forming interactions with PLpro. Notably, Cannabigerolic and Cannabidiolic acids exhibited strong binding contacts with critical residues in PLpro’s active region, indicating their potential as viral replication inhibitors. MD simulations revealed the dynamic behavior of cannabinoid-PLpro complexes, highlighting stable binding conformations and conformational changes over time.

These findings shed light on the mechanisms underlying cannabis interaction with SARS-CoV-2 PLpro, aiding in the rational design of antiviral therapies. Future research will focus on experimental validation, optimizing binding affinity and selectivity, and preclinical assessments to develop effective treatments against COVID-19.”

https://pubmed.ncbi.nlm.nih.gov/38932170/

“In summary, targeting PLpro with cannabinoids offers a promising approach for inhibiting viral replication, attenuating pathogenicity, and enhancing therapeutic outcomes in the fight against COVID-19 and other viral infections.”

https://www.mdpi.com/1999-4915/16/6/878

“The search for new active substances against SARS-CoV-2 is still a central challenge after the COVID-19 pandemic. Antiviral agents to complement vaccination are an important pillar in the clinical situation.

Selected cannabinoids such as cannabigerol, cannabicyclol, cannabichromene, and cannabicitran from Cannabis sativa and synthetic homologues of cannabigerol and cannabicyclol were evaluated for effects on the cell viability of Vero cells (CC₅₀ of cannabigerol and cannabicyclol 40 resp. 38 µM) and reduced virus entry of vesicular stomatitis pseudotyped viruses with surface-expressed SARS-CoV-2 spike protein at 20 µM. In addition to a reduction of pseudotyped virus entry, a titer reduction assay on Vero cells after preincubation of Wuhan SARS-CoV-2 significantly confirmed antiviral activity.

Investigations on the molecular targets addressed by cannabigerol and cannabicyclol indicated that both compounds are inhibitors of SARS-CoV-2 spike protein-mediated membrane fusion, as could be shown by a virus-free reporter fusion inhibition assay (EC₅₀ for cannabigerol 5.5 µM and for cannabicyclol 10.8 µM) and by monitoring syncytia formation in Vero reporter cells. Selectivity indices were calculated as 7.4 for cannabigerol and 3.5 for cannabicyclol. Systematic semisynthetic alterations of cannabigerol and cannabicyclol indicated that the side chains of both compounds do not contribute to the observed anti-membrane fusion activity.”

https://pubmed.ncbi.nlm.nih.gov/38885660/

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-2320-8822

“Background: Since the COVID-19 outbreak in early 2020, researchers and studies are continuing to find drugs and/or vaccines against the disease. As shown before, medicinal plants can be very good sources against viruses because of their secondary compounds which may cure diseases and help in survival of patients. There is a growing trend in the filed patents in this field.

Aims: In the present study, we test and suggest the inhibitory potential of five herbal based extracts including 7α-acetoxyroyleanone, Curzerene, Incensole, Harmaline, and Cannabidiol with antivirus activity on the models of the significant antiviral targets for COVID-19 like spike glycoprotein, Papain-like protease (PLpro), non-structural protein 15 (NSP15), RNA-dependent RNA polymerase and core protease by molecular docking study.

Methods: The Salvia rythida root was extracted, dried, and pulverized by a milling machine. The aqueous phase and the dichloromethane phase of the root extractive were separated by two-phase extraction using a separatory funnel. The separation was performed using the column chromatography method. The model of the important antivirus drug target of COVID-19 was obtained from the Protein Data Bank (PDB) and modified. TO study the binding difference between the studied molecules, the docking study was performed.

Results: These herbal compounds are extracted from Salvia rhytidea, Curcuma zeodaria, Frankincense, Peganum harmala, and Cannabis herbs, respectively. The binding energies of all compounds on COVID-19 main targets are located in the limited area of 2.22-5.30 kcal/mol. This range of binding energies can support our hypothesis for the presence of the inhibitory effects of the secondary metabolites of mentioned structures on COVID-19. Generally, among the investigated herbal structures, Cannabidiol and 7α- acetoxyroyleanone compounds with the highest binding energy have the most inhibitory potential. The least inhibitory effects are related to the Curzerene and Incensole structures by the lowest binding affinity.

Conclusion: The general arrangement of the basis of the potential barrier of binding energies is in the order below: Cannabidiol > 7α-acetoxyroyleanone > Harmaline> Incensole > Curzerene. Finally, the range of docking scores for investigated herbal compounds on the mentioned targets indicates that the probably inhibitory effects on these targets obey the following order: main protease> RNA-dependent RNA polymerase> PLpro> NSP15> spike glycoprotein.”

https://pubmed.ncbi.nlm.nih.gov/38817009/

https://www.eurekaselect.com/article/136307

“Aims: To conduct a single arm open-label feasibility trial of the safety and tolerability of a full-spectrum cannabidiol (CBD)-dominant cannabis-based medicinal product (CBMP) for treating the symptoms of Long COVID.

Methods: The treatment phase ran for a total of 21 weeks, followed by ~3 weeks without the study drug. Participants received up to 3 mL of MediCabilis 5% CBD Oil (50 mg CBD/mL, <2 mg delta-9-tetrahydrocannabinol (THC)/mL) per day orally. Monthly patient reported outcome measures (PROMs) of common symptoms and daily self-report of symptoms were collected via a smartphone app. Key measures of heart rate, activity, sleep, and oxygen saturation were assessed using wearable technology.

Results: 12 (1 male, 11 female) individuals diagnosed with Long COVID were recruited into the trial. All patients adhered to the treatment protocol for the duration of the study and there were no serious adverse events. Response rates for the research assessments were high with over 90% completion of PROMs and daily self-report.

Conclusion: The study drug was safe and well tolerated, demonstrating feasibility of CBD-dominant CBMPs in individuals diagnosed with Long COVID. However, there were limitations in research design related to recruitment strategy demonstrating a lack of feasibility in the approach implemented in this study. Future work with larger samples and incorporating a control group are required to test the efficacy of this treatment.”

https://pubmed.ncbi.nlm.nih.gov/38105651/

https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15988