# Evaluating the Metabolomic Profile and Anti-Pathogenic Properties of _Cannabis_ Species
## 3 Results and Discussion
### Antiviral Activity of Cannabis  
One of the recent research studies shows the possibility of _Cannabis_-derived compounds possessing antiviral properties with the potential to reduce morbidities and slow down the progression of various types of viral illnesses [123]. However, the antiviral properties of _Cannabis_ are the most understudied in modern medical research. Although _Cannabis_ has proven to synthesize a wide range of bioactive compounds, only cannabinoid compounds, particularly THC and CBD, appear to have been explored for their antiviral potential, and there exists insufficient knowledge on the antiviral action modes of cannabinoids on various types of viruses. According to [PERSON] et al. [124], CBD is known for its ability to induce apoptosis in mammalian cells and has been demonstrated to reduce extracellular vesicle release from HIV-infected monocytic cells and their viral cargo. [PERSON] et al. [125] assessed the antiviral effects of CBD in hepatitis B and hepatitis C and discovered that it was not active against HBV infection in vitro but exerted a cytotoxicity effect on the liver cell line, which was used to culture the virus. In another clinical trial, _Cannabis_ treatment was associated with lower levels of proinflammatory biomarkers in cerebral fluid (CSF) of HIV patients [126]; whereas, some studies reported that the treatment of Kaposi sarcoma-associated herpesvirus (KSHV) withvarious concentrations of CBD significantly reduced VEGFR-3 levels, suggesting another mechanism whereby CBD may affect the proliferation and viability of Kaposi sarcoma through the VEGFR-3 signaling pathway [127]. Similarly, in an HCV assay, CBD was reported to have successfully inhibited the virus by 84.5% with minimal cytotoxicity effect. Therefore, the direct antiviral activity of CBD towards HCV has demonstrated that the compound affects hepatitis, which is caused by activated T cells and macrophages as reported by [PERSON] et al. [125]. A previous research study by [PERSON] et al. [128] reported that the use of _Cannabis_ is related to a lower incidence of liver cirrhosis in chronic HCV patients. Further, longitudinal studies are still needed to ensure the effects of _Cannabis_ extracts and bioactive compounds to verify their effectiveness. Scientists have recently observed cannabinoids, especially THC and CBD, as possible drugs for SARS-CoV-2 [129]. Reviews and investigations on SARS-CoV-2 are currently dominating the research, resulting in fewer studies on some viruses or the possible re-emergence of other viruses. This is primarily due to empirical evidence revealing that cannabinoids such as CBD may be an efficient inhibitor of SARS-CoV-2 (strain 229E) replication in human lung fibroblasts (MRC-5) through enhancement of antiviral terpene efficacy [130]. In addition, cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA) have been proven to interact with the SARS-CoV-2 spike protein S1 subunit and prevent the entry of several live viral variants into human epithelial cells [131]. The mechanism of action of cannabinoids in SARS-CoV-2 inhibition has been reported to include inhibition of viral cell entry, inhibition of viral proteases, and stimulation of cellular innate immune responses [129]. There are also reports of CBD's ability to inhibit TMPRSS2 in several models of human epithelia. Additionally, CBD and THC, acting as CB2 receptor agonists, reduce the level of pro-inflammatory cytokines in lung cells [123]. Other recent studies have shown the ability of \(\Delta^{9}\)-THC to inhibit viral 3 CL pro caused by SARS-CoV-2 at IC50 3.62 \(\mu\)M [132] while others demonstrated a promising effect of \(\Delta^{9}\)-THCA-A in molecular modeling, thus, predicting inhibition of human angiotensin-converting enzyme 2 (ACE2) [133]. CBGA has been noted to bind orthosterically and allosterically to the SARS-CoV-2 spike protein S1 subunit (Kd = 5.6 \(\mu\)M) and prevent the cell entry of human epithelial and Vero cells by SARS-CoV-2 and early variants [131].