A method of use for cannabidiol in the prevention and treatment of interferon-responsive conditions

Abstract

The invention relates to Cannabidiol or compositions of Cannabidiol for use in the treatment of infections caused by pathogens and parasites. The invention relates to use of Cannabidiol or compositions of Cannabidiol for the treatment of infections caused by pathogens, particularly those pathogens which are likely to activate either cGAS-STING pathway or 2',5'-oligoadenylate synthetase (OAS)-RNase L pathway. The invention relates to Cannabidiol or compositions of Cannabidiol for use in the prevention of infections / prophylaxis or priming animal or host for better preparing for infections.

Description

[0001] A method of use for cannabidiol in the prevention and treatment of interferon- responsive conditions Field of the Invention The invention relates to Cannabidiol or compositions of Cannabidiol for use in the treatment of infections caused by pathogens and parasites. The invention relates to use of Cannabidiol or compositions of Cannabidiol for the treatment of infections caused by pathogens, particularly those pathogens which are likely to activate either cGAS-STING pathway or 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway. The invention relates to Cannabidiol or compositions of Cannabidiol for use in the prevention of infections / prophylaxis or priming animal or host for better preparing for infections. The invention relates to use of Cannabidiol or its compositions in treating several infections by enhancing innate immunity of animal or host where administration of Cannabidiol or its compositions cause induction of interferons and their downstream effectors which plays a key role in eliminating several pathogens and parasites. Cannabidiol or its compositions cause upregulation of several interferons and / or their downstream effectors and cause apoptosis. This can be of immense importance not only in treatment but also in prevention, priming (preparing for attack) against various pathogens. The host cells are better able to prepare for infection including increase in the infectious dose. Thus, the inventors had demonstrated and proposed that the pathogens and parasites in elimination of which interferons and their downstream effectors and / or play a key role can be eliminated by administration of one or more Cannabinoids. Background of the invention Ma Z, and Damania B. mention that numerous DNA viruses have been reported to activate the cGAS–STING pathway, and cGAS or STING deficient mice are more susceptible to lethal infection after exposure to many DNA viruses, including herpes simplex virus 1 (HSV-1), vaccinia virus, and murine gammaherpesvirus 68 (MHV68). Infection of retroviruses such as human immunodeficiency virus (HIV) generates RNA:DNA hybrids and dsDNA in the cytosol that can also activate the cGAS– STING pathway (Gao D et al, 2013; and Mankan AK et al, 2014) Ni G et al reports that emerging evidence indicates that, in addition to its well- established role in sensing cytosolic DNA, the cGAS–STING pathway is also involved in restricting RNA virus infection, suggesting that there exists crosstalk between the innate sensing of cytosolic DNA and RNA. cGAS binds to cytosolic double-stranded DNA (dsDNA) from various sources, including bacteria, DNA viruses, and retroviruses, in a sequence-independent but length-dependent manner (Wu J and Chen ZJ. , 2014 and Andreeva L et al, 2017) All above studies point out to the fact that cGAS – STING activation by cytosolic DNA or RNA produces host immune response. The present invention further investigates if cGAS – STING activation can be augmented and whether such augmentation can be used in the treatment of infections caused by pathogens and parasites. Roles of Interferons and Interferon-stimulated gene (ISG) products at resisting and controlling pathogens has been reported. The interferon responsive conditions also include in addition to treatment or prevention or priming against infectious diseases, treatment for one or more cancers and for autoimmune diseases. Schneider WM et al provides diverse roles of Interferons and Interferon-stimulated gene (ISG) products at resisting and controlling pathogens and roles of Type I IFNs and IFNARs, Type II IFN and IFNGR, Type III IFN, IL-10, and IFNLR, Interferon induced antiviral effectors including Mx1, Mx2, Cholesterol-25-hydroxylase, Oxysterols, IFITM proteins, TRIM proteins (The tripartite motif (TRIM) family of proteins), ISGs including zinc-finger antiviral protein (ZAP), the IFN-induced protein with tetratricopeptide repeats (IFIT) family, the OAS-RNaseL pathway, and Protein Kinase R (PKR). Samantha L. Schwartz and Graeme L. Conn (Schwartz and Conn, 2019) report role and nature of defense by OAS family of enzymes as important sensors of cytosolic double-stranded RNA (dsRNA) that play a critical role in limiting viral infection by activating the latent ribonuclease L (RNase L) to halt viral replication and establish an antiviral state. Yize Li et al (Yize Li et al, 2016 Abstract) reports as follows: “The 2',5'-oligoadenylate (2-5A) synthetase (OAS)-RNase L system is an IFN- induced antiviral pathway. RNase L activity depends on 2-5A, synthesized by OAS. Although all three enzymatically active OAS proteins in humans--OAS1, OAS2, and OAS3--synthesize 2-5A upon binding dsRNA, it is unclear which are responsible for RNase L activation during viral infection.” Kulka M et al. (Kulka M et al., 2009) in their article “Activation of the 2- 5OAS / RNase L pathway in CVB1 or HAV / 18f infected FRhK-4 cells does not require induction of OAS1 or OAS2 expression” states as follows: “Most importantly, these results suggest that constitutive levels of OAS, in particular OAS3, may be sufficient for synthesis of 2-5A and activation of RNase L in FRhK-4 cells during virus infection, although not all virus infections (e.g.,HAV / HM175 clone 1) will trigger this response. Our results suggest a need for further investigation into picornavirus replication / dsRNA formation and OAS3 activation in FRhK-4 cells compared to other monkey and human kidney cell lines.” Thus, Kulka M et al. made an important observation that not all virus infection can cause synthesis of 2-5A (2',5'-oligoadenylate) and activation of RNase L during virus infection. Thus, there are certain infections where host cells cannot produce sufficient amounts of OAS which are required for activation of RNase L which can limit viral replication. Interestingly through research of various researchers it has been noted that in any infection almost always host cells put up their own defense by inducing one or more interferons and interferons’ downstream effectors against pathogens. Sometimes the amounts of interferons induced, or induction of their downstream effectors are not sufficient. Therefore, the host cell can succumb to viral attack. As in case of SARS-Cov-2 virus, host cells often succumb to the viral attack. However, certain other times it is observed that host cells put up defense by substantial production of interferons and their down-stream effectors, which can stop the cells from becoming infected, or allow cells to clear virus that enters the cells or prevent the infecting virus from replicating inside of a cell. Preventing replication by a pathogen with a nucleic acid genome (i.e. RNA or DNA-based viruses, bacteria, parasites, fungal infections, mycobacteria, etc), is particularly important for host health and survival, and population health and survival, since replication by intracellular pathogens is needed in order for the pathogen to spread within the host, or from the host to other hosts, and it is also needed for a pathogen to form variants that may be more infectious, or resistant to treatment. Sirui Zhou et al (Sirui Zhou et al, 2020) in the article “Circulating Proteins Influencing COVID-19 Susceptibility and Severity: a Mendelian Randomization Study” reports that proteins detectable in peripheral blood may influence COVID- 19 susceptibility or severity. Levels of four circulating proteins, 2'-5'- oligoadenylate synthetase 1 (OAS1), interleukin-10 receptor beta subunit (IL10RB), ABO, and liposaccharide binding protein (LBP) were studied in context of one or more COVID-19 outcomes such as susceptibility, hospitalization and severity. Figure 1 provides result of “Association of Circulating Protein Levels with COVID-19 Outcomes”. The study concludes (abstract) as follows: “We found that a standard deviation increase in OAS1 levels was associated with reduced COVID-19 death or ventilation (N = 2,972 cases / 284,472 controls; OR = 0.48, P = 7x10-8), COVID-19 hospitalization (N = 6,492 / 1,012,809; OR = 0.60, P = 2x10-7) and COVID-19 susceptibility (N = 17,607 / 1,345,334; OR = 0.81, P = 6x10-5). Results were consistent despite multiple sensitivity analyses probing MR assumptions. OAS1 is an interferon-stimulated gene that promotes viral RNA degradation. Other potentially implicated proteins included IL10RB. Available medicines, such as interferon-beta-1b, increase OAS1 and could be explored for their effect on COVID-19 susceptibility and severity.” Interferons play roles in controlling infections by parasites. Some of the examples are as follows. SH Ferguson and colleagues have found that IFN ^3 promotes epithelial defense and barrier function against the intestinal parasite Cryptosporidium parvum infection, and that “Immunoneutralization of IFN-λ2 / 3 in C parvum-infected neonatal mice resulted in a significantly increased parasite burden, fecal shedding, and villus blunting with crypt hyperplasia during peak infection. Priming of intestinal epithelial cells with recombinant human IFN-λ3 promoted cellular defense against C parvum infection and abrogated C parvum-induced loss of barrier function. T Melzer and colleagues write that “Gamma interferon (IFN-gamma) is the main cytokine mediating protection against a protozoan Toxicoplasmosis gondii, which is a common infection of the central nervous system in immunocompromised individuals. Olmo Pinheiro and Rossi-Bergmann write that “The critical role of interferon- gamma (IFN-gamma) in the resistance of C57Bl / 6 mice to Leishmania major is widely established” and find that Interferon-gamma is required for the late but not early control of Leishmania amazonensis infection in C57Bl / 6 mice. MB McCall and RW Sauerwein conclude that IFN-γ forms a central mediator of protective immune responses against pre-erythrocytic and blood-stage malaria parasites. It has been well established that IFN-γ has protective function against M. tuberculosis and the other mycobacteria. (Travar M,et al, 2016). According to Smith and Denning: “Interferon-γ is key in the immune response to M. tuberculosis. Interferon-γ production following recognition of this pathogen is important in macrophage activation and phagocytosis and results in inhibition of growth and death of the mycobacteria. Reduced IFN-γ production, and the resulting reduced Th1 response has been particularly associated with TB, and levels of IFN- γ and IL-12 increase during anti-TB treatment”. In addition, adjuvant therapy with IFN-γ may be beneficial in TB patients (Smith and Denning, 2014). Tuberculosis had been associated with mutations in the IFN-γ gene in many different ethnic groups (Ding S et al, 2008; Cooke GS et al, 2006; Lio Det al, 2002; Shen C et al, 2013; Ansari A et al, 2011; Vallinoto AC et al, 2010; Tso HW et al, 2005). Reduced IFN-γ production and reduced Th1 responses have also been observed in non-tuberculosis mycobacterial infections such as those caused by Mycobacterium malmoense or Mycobacterium avium (Sahrbacher U et al, 2007; Vankayalapati Ret al, 2001). Genetic associations with the IFN-γ gene have not yet been identified in these groups; however, associations with the IFN-γ receptor have been described, as have associations with anti-IFN-γ antibodies (Storgaard M et al, 2006).” Interferon lambdas also help control bacterial infections by Staphylococcus aureus and Mycobacterium tuberculosis (Syedbasha M et al, 2017). IFN ^1 can inhibit the colonization of S. aureus in human primary keratinocytes (Wu X et al, 2021) , and enhance the clearance of S. aureus in healthy nasal mucosa (Lan F et al, 2019). Smith and Denning wrote: ‘In addition to a role in bacterial infections, IFN-γ may also be important in defence against fungal infections. Cryptococcosis is usually caused by Cryptococcus neoformans, occasionally by Cryptococcus gattii, the latter notably in non-immunocompromised patients (Chen SC, et al, 2013). Following inhalation, the usual manifestation of disease is meningitis, although pneumonia (Harris JR et al, 2012) and other forms of disseminated cryptococcosis, notably skin and bone disease, also occur. Patients who fail to mount a directed IFN-γ response in cryptococcal meningitis are much more likely to die than those who do, irrespective of antifungal therapy (Jarvis JN et al, 2013). “. In Aspergillus-induced fungal lung disease, low levels of IFN ^ are associated with progressive chronic pulmonary aspergillosis, and treatment with recombinant IFN ^ has been found to cause significant clinical improvement (Kelleher P et al, 2006). Additional threat in infection is that many types of bacterial, viral and parasitic infections have a potential to become latent, with a capacity for reactivation that can cause significant morbidity and mortality. Type I interferons, and particularly IFN-alpha, play a role in limiting acute HIV infection, and NM Bourke and colleagues suggest that it may be important in devising a therapy to eliminate latent HIV reservoirs (Bourke NM et al, 2018). IFN-gamma is important for controlling replication of Toxoplasma gondii (Ghaffarifar F et al, 2006) and is implicated in preventing the development of toxoplasmic encephalitis during chronic infection (Wen X et al, 2010). Persistent latent viral infections are associated with the etiology and pathogenesis of multiple sclerosis. J Hong and colleagues found that administration of IFN-beta to patients with multiple sclerosis reduced the replication of human herpesvirus-6 (HHV-6), a latent neurotropic virus, in a T-cell line. Treatment of patients reduced IgM reactivity to HHV-6, indicating reduced exposure in vivo after treatment with IFN-beta. This suggests that therapies that raise IFN-beta levels may therefore be of benefit for treating primary latent infections, and also comorbidities associated with infection, such as multiple sclerosis. (Hong J et al, 2002). IFN-gamma release is assayed as a marker of latent tuberculosis infection, indicating that host defence from this pathogen involves INF-gamma (Pai M et al, 2016). Both patients and physicians are reported to perceive the risk of toxicity from treatment of latent tuberculosis infection with isoniazid to be greater than the risk of reactivation TB (Chee CBE et al, 2018). In latent / persistent cases, the infecting pathogen persists in the body long after symptoms resolve and can cause disease later in life. One such example where Cannabidiol is found effective is for treating infection by Sars-Cov-2 which can lead to Long Covid. Since Interferon-gamma may have an application for the late control of Leishmania amazonensis infection and since Cannabinoids cause induction of Interferon-gamma, they can be employed for treating long term infection by this parasite. One more threat to mankind is existence of multiple infections. Harris JR et al reports a high prevalence of cryptococcal infection among HIV-infected patients hospitalized with pneumonia in Thailand (Harris JR et al, 2012). Interestingly, over recent years considerable research is focussed on role of various Interferons in cancers and autoimmune diseases. IFN-α2 was the first cancer immunotherapy approved by the US Food and Drug Administration. IFN ^ gene therapy has been proposed for the treatment of cancer (Yoshida J et al, 2004) IFN ^ plays a pivotal role in the effectiveness of ionizing radiation as an anti-tumor therapy (Gerber SA et al, 2013) IFN ^ also inhibits the growth of a variety of different types of cancer cells including breast cancer (Kochupurakkal Best al, 2015), colorectal cancer (Wang L,et al, 2015), and hepatocellular cancer (Li Wet al, 2012) . Interferon-mediated responses are also important in offering protection to an organism from tumor growth and invasion and, indeed, an IFN-alpha-based drug was the first immunotherapy approved for cancer treatment by the US Food and Drug Administration (Stiff and Carson III, 2015). Zhang F et al states that Type I IFNs are an integral component of the early innate immune response and play an important role in anti-tumor immunity. (Zhang F et al, 2020) Andrew Stiff and William Carson III report that Interferon-lambda (IFN-λ), a recently discovered cytokine, overlaps broadly with type I IFN signaling, producing antiviral, antiproliferative, and proapoptotic responses. According to them, IFN-λ can also potentially alter the balance between Th1 and Th2 immune responses, which may be able to be taken advantage of for the treatment of cancer. They conclude that the ability of IFN-λ to inhibit the development of potentially protumor Th2 immune responses in favor of antitumor Th1 responses suggests it would be interesting to evaluate the efficacy of IFN-λ in combination with emerging immunotherapeutic approaches. Gerber SA et al states as follows: “Our report makes a significant contribution to understanding the mechanism of how the consequential immune response following radiotherapy mediates tumor control. In particular, we demonstrated that the Th1 cytokine, IFN-γ, which was predominantly produced by i.t. CD8+ T cells, was essential to elicit the antitumor effects of radiation. This is particularly interesting because recent reports suggest that IFN-γ may be detrimental to tumor control.” A. Stiff and W. Carson write that “To date, a number of studies using both murine and human models of cancer have investigated the antitumor effects of IFN-λ. These studies have found that IFN-λ is capable of directly targeting cancer cells to reduce their tumorigenicity, induce cell cycle arrest, and cause apoptosis. In addition, IFN-λ has been shown to have indirect effects against cancer cells through immune system responses and immune modulatory effects.” Additionally, interferon-mediated regulation plays complex roles in autoimmunity. While some interferon types may have a detrimental role in some autoimmune disease, evidence suggests a potential protective role for Lambda-type interferons in inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis (Vlachiotis S et al, 2019). Thus, cGAS-STING pathway and 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway are two promising pathways which are activated during infection to boost innate immune response.The present invention investigates whether the above pathways can be further augmented and whether such augmentation can be used in the treatment of infections caused by pathogens and parasites. If such augmentation can be produced, it would hold immense potential in treatment of any infection caused by DNA type virus, RNA type Virus, bacteria including M. tuberculosis, fungi, protozoa and other parasites. Summary of the Invention In the first aspect, the invention provides pharmaceutical composition comprising therapeutically effective amount of Cannabidiol for use in treating an infection in a host / patient. Cannabidiol or its composition produces an enhancement / augmentation of innate immunity of the host / patient against said infection after activation of either cGAS-STING pathway or 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway or both of these pathways. Once one of these pathways is activated, there is an enhancement / augmentation of innate immunity of the host / patient against said infection by one or more of the following: a) augmenting induction of interferons; b) augmenting induction of interferon stimulated factors or genes; c) by causing apoptosis of virus infected cells. In the second aspect, pharmaceutical composition comprising therapeutically effective amount of Cannabidiol for use in preventing an infection in a host / patient or for use in priming / preparing a host / patient for infection are provided. In the third aspect, method of treating an infection in a host / patient by administering the above described compositions are provided. In the fourth aspect, method of preventing an infection in a host / patient or method of priming / preparing a host / patient for infection comprising administering pharmaceutical composition comprising therapeutically effective amount of Cannabidiol are provided.

[0002] Brief Description of Drawings Figures 1A to 1G provide images of glowing HEK-293 cells with various concentrations of Cannabidiol such as 0, 0.5, 1, 1.5, 2, 2.5,3 µM and infected with adenovirus at a multiplicity of infection = 1, after 48 hours. Figure 2 provides a plot of the number of glowing cells per field of view at 4x magnification at different concentrations of Cannabidiol, 48 hours after infection with adenovirus at a multiplicity of infection =1. Figure 2 shows that the number of glowing cells per field is significantly less when cells are treated with 0.5 µM Cannabidiol, and this effect is even greater when cells are treated with 1 µM Cannabidiol or higher concentrations of Cannabidiol. Figure 3A provides a plot of the total number of live cells (counted using the Cytation 5 in brightfield mode) per field at 4x magnification at various concentrations of Cannabidiol viz.0.5, 1.0, 1.5, 2.0, 2.5, 3.0 µM CBD, or vehicle alone (0 µM CBD), 48 hours after infection with adenovirus at a multiplicity of infection =1. Figure 3B provides a plot of the percentage of GFP-positive (or infected) cells treated at various concentrations of Cannabidiol viz.0.5, 1.0, 1.5, 2.0, 2.5, 3.0 µM CBD, or vehicle alone (0 µM CBD), 48 hours after infection with adenovirus at a multiplicity of infection =1. Figure 3B shows that the percentage of glowing cells per field is significantly less when cells are treated with 0.5 µM Cannabidiol, and this effect is even greater when cells are treated with 1 µM Cannabidiol or higher concentrations of Cannabidiol. Figures 4A and 4B respectively provide a measurement of early and late apoptosis indexes 24 hours after infection with adenovirus at a multiplicity of infection =1. Figures 4A and 4B show that 1 µM Cannabidiol does not increase the early or late apoptosis index when adenovirus is not present, and that adenovirus alone does not increase the early or late apoptosis index when CBD is not present. Figure 4A and 4B show that adding 1 µM Cannabidiol to cells infected with adenovirus significantly increases the early and late apoptosis indexes compared to cells that are not infected, or that are infected but not treated with 1 µM Cannabidiol. Figures 5A provides gene expression of IFN ^ when host cells uninfected and infected with Adenovirus are treated with 1 µM Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol), after 48 hours. Treatment of infected or uninfected cells with 1 µM Cannabidiol for 48 hours significantly increased IFN ^ expression, but IFN ^ expression was highest in cells infected with adenovirus and treated with 1 µM Cannabidiol. Figures 5B provides gene expression of IFNβ when host cells uninfected and infected with Adenovirus are treated with Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol) after 48 hours. Treatment of infected or uninfected cells with 1 µM Cannabidiol significantly increased IFNβ expression, but IFNβ expression was highest in cells infected with adenovirus and treated with 1 µM Cannabidiol. Figures 5C provides gene expression of IFNγ when host cells uninfected and infected with Adenovirus are treated with Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol) after 48 hours. Treatment of infected or uninfected cells with 1 µM Cannabidiol significantly increased IFNγ expression, but IFNγ expression was highest in cells infected with adenovirus and treated with 1 µM Cannabidiol. Figures 5D provides gene expression of IFN ^1 when host cells uninfected and infected with Adenovirus are treated with Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol) after 48 hours. Treatment of infected or uninfected cells with 1 µM Cannabidiol significantly increased IFN ^1 expression, but IFN ^1 expression was highest in cells infected with adenovirus and treated with 1 µM Cannabidiol. Figures 5E provides gene expression of IFN ^2,3 when host cells uninfected and infected with Adenovirus are treated with Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol) for 48 hours. Treatment of infected or uninfected cells with 1 µM Cannabidiol significantly increased IFN ^2,3 expression, but IFN ^2,3 expression was highest in cells infected with adenovirus and treated with 1 µM Cannabidiol. Figures 5F provides gene expression of Mx1 when host cells uninfected and infected with Adenovirus are treated with Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol) for 48 hours. Figure 5F shows that treatment of adenovirus-infected cells with 1 µM Cannabidiol increases expression of Mx1 compared to cells that are not infected with adenovirus and not treated with Cannabidiol. Figures 5G provides gene expression of iFit when host cells uninfected and infected with Adenovirus are treated with Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol) for 48 hours. Treatment of infected or uninfected cells with 1 µM Cannabidiol significantly increased iFit expression, but iFit expression was highest in cells infected with adenovirus and treated with 1 µM Cannabidiol. Figures 5H provides gene expression of OAS1 when host cells uninfected and infected with Adenovirus are treated with Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol) for 48 hours. Treatment of infected or uninfected cells with 1 µM Cannabidiol significantly increased OAS1 expression, but OAS1 expression was highest in cells infected with adenovirus and treated with 1 µM Cannabidiol. Figures 5I provides gene expression of OAS2 when host cells uninfected and infected with Adenovirus are treated with Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol) for 48 hours. Treatment of infected or uninfected cells with 1 µM Cannabidiol significantly increased OAS2 expression, but OAS2 expression was highest in cells infected with adenovirus and treated with 1 µM Cannabidiol. Figures 5J provides gene expression of OAS3 when host cells uninfected and infected with Adenovirus are treated with Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol) for 48 hours. Treatment of infected or uninfected cells with 1 µM Cannabidiol significantly increased OAS3 expression relative to treatment with vehicle alone. Figures 5K provides gene expression of OASL when host cells uninfected and infected with Adenovirus are treated with Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol) for 48 hours. Treatment of infected or uninfected cells with 1 µM Cannabidiol significantly increased OASL expression, but OASL expression was highest in cells infected with adenovirus and treated with 1 µM Cannabidiol. Figure 6A provides total levels of cGAS protein in a Western immunoblot. The red arrow denotes the band corresponding to the cGAS protein. The method is described under example section. Figure 6B is a loading-control image, that corresponds to the blot in Figure 6A. This figure shows total protein levels in each of the lanes. After electrophoresing total cellular protein lysates in an SDS-PAGE gel, total proteins in each lane were detected by imaging the gel under a UV light. The gels that are used are called ‘Stain-FreeTM’ gels, and will allow proteins to fluoresce under ultraviolet light, for easy measure of total protein content. Figure 6C - This graph shows the total content of cyclic GMP-AMP Synthase (cGAS), normalized to total protein content per lane, from n=4 separate biological samples. There was no significant effect of adenovirus infection compared to uninfected (i.e. mock infected) cells, and no significant effect of CBD, either alone or in combination with adenovirus on total cGAS levels. Figure 7A summarizes the quantitative findings from the blots below in Figures 7B and 7C. This graph shows that the total level of Stimulator of Interferon Genes (STING) protein, normalized to total protein content per lane, and expressed as a percent of mock-infected cells treated only with vehicle (not with CBD), does not change significantly when cells are infected with adenovirus, whether or not they are treated with CBD. Figures 7B and 7C - These blots show immunodetectable levels of total STING protein, as well as Stain-FreeTMgel images, showing total loading per lane (below the main image). Figure 8A - The graph summarizes the quantitative findings from the blots below in Figures 8B and 8C. This graph shows that the level of STING phosphorylated at serine 366 (P-STING) protein, normalized to total protein content per lane, and expressed as a percent of mock infected cells treated only with vehicle (not with CBD), is significantly reduced when cells are infected with adenovirus, but treatment with CBD reverses this effect (CBD stops adenovirus from being able to down-regulate P-STING). Figures 8B and 8C - The blots provided in figures 8B and 8C show immunodetectable levels of P- STING protein, as well as Stain-FreeTMgel images, showing total loading per lane (below the main image) as a control. Figure 9A summarizes the quantitative findings from the blots below in Figures 9B and 9C. This graph shows that the level of total Tank-binding kinase 1 (TBK1) protein (also called NAK), normalized to total protein content per lane (based on stain-free gel imaging), is significantly reduced when cells are infected with adenovirus, but treatment with CBD reverses this effect (CBD stops adenovirus from being able to down-regulate total TBK1). Figures 9B and 9C - These blots show immunodetectable levels of total TBK1 protein, as well as Stain-FreeTMgel images, showing total loading per lane (below the main image) as a control. NAK is another name for TBK1, so it is also listed on these blots. Figure 10A summarizes the quantitative findings from the blots shown in figures 10B and 10C. This graph shows that the level of TBK1 protein phosphorylated at serine 172 (P-TBK1), normalized to total protein content per lane (based on Stain- FreeTMgel imaging), is significantly reduced when cells are infected with adenovirus, but treatment with CBD reverses this effect (CBD stops adenovirus from being able to downregulate levels of P-TBK1). Figures 10B and 10C show immunodetectable levels of total TBK1 protein, as well as Stain-FreeTMgel images, showing total protein loading per lane (below the main image) as a control. NAK is another name for TBK1, so it is also listed on these blots. Figure 11 provides a graph which shows the relative number of GFP positive cells 48 hours after all cells were infected with Adenovirus at a multiplicity of infection =1 and treated with 1 ^M Cannabidiol or vehicle control (0.1% ethanol (EtOH) with or without the STING inhibitor RU-521 (0.8 ^M) (expressed as a percentage of the control well, where cells were infected with adenovirus, but not treated with CBD or with RU-521, but instead only received the vehicle controls for those substances). Figure 12 provides a graph which shows the relative number of GFP positive cells 48 hours after all cells were infected with Adenovirus at a multiplicity of infection =1 and treated with 1 ^M Cannabidiol or vehicle control (0.1% ethanol (EtOH) with or without the cGAS inhibitor H-151 (1 ^M) (expressed as a percentage of the control well, where cells were infected with adenovirus, but not treated with CBD or with H-151, but instead only received the vehicle controls for those substances). Figure 13 shows quantification of the relative level of adenovirus hexon DNA relative to mouse chromosomal 18s DNA detected in livers of mice 2-days, 4-days, and 6-days after mice were infected by injection in the retro-orbital vein with 2 x 108infectious units of serotype 5 Adenovirus. Prior to infection, mice were gavaged with 80 mg / kg Cannabidiol dissolved in sesame oil once daily for 3-days (CBD) or given sesame oil alone (vehicle), and mice continued to receive this treatment after infection until euthanasia. Figure 14 shows quantification of the relative level of adenovirus hexon DNA detected in mouse liver relative to quantification of a mouse chromosomal gene (exon 1 of Pnpla2). This figure provides another analysis of the hexon data, relative to a different mouse chromosomal gene. It serves to provide an additional analysis validating approach of inventors with 18s. Figures 15A provides gene expression of IFN ^ when host cells uninfected and infected with Lentivirus are treated with 1 µM Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol), after 24 hours. Treatment of infected cells with 1 µM Cannabidiol for 24 hours significantly increased IFN ^ expression. IFN ^ expression was highest in cells infected with adenovirus and treated with 1 µM Cannabidiol. Figure 15B-15C show gene expression of INF ^ in HEK293 cells infected with lentivirus, and treated with or without 1 ^M CBD, and with or without the cGAS inhibitor RU-521 (0.8 ^M), or with and without the STING inhibitor H-151 (1 ^M). Figures 15B-15C demonstrate that cGAS inhibition or STING inhibition prevents Cannabidiol-mediated augmentation of INF ^ gene expression, and therefore cGAS-STING pathway signaling is needed for Cannabidiol to increase INF ^ gene expression. Figures 16A provides gene expression of IFNβ when host cells uninfected and infected with Lentivirus are treated with Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol) after 24 hours. Treatment of infected cells with 1 µM Cannabidiol significantly increased IFNβ expression, and IFNβ expression was highest in cells infected with adenovirus and treated with 1 µM Cannabidiol. Figures 16B- 16C show gene expression of INF ^ in HEK293 cells infected with lentivirus, and treated with or without 1 uM CBD, and with or without the cGAS inhibitor RU-521 (0.8 µM), or with and without the STING inhibitor H-151 (1 µM). Figures 16B-15C demonstrate that cGAS inhibition or STING inhibition prevents Cannabidiol-mediated augmentation of INFβ gene expression, and therefore cGAS- STING pathway signaling is needed for Cannabidiol to increase INF ^ gene expression. Figures 17A provides gene expression of IFNγ when host cells uninfected and infected with Lentivirus are treated with Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol) after 24 hours. IFNγ expression was higher in cells infected with adenovirus and treated with 1 µM Cannabidiol than in uninfected cells. Figures 17B- 17C show gene expression of INFγ in HEK293 cells infected with lentivirus, and treated with or without 1 µM CBD, and with or without the cGAS inhibitor RU-521 (0.8 µM), or with and without the STING inhibitor H-151 (1 µM). Figures 17B-17C demonstrate that cGAS inhibition or STING inhibition prevents Cannabidiol-mediated augmentation of INFγ gene expression, and therefore cGAS- STING pathway signaling is needed for Cannabidiol to increase INFγ gene expression. Figures 18A provides gene expression of IFN ^1 when host cells uninfected and infected with Lentivirus are treated with Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol) after 24 hours. Treatment of infected cells with 1 µM Cannabidiol significantly increased IFN ^1 expression. IFN ^1 expression was highest in cells infected with adenovirus and treated with 1 µM Cannabidiol. Figures 18B-18C show gene expression of IFN ^1 in HEK293 cells infected with lentivirus, and treated with or without 1 µM CBD, and with or without the cGAS inhibitor RU-521 (0.8 µM), or with and without the STING inhibitor H-1511 µM). Figures 18B-18C demonstrate that cGAS inhibition or STING inhibition prevents Cannabidiol-mediated augmentation of IFN ^1 gene expression, and therefore cGAS-STING pathway signaling is needed for Cannabidiol to increase INF ^1 gene expression. Figures 19A provides gene expression of IFN ^2 / 3 when host cells uninfected and infected with Lentivirus are treated with Cannabidiol relative to treatment with vehicle alone (i.e., without Cannabidiol) after 24 hours. Treatment of infected cells with 1 µM Cannabidiol significantly increased IFN ^2 / 3 expression. IFN ^2 / 3 expression was highest in cells infected with adenovirus and treated with 1 µM Cannabidiol. Figures 19B- 19C show gene expression of INFλ2 / 3 in HEK293 cells infected with lentivirus, and treated with or without 1 uM CBD, and with or without the cGAS inhibitor RU-521 (0.8 µM ), or with and without the STING inhibitor H-151 (1 µM). Figures 19B-19C demonstrate that cGAS inhibition or STING inhibition prevents Cannabidiol-mediated augmentation of IFN ^2 / 3 gene expression, and therefore cGAS-STING pathway signaling is needed for Cannabidiol to increase INF ^2 / 3 gene expression. Figure 20A shows that infection of cells with lentivirus significantly increases the proportion of cells undergoing late-stage apoptosis (i.e. the proportion of cells that are undergoing nuclear fragmentation due to apoptosis), compared to a population of cells that has not been infected with lentivirus. In the wells infected with lentivirus, treatment with 1 µM CBD increases the proportion of cells undergoing late apoptosis by ~50% over wells infected with lentivirus but treated only with vehicle. Treatment of uninfected cells with 1 µM CBD did not increase apoptosis, demonstrating that 1 µM CBD does not increase late-stage apoptosis when lentivirus is not present. Figure 20B shows that adding RU-521 (0.8 µM) to lentivirus-infected HEK293 cells significantly reduced the proportion of cells undergoing late-apoptosis. In cells treated with 1 µM CBD, adding RU-521 also significantly reduced the proportion of cells undergoing late-apoptosis. This demonstrates that cGAS signaling is necessary for CBD to increase late-apoptosis. Figure 20C shows that Adding H-151 (1 µM) to lentivirus-infected HEK293 cells significantly reduced the proportion of cells undergoing late-apoptosis. In cells treated with 1 µM CBD, adding H-151 also significantly reduced the proportion of cells undergoing late-apoptosis. This demonstrates that STING signaling is necessary for CBD to increase late-apoptosis. Figure 21A shows a representative image of HEK293 cells treated only with vehicle controls (0.1% ethanol and 0.1% DMSO) prior to infection with lentivirus. Figure 21B shows a representative image of HEK293 cells treated with 1 µM CBD and 0.1% DMSO prior to infection with lentivirus. Figure 21C shows a representative image of HEK293 cells treated with 0.1% ethanol and 0.8 µM RU-521 prior to infection with lentivirus. Figure 21D shows a representative image of HEK293 cells treated with 0.1% ethanol and 1 µM H-151 prior to infection with lentivirus. Figure 21E shows a representative image of HEK293 cells treated with 1 µM CBD and 0.8 µM RU-521 prior to infection with lentivirus. Figure 21F shows a representative image of HEK293 cells treated with 1 µM CBD and 1 µM H-151 prior to infection with lentivirus. Figure 22A shows that Cannabidiol reduces the proportion of cells that are infected by lentivirus by over half, and this is prevented by the cGAS inhibitor RU-521. Figure 22B shows that Cannabidiol reduces the proportion of cells that are infected by lentivirus by over half, and this is prevented by the STING inhibitor H-151. Figures 23A and 23B show that in lentivirus-infected cells, treatment with 1 µM CBD did not significantly reduce the number of cells after 24 hours. Therefore, the protection that CBD offered against the infection of cells by lentivirus was not dependent on cell death or cell loss. Figure 23A shows that treatment of cells with RU-521 did not significantly affect the number of cells. Thus, the reversal of the protective effects of CBD by RU-521 was not fully dependent on cell death or cell loss. Figure 23B shows that treatment with H-151 caused a small but significant reduction in the number of cells compared to cells untreated with any drug (i.e. either CBD or H-151), or compared to cells treated with CBD alone, but this effect could not fully explain the reversal of the protective effects of CBD by H-151. Figures 24A and 24B show gene expression of INF ^ in HEK293 cells infected with adenovirus, and treated with or without 1 ^M CBD, and with or without the cGAS inhibitor RU-521 (0.8 ^M), or with and without the STING inhibitor H-151 (1 ^M). Figures 24C and 24D shows gene expression of INFγ in HEK293 cells infected with adenovirus, and treated with or without 1 µM CBD, and with or without the cGAS inhibitor RU-521 (0.8 µM), or with and without the STING inhibitor H-151 (1 µM). Figures 24E and 24F show gene expression of INFµ2 / 3 in HEK293 cells infected with adenovirus, and treated with or without 1 µM CBD, and with or without the cGAS inhibitor RU-521 (0.8 µM), or with and without the STING inhibitor H-151 (1 µM).

[0003] Detailed description of the invention Definitions Relative GFP positive cell number (% of total visible cells)” show the number of virus-infected (i.e. GFP-positive) cells divided by the total number of cells and then expressed as a percent, and thus show the proportion of cells that were infected. Number of cells imaged per visual field is the mean number of cells imaged per visual field and indicate that reduction in the total number of infected cells due to effect of CBD as reflected from the “Relative GFP positive cell number” is not due to a reduction in the total number of cells. Roles of Interferons and Interferon-stimulated gene (ISG) products at resisting and controlling pathogens has been reported. The present invention evaluates role of Cannabinoid such as Cannabidiol in the prevention and treatment of interferon-responsive conditions. The interferon responsive conditions also include in addition to treatment or prevention or priming against infectious diseases, treatment for one or more cancers and for autoimmune diseases. Such multiple treatments are possible for an agent like Cannabinoid particularly Cannabidiol which has shown upregulation of all interferons and their downstream effectors. Recently the inventors of the present invention found that pharmaceutical compositions comprising therapeutically effective amount of a one or more Cannabinoids can be employed in an animal including a human or a patient (who can be animal or human) for i) treating Covid-19 infectious disease. ii) producing an enhancement / augmentation of innate immunity; iii) preventing or reducing mutation of Sars-Cov-2 virus; iv) preventing or better preparing for Covid-19 infectious disease in those who are about to get infected. due to effects of Cannabinoids including at least one of the following, i) infected cells undergo apoptosis early after infection; ii) induction of interferon transcription; iii) induction of interferon-induced antiviral effectors. More particularly, one or more Cannabinoids substantially increased gene expression levels of at least one of the 2′-5′-oligoadenylate synthetase 1, 2 and 3 (OAS1, OAS2 and OAS3) in host cells treated with the Cannabinoid and infected with a viral protein of Sars-Cov-2. This effect was more surprising because when inventors treated the host cells with the viral proteins of Sars-Cov-2 virus, no significant reduction in their numbers or no significant response of these cells to the viral proteins such as enhancement / augmentation of innate immunity was noted. This corroborates with the observation of Kulka et al that not all virus infection can cause synthesis of 2-5A and activation of RNase L during virus infection. This may be true with other pathogens as well. If host cell is not able to produce innate immune defense on its own or if the interferons induced or their downstream effectors are not produced in sufficient amount to eliminate pathogen, such cells succumb to the infection. Also, there is likelihood of production of variants due to mutation and / or recombination events which may be more virulent or more transmissible or both. Even vaccines may be less effective for such variants. It has been surprisingly noted that the host cells expressing viral proteins of Sars- Cov-2 virus and treated with certain concentration of various Cannabinoids exhibit one or more of i) apoptosis early after infection ii) induction of interferon transcription and iii) induction of interferon-induced antiviral effectors. Apoptosis early after infection causes apoptosis of infected cells early and eliminates those cells while healthy cells are not affected. This helps in early elimination of infected cells to prevent further spread of infection. It also helps in averting mutations of the viruses. More particularly, OAS family enzymes are produced as downstream effectors of interferons. These Cannabinoid compositions and effects produced are provided in PCT International Application PCT / IN2021 / 050325 filed on March 30, 2021, and PCT International Application PCT / IN2021 / 050699 filed on July 19, 2021 and an unpublished PCT International Application PCT / IN2023 / 050327 filed on April 03, 2023. More particularly, following lines from PCT International Application PCT / IN2023 / 050327 are provided below: Dose of Cannabinoids, particularly Cannabidiol is crucial since it is observed that it has concentration dependent effects and it is desired that the compositions are produced in multiple strengths to address the treatment of various levels of pathologies. A suitable dose of 0.1 mg / kg of body weight to 4000 mg / kg of body weight. The suitable dose can also be 0.1 to 1000 mg / kg of body weight or 0.1 to 500 mg / kg of body weight. The preferred dose can be 0.1 to 100 mg / kg of body weight or from 0.1 to 20 mg / kg of body weight. The invention provides pharmaceutical compositions comprising therapeutically effective amount of Cannabidiol for use in treating an infection in a host / patient wherein said Cannabidiol or composition thereof produces an enhancement / augmentation of innate immunity of the host / patient against said infection. Said action occurs after activation of at least one of the following pathways, i) cGAS-STING pathway; ii) 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway; iii) Both cGAS-STING pathway and 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway; The enhancement / augmentation of innate immunity of the host / patient is due to one or more of the following: a) augmenting induction of interferons; b) augmenting induction of interferon stimulated factors or genes; c) by causing apoptosis of virus infected cells. The invention also provides a method of treating an infection in a host / patient comprising administering a pharmaceutical composition comprising therapeutically effective amount of Cannabidiol as described above. The pharmaceutical compositions and methods of administering such compositions are also found useful in preventing an infection in a host / patient or for use in priming / preparing a host / patient for infection. The infection in a host / patient is caused by one or more of virus, bacteria, fungi, protozoa, parasite. Amongst the viruses, the infection can be due to one or more of the following, i) single stranded RNA viruses; ii) double stranded RNA viruses; iii) double stranded DNA viruses; iv) single stranded DNA viruses; v) DNA viruses replicated through RNA through an RNA intermediate by a reverse transcriptase. More particularly, inventors establish key role of Cannabidiol in augmenting innate immunity in infections that can be caused by Adenovirus and Lentivirus. This finding led the inventors to propose that more viruses are likely to be eliminated due to enhancement of immunity by administering one or more Cannabinoids and include i) single stranded RNA viruses including a) +RNA viruses of family Bromo, Nido, Picorna, Calici, Tombus, Alpha, Flavi and Retro; and b) -RNA viruses of family Orthomyxo, Bunya, Arena of segment type and Paramyxo, Rhabdo of non-segment type; ii) double stranded RNA viruses of family Reo, Cysto, Bima; iii) double stranded DNA viruses belonging to realms Duplodnaviria and Varidnaviria,; and iv) single stranded DNA viruses belonging to realm Monodnaviria. v) DNA viruses replicated through RNA through an RNA intermediate by a reverse transcriptase belonging to the realm Riboviria. Other pathogens which are likely to be affected by the enhanced immune response due to administration of one or more Cannabinoids include bacteria, parasites such as protozoa, fungi, mycobacteria, etc. Thus, more pathogens including bacteria and other microorganisms such as protozoa, subcellular parasites, and fungi, can be eliminated, or infections / diseases caused by them can be treated or averted or animals who are likely to get infected with these pathogens can be better prepared or mutations of pathogens can be averted by employing compositions of one or more Cannabinoids. This is more particularly where cellular defense against pathogens is mediated through interferons and their downstream effectors. Thus, the inventors had proposed and demonstrated that the pathogens and parasites in elimination of which interferons and their downstream effectors play a key role can be eliminated by administration of one or more Cannabinoids. Also, Cannabinoids cause upregulation of several interferons and / or their downstream effectors and cause apoptosis early after infection. This can be of immense importance in treatment, prevention, priming (preparing for attack) against various pathogens. The host cells are better able to prepare for infection including increase in the infectious dose. Administration of Cannabinoids in suitable form including pharmaceutical compositions containing therapeutically effective dose will also help in treatment of Long-Term Infections and persistent / latent infections. Another application where one or more Cannabinoids can be employed include multiple infections. For example, Harris JR et al reports a high prevalence of cryptococcal infection among HIV-infected patients hospitalized with pneumonia in Thailand (Harris JR et al, 2012). In such cases Pharmaceutical compositions of Cannabinoids may be employed. As established, Cannabinoids and particularly Cannabidiol is found to cause induction of several interferons such as IFNα, IFNβ, IFNγ, IFN ^1, and IFN ^2-3 and interferon-stimulated genes such as IFIT, Mx1, OAS1, OAS2, OAS3, OASL, they are ideal agents as a first line and immediate treatment because they can build up a good immune response quite quickly for the patients. This can avoid spread of infection, both within the host and among the host population, mutation to generate more virulent and more transmissible variants and those variants which can make the vaccines ineffective or less effective. Subsequently and if needed more specific treatment for specific pathogen can be provided. Further Cannabinoids can be useful as a starting treatment for Tuberculosis, malaria, dengue etc. which can cause several side effects such as rashes, lack of feeling or tingling in the hands or feet, changes in the eyesight, hair loss, dizziness, headache, sleep disturbances (insomnia and vivid dreams) and psychiatric reactions (anxiety, depression, panic attacks and hallucinations) where Cannabinoids can reduce the duration of treatment or dose or both. Another area where pharmaceutical compositions of Cannabidiol can be employed include combination with vaccines or any other preventive therapy or immunity boosters. The said compositions can reduce the frequency of administration of vaccines or any other preventive therapy or can eliminate the preventive therapy altogether. One of the major advantages of using Cannabinoids against pathogens is early response induced due to building up of an early immunity and a bigger response compared to a normal cellular defense. Early response such as apoptosis early after infection and a bigger response such as generation of interferons or interferon- stimulating genes at multiple times the baseline level is particularly advantageous in providing a stronger defense. Present work is focussed on checking enhancement of host cell immunity by production of interferons and their down-stream effectors by the host cells against pathogen with a nucleic acid genome including RNA or DNA-based viruses, bacteria, parasites, fungi, mycobacteria, etc. after treatment of host cells with one or more Cannabinoids. Of particular interest is evaluation of role of Cannabidiol and other Cannabinoids in producing various desired effects including treating infected host cells, preventing host cells from getting infected, priming of host cells (preparing host cells for attack of pathogen). More particularly, the present work focusses on prevention and treatment of interferon-responsive conditions by one or more Cannabinoids, particularly Cannabidiol. The interferon responsive conditions also include in addition to treatment or prevention or priming against infectious diseases, treatment for one or more cancers and for autoimmune diseases. Such multiple treatments are possible for an agent like Cannabinoid particularly Cannabidiol which has shown upregulation of all interferons and their downstream effectors. Inventors of the present invention had worked on methods to produce OAS family enzymes in levels beyond constitutive levels in infected cells. Thus, of particular interest are 2′-5′-oligoadenylate synthetase (OAS) family of cytosolic dsRNA sensors which restrict replication of multiple viruses. It has been surprisingly noted by the present inventors that Cannabinoids assist host cells in interferon induction and induction of their downstream effectors including 2′-5′-oligoadenylate synthetase (OAS) family of enzymes and thus building innate immunity when viral particles / viral proteins are introduced in the host cells which are treated with one or more Cannabinoids. The inventors state that compositions containing one or more Cannabinoids can be employed for various desired effects including treatment, prevention, priming (preparing for virus attack) against various viruses as provided above. As the effects of Cannabinoids in Sars-Cov-2 virus, which is an RNA virus are established, to establish effects of Cannabinoids in host cells in putting up defense against other viruses, the inventors of the present invention selected a DNA virus an Adenovirus. HEK293 (human embryonic kidney) cells were chosen for infecting with Adenovirus. The virus was made by combining the p-AdEasy-1 virus vector with an empty pShuttle-IRES-hrGFP2 vector, which creates a recombined adenovirus that expresses green fluorescent protein (GFP) under control of the IRES (internal ribosome entry site) promoter. HEK293 cells make and shed infectious virions when infected with this strain of Adenovirus. An experiment was carried out. HEK-293 cells are first treated with Cannabidiol and then infected with adenovirus. Cells that became infected, and started making virally-encoded proteins, glowed green. Cells that didn’t become infected, or that suppressed the intracellular actions of the virus including viral gene and protein expression, or that underwent apoptosis before expressing the green fluorescent protein encoded by the viral genome, did not glow. The detailed process is as follows. HEK-293 cells were seeded in a 24-well plate at a density of 0.1 x 106cells / well in a volume of 2 ml of media. Three separate passages of cells were tested (n=3 biological replicates). One hour later, cells were treated with 0.5, 1, 1.5, 2, 2.5, 3 µM CBD, or vehicle alone (0 µM CBD). Two hours later, cells were infected by adding 0.1 x 106infectious virus particles per well. This would give a multiplicity of infection (MOI) of 1, or 1 infectious unit per cell. Cells were observed at 12, 24, and 48 hours for green glowing cells. At 12 h, cells did not glow. At 24 h, there was only a small amount of glowing. At 48 h, glowing cells were seen clearly. Figures 1A to 1G provide images of glowing HEK-293 cells treated with various concentrations of Cannabidiol such as 0, 0.5, 1, 1.5, 2, 2.5,3 µM and infected with adenovirus. It is clearly seen from these figures (under 4x magnification) that at 48 hrs., infected cells at 0 µM of Cannabidiol were glowing and infected cells that were glowing reduce in number at different concentrations of Cannabidiol wherein the effect is conspicuous already at 0.5 µM concentration of Cannabidiol. The number of glowing cells per field of view at 4x magnification at different concentrations of Cannabidiol are counted and a plot is made as shown in figure 2. Figure 2 shows that the number of glowing cells per field is significantly less when cells are treated with 0.5 µM Cannabidiol, and this effect is even greater when cells are treated with 1 µM Cannabidiol or higher concentrations of Cannabidiol. It is not known from Figure 2 whether there are fewer glowing cells because the cell number has been reduced, for example, by more cells undergoing apoptosis after viral infection, or whether the same number of cells are present, but not infected. Thus, the inventors used automated hemocytometer-based live cell counting employing a Cytation™ 5 Cell Imaging Reader along with Gen5™ Data Analysis Software to enable Live Cell Counting using Phase Contrast and Color Brightfield Imaging, and to enable green fluorescent protein detection at 395 nm / 509 nm (excitation / emission spectra). This apparatus will count adherent cells, including cells that are undergoing early or late-stage apoptosis, but have not yet detached from the plate. Figure 3A provides a plot of the total number of live cells (counted using the Cytation 5 in brightfield mode) following infection at various concentrations of Cannabidiol viz.0.5, 1.0, 1.5, 2.0, 2.5, 3.0 µM CBD, or vehicle alone (0 µM CBD). Figure 3B provides a plot of the percentage of GFP-positive (or infected) cells at various concentrations of Cannabidiol viz.0.5, 1.0, 1.5, 2.0, 2.5, 3.0 µM CBD, or vehicle alone (0 µM CBD). The percentage of GFP-positive (or infected) cells are calculated by dividing the total number of green-glowing cells by the total number of live, visible cells in that field and multiplying by 100. As provided in Figure 3B, the percent of infected cells is significantly reduced at 0.5 µM CBD, and substantially reduce in percent even more at a concentration of 1 µM Cannabidiol or higher. Since the number of cells at 0.5 µM CBD treatment is not reduced, this indicates that the reduced infection at this level is not due to increased apoptosis or cell death but must involve other factors. At 1 µM CBD, the reduction in cell number is only just above 10%, while the reduction in the number of infected cells is much larger, at about two thirds. Thus, the percentage of cells per microscope field that are glowing green due to infection is reduced about one- third when cells are treated with 0.5 µM Cannabidiol and two-thirds when cells are treated with 1 µM Cannabidiol, or higher. Since there is a decrease in the number of cells when infected cultures are treated with 1 µM Cannabidiol, this suggests that apoptosis has increased. However, since the reduction in the number of infected cells is greater than the reduction in the total number of live cells, this indicates that factors other than apoptosis or cell death must also be involved in decreasing the level of infection. To test this, early and late apoptosis indexes were measured (Figures 4A and 4B). The detailed process is as follows. HEK-293 cells were seeded at 10,000 cells / well in a 96-well plate, using 3 different passages of cells (therefore n=3 biological replicates). One hour later, cells were treated with CBD or vehicle control (final concentration, 0.1% ethanol). Two hours later, cells were infected by the addition of GFP-expressing adenovirus at a multiplicity of infection (MOI) = 1. Twenty- four hours later, PI and pSIVA were added to wells, and cells were imaged using a Bio-Tek® Cytation5™ automated cell imager / cell counter. PI was imaged using absorbance / emission spectra of 531 / 647 nm. pSIVA was imaged using absorbance / emission spectra of 469 / 525 nm. Wells were then imaged under brightfield, and total visible cells were counted using the Cytation5 automated cell counting feature. Early and late apoptosis indexes were calculated by dividing the pSIVA or PI measuresments, respectively, by the total number of cells in the same field. Data are analyzed by 1-way ANOVA. Treatment of cells with 1 µM Cannabidiol alone did not increase early or late apoptosis index measures relative to untreated cells, and infection of cells with adenovirus also did not increase early or late apoptosis measures when 0 µM Cannabidiol was treated. This indicates that Cannabidiol at 1 µM does not cause apoptosis in cells, and that without Cannabidiol, cells did not respond properly to Adenovirus infection which should be counteracted by the activation of innate immune responses in cells, including increasing apoptosis. When cells infected with Adenovirus were treated with 0.5 µM Cannabidiol apoptosis index measures did not increase, but when cells infected with Adenovirus were treated with 1 µM Cannabidiol or 2 µM Cannabidiol, early and late apoptosis index measures more than doubled compared to levels seen in control cells that were uninfected and not treated with Cannabidiol. This increased apoptosis will reduce the spread of infection, by removing cells that have become infected so that they cannot generate new infectious virus particles. This will also reduce mutation of virus as the virus is unable to use host machinery to replicate when apoptosis is happening. Potential of such treatment will be immense as infected host cells can selectively undergo apoptosis leaving behind healthy cells. Thus, host machinery of infected cells are destroyed or fragmented and the virus has no place for replication or mutation, suppressing the creation of new variants that can be more infectious or resistant to treatment. As seen earlier in the case of Sars-Cov-2 proteins, Cannabinoids including Cannabidiol cause apoptosis early after infection. Apoptosis early after infection indicates timepoint when the cells undergo apoptosis after infection. This covers both early-stage and late-stage apoptosis as long as they happen early after infection. In the present invention it is noted that cells undergo apoptosis at 24 hrs which indicates that Cannabidiol causes Apoptosis early after infection wherein some cells may be in early apoptosis and some cells may be in late stage of apoptosis. The finding that the decrease in the number of cells infected is greater than the decrease in the total number of cells, means that apoptosis cannot fully explain the protective effects of Cannabidiol in reducing viral infection. There can be more reasons than apoptosis for substantial reduction in % of infected cells. As in Sars-Cov-2 virus proteins, inventors found that there was ii) induction of interferon transcription in the host cell; and iii) induction of interferon-induced antiviral effectors in the host cell. Of particular interest are the interferons. Interferons can have anti-viral effects by inducing hundreds of genes that act to limit viral transcription and replication. Interferons can also be secreted by cells and can act to protect neighboring cells from infection by mechanisms such as stimulating them to make protein kinase R that activates neighbouring cells to reduce protein synthesis. Interferons also increase the recruitment of the adaptive immune system by increasing the expression of major histocompatibility complex I, which increases the recruitment and killing of infected or malignant cells, and major histocompatibility complex II, which presents viral antigens to the adaptive, or acquired immune system cells. Interferons are part of the innate immune system and can also act directly within the cells that synthesize them to induce many interferon-stimulated genes (ISGs) that are anti-viral and can also protect against fungal infections, bacterial infections, malignant cells, parasitic infections and in some cases autoimmunity. The detailed process is as follows. Cells were seeded in a 12-well plate in 2 ml of media at a density of 0.1 x 106cells / well, and 3 biological replicates were tested (three different passages of HEK293 cells were used). One hour after cells were seeded, they were treated with either 1 µM CBD or vehicle. Two hours later, cells were infected with adenovirus that expresses a green fluorescent protein (to allow for visual monitoring of infection), at a multiplicity of infection (MOI) of 1 (i.e.1 infectious unit (IFU) per cell). Forty-eight hours later, mRNA was extracted using the Trizol method, and cDNA was synthesized from RNA. The expression of interferons (IFN) and interferon-stimulated genes (ISGs) was analyzed by qPCR. Expression of IFNs alpha, beta, gamma, lambda 1, and lambda 2-3, and the ISGs Ifit, Mx1, and the OAS family of genes, including OAS1, 2, 3 and L, were analyzed. Data were normalized to GAPDH as a housekeeping gene. The inventors have found that cells infected with adenovirus but not treated with Cannabidiol do not significantly induce IFN ^, IFN ^1, or IFN ^2-3, indicating a poor interferon response to Adenovirus infection without Cannabidiol (Figure 5A, 5D, 5E). However, when cells were treated with 1 µM Cannabidiol, gene expression of IFN ^, IFN ^, IFN ^, IFN ^1, and IFN ^2-3 (Figures 5A-E) all significantly increased in uninfected cells, indicating that 1 µM Cannabidiol can prime cells to be better ready to respond to viral infection. When cells are infected with adenovirus and also treated with 1 µM Cannabidiol, the gene expression of IFN ^, IFN ^, IFN ^, IFN ^1, and IFN ^2-3 (Figures 5A-E) is augmented compared to expression of these genes in cells that are infected but are not treated with 1 µM Cannabidiol, indicating a much better response to infection when Cannabidiol is present. Notably, infected cells treated with 1 µM Cannabidiol have significantly higher expression of IFN ^, IFN ^, IFN ^, IFN ^1, and IFN ^2-3 than uninfected cells either treated with or without 1 µM Cannabidiol, indicating that Cannabidiol augments the response to infection. There are many ISGs that regulate anti-viral processes. Mx1 is an ISG that has antiviral properties. Mx1 expression was significantly higher in uninfected cells treated with 1 µM Cannabidiol than in uninfected cells not treated with Cannabidiol (i.e.0 µM). Mx 1 expression was also significantly higher in infected cells treated with 1 µM Cannabidiol than in uninfected cells not treated with Cannabidiol (Figure 5F). Ifit1 is another ISG with anti-viral effects. Cells infected with Adenovirus did not have higher levels of Ifit1 compared to uninfected cells, indicating a poor interferon-stimulated gene response by these cells to Adenovirus infection. Treatment of uninfected cells with 1 µM Cannabidiol significantly increased the expression of Ifit1, priming cells to be better ready to respond to infection. Treatment of infected cells with 1 µM Cannabidiol caused the greatest increase in Ifit1 gene expression relative to either uninfected cells (treated or untreated with 1 µM Cannabidiol) or Adenovirus-infected cells untreated with Cannabidiol (0 µM). Of particular interest was 2′-5′-oligoadenylate synthetase (OAS) family of cytosolic dsRNA sensors which has been known to restrict replication of multiple viruses. It has been noted that when host cells are infected with viral proteins of Sars-Cov- 2 and treated with one or more Cannabinoids, production of OAS family by host cells including OAS1, OAS2, OAS3, and OASL (which are interferon-induced antiviral effectors) is substantially enhanced. These downstream effectors cause activation of RNase L which causes degradation of Viral RNA and puts up antiviral defense. Since in the present research host cells treated with Cannabidiol and infected with Adenovirus undergo apoptosis, inventors propose additional mechanism of increased production of OAS family by host cells including production of OAS1, OAS2, OAS3, OASL. If host is treated with Cannabidiol before or at the time of infection, adenovirus infected cells can undergo apoptosis due to enhanced production of OAS family proteins by host cells including production of OAS1, OAS2, OAS3, and RNase L activation which leads to degradation of viral RNA transcripts and other cellular RNAs. The apoptosis action is very prompt and happens already by 24 hrs after treatment with Cannabidiol. It has been reported (Hui Meng et al. 2012) that adenovirus synthesizes a highly structured RNA (VAI) to circumvent first immune response. This RNA activates OAS1. However, cellular processing of this RNA results in cleavage of the terminal portion of highly structured RNA (VAI) to change it into VAIΔTS, which then serves as a poor activator of OAS1, essentially lowering OAS1 activity to baseline levels. As a result, this VAIΔTS can down-regulate activation of the OAS / RNAse L system to help the virus evade detection. If Cannabidiol is administered early enough, due to its prompt apoptotic action which is observed in 24 hrs, it reduces viral genome replication, and makes it unlikely that virus changes RNA to escape immune response. It has been interestingly noted that various organisms when infecting host cells cause an innate immune response that triggers production of OAS family by host cells including production of OAS1, OAS2, OAS3. Thereafter RNase L activation is triggered causing degradation of viral RNA and other cellular RNAs that can lead to apoptosis. The inventors of the present invention proposes that the mechanism observed in RNA virus (Sars-Cov-2) and DNA virus (Adenovirus) is also applicable against all infectious organisms which when infecting host cells can have that infection countered by the innate immune response involving production of OAS1, OAS2, OAS3 or OASL. Therefore, Cannabinoids particularly Cannabidiol which may enhance production of OAS1, OAS2, OAS3 is likely to inhibit substantially the survival and replication of M. tuberculosis. The inventors show that 1 µM Cannabidiol significantly upregulates OAS1, OAS2, OAS3, and OASL gene expression levels in cells that are not infected, or in cells that are infected with adenovirus (Figure 5H, 5I, 5J, 5K). When adenovirus is present, 1 µM Cannabidiol further upregulates expression of OAS1, OAS2 and OASL compared to when adenovirus is not present. Adenovirus infection of cells without 1 µM Cannabidiol treatment does not significantly increase gene expression of OAS1, OAS2, OAS3, or OASL compared to levels of gene expression in uninfected cells, indicating that cells have a poor ability to sense adenovirus and respond by activation of innate immunity, but that 1 µM Cannabidiol significantly improves this. Summary of figures Figure 1A-G Figure 1A-G shows images of HEK293 cells infected with adenovirus and treated with CBD, showing (visibly) that fewer cells become infected with adenovirus when CBD is present, and there is a dose-dependent effect. Figures 2, 3A and 3B Figures 2, 3A and 3B show graphs that quantify this effect, in two ways. Figure 2 shows that the total number of visibly infected cells decreases with CBD treatment, with a maximal significant effect (or a plateau in effect) at around 1 uM. Figure 3A shows that CBD decreases the number of cells in plates infected with adenovirus and treated with CBD. At least 1 uM CBD is needed to see a significant decrease in cell number, since 0.5 uM CBD did not decrease cell number. The number of cells present in wells infected with adenovirus decreased more and more with each increase in CBD that occurred up to the maximum level tested, which was 3 ^M. This decrease in cell number that occurs in cells infected with adenovirus and treated with CBD suggests that cells are dying, likely through enhanced apoptosis, which is a defense mechanism employed by infected cells. Figure 3B takes into account the values in Figure 2 and Figure 3A, by dividing the number of glowing (infected) cells at each treatment level in Figure 2 by the number of cells present in that same well (quantified in Figure 3A), and then expressing this as a percentage. This second way of expressing the data also demonstrates that treating adenovirus-infected cells with CBD just prior to infection causes a decrease in the percentage of cells present that were infected, with a maximal effect occurring around 1 ^M. This shows that CBD prevents adenovirus infection likely not just by causing apoptosis, but by other means as well. Figures 4A and 4B Increasing gene expression levels in cells that are uninfected would allow them to be prepared for a possible infection, without activating systems that could harm cells. The absence of an increase in apoptosis in uninfected cells shows that this increase is not harmful to healthy cells. In cells that have been infected with adenovirus, but not treated with CBD, levels of IFNalpha, IFN-lambda1, and IFN-lambda2 / 3 are not higher than in cells that are uninfected (although levels of IFN-beta and IFN-gamma are elevated with infection). The absence of a concerted induction of the expression of these interferon genes in adenovirus-infected cells suggests that the virus is employing strategies to ’hide’ from the innate immune response of the cells, which is mediated in part by interferons. When cells are infected with adenovirus and treated with 1 ^M CBD, gene expression levels of IFN-alpha, IFN-beta, IFN-gamma, IFN-lambda1, and INF- lambda2 / 3 are higher than in uninfected cells not treated with CBD, or in uninfected cells treated with 1 ^M CBD, or in infected cells not treated with CBD, showing that CBD amplifies the response of cells to infection. CBD (1 ^M) also allows cells to activate increased expression of IFN-alpha, IFN- lambda1, and IFN-lambda2 / 3 in response to adenovirus infection, whereas cells infected with adenovirus, but not treated with CBD, were unable to activate increased expression of these anti-viral genes. Figures 5A-G Increasing gene expression levels in cells that are uninfected would allow them to be prepared for a possible infection, without activating systems that could harm cells. The absence of an increase in apoptosis in uninfected cells shows that this increase is not harmful to healthy cells. In cells that have been infected with adenovirus, but not treated with CBD, levels of IFNalpha, IFN-lambda1, and IFN-lambda2 / 3 are not higher than in cells that are uninfected (although levels of IFN-beta and IFN-gamma are elevated with infection). The absence of a concerted induction of the expression of these interferon genes in adenovirus-infected cells suggests that the virus is employing strategies to ’hide’ from the innate immune response of the cells, which is mediated in part by interferons. When cells are infected with adenovirus and treated with 1 ^M CBD, gene expression levels of IFN-alpha, IFN-beta, IFN-gamma, IFN-lambda1, and INF- lambda2 / 3 are higher than in uninfected cells not treated with CBD, or in uninfected cells treated with 1 ^M CBD, or in infected cells not treated with CBD, showing that CBD amplifies the response of cells to infection. CBD (1 ^M) also allows cells to activate increased expression of IFN-alpha, IFN- lambda1, and IFN-lambda2 / 3 in response to adenovirus infection, whereas cells infected with adenovirus, but not treated with CBD, were unable to activate increased expression of these anti-viral genes. Figures 5H-K Figures 5H-K show that CBD augments the induction of OAS1, OAS2, OAS3, and OASL gene expression above levels in control cells, either when they are infected with adenovirus, or when they are uninfected. Increasing OAS gene expression levels in cells that are uninfected would allow them to be prepared for a possible infection, without activating systems that could harm cells. The absence of an increase in apoptosis in uninfected cells shows that this increase is not harmful to healthy cells. OAS family proteins activate RNAse L, which cleaves viral transcripts (stopping the virus from making proteins that it needs to assemble new virus, and propagate), and also promotes cell apoptosis by degrading cellular RNAs, to limit a viral infection and its spread. In cells that have been infected with adenovirus, but not treated with CBD, levels of OAS1, OAS2, OAS3, and OASL gene expression are not higher than in cells that are uninfected and untreated with CBD. The absence of induction of the expression of these anti-viral mediators in adenovirus-infected cells suggests that the virus is employing strategies to ’hide’ from the innate immune response of the cells, which is mediated in part by interferons. When cells are infected with adenovirus and treated with 1 ^M CBD, gene expression levels of OAS1, OAS2, and OASL are higher than in uninfected cells not treated with CBD, or in uninfected cells treated with 1 ^M CBD, or in infected cells not treated with CBD, showing that CBD amplifies the response of cells to infection. CBD (1 ^M) allows cells to activate increased expression of OAS1, OAS2, OAS3, and OASL in response to adenovirus infection, whereas cells infected with adenovirus, but not treated with CBD, were unable to activate increased expression of these anti-viral genes relative to uninfected cells. cGAS – system Since Cannabidiol has exhibited substantial reduction in adenovirus infected cells, inventors of the present invention had proposed the mechanism of activation of cGAS in presence of Cannabidiol as a possibility. The same is endorsed by the fact that this action of Cannabidiol is reversed when cGAS inhibitors were employed. Thus, role of Cannabidiol in augmenting innate immunity of host / patient after activation of cGAS-STING pathway is now confirmed. During DNA virus infection such as adenovirus, host cell innate immune response can also be through cGAS. DNA viruses release DNA in the cytoplasm which may activate the enzyme activity of the nucleotide transferase cGAS. The activated cGAS facilitates the synthesis of 2'3'-cGAMP from ATP and GTP, which activates endoplasmic reticulum membrane protein STING that can be activated by subsequently cyclic dinucleotides (CDNs), then STING escorts tank binding kinase 1 (TBK1) to endosomal compartments to associate with and activate IRF3 and IRF7 that resulted in autophagy and type I IFN responses to limit the proliferation and spread of DNA viruses. ((Zevini et al., 2017; Barber, 2014). During experimentation, the inventors found that Adenovirus hides from the cGAS- STING Pathway by downregulating total levels of proteins in this pathway, or their activation by phosphorylation, while treatment with CBD can reverse this. The inventors demonstrated a causal role for regulation of the cGAS-STING pathway by CBD in the prevention of cellular infection by adenovirus, by using inhibitors of the cGAS-STING pathway, which partially but substantially reversed the protective effects of CBD. This substantial reversal by each of the two inhibitors of the cGAS-STING pathway demonstrate that CBD indeed upregulates the cGAS- STING pathway in adenovirus-infected cells to mediate protection against adenovirus pathology. Summary of the pathway DNA is normally found in the nucleus and mitochondria. When DNA gets into the cytoplasm of cells from pathogenic organisms such as adenoviruses or other DNA- type viruses, or retroviruses such as lentivirus (that reverse transcribe their genomic RNA into DNA), or bacteria, or from dead cells nearby, or from leaking nuclear DNA or leaking mitochondrial DNA, it can bind with cGAS (cyclic GMP-AMP synthase), causing it to become activated. Activated cGAS causes GTP and ATP to react, forming cyclic GMP-AMP (cGAMP). Total protein levels of cGAS don’t change when cGAS is activated by binding to cytosolic DNA. Only it’s activity changes. This is most often measured by analyzing its known effects on other proteins. cGAMP binds to Stimulator of Interferon Genes (STING). STING becomes phosphorylated at serine 366, activating it to its canonically active form. Phosphorylated STING translocates from the endoplasmic reticulum to the Golgi, where it binds Tank-Binding Kinase 1 (TBK1). TBK1 becomes activated by trans-autophosphorylation at serine 172. Phosphorylated TBK1 phosphorylates IRF3 at serine 396, which causes it to bind to DNA to induce the transcription of interferons (i.e. to increase the gene expression of interferons), particularly Type 1 IFNs (i.e. IFN-alpha and IFN-beta). Notably, RNA-type viruses activate OAS proteins instead of cGAS, and RNA-type viruses tend not to induce Type 1 IFNs, but rather activate Type II and Type III IFNs. Interferons are proinflammatory cytokines that help to mediate the innate immune response in cells. They also help to recruit circulating immune cells (in the acquired immune system) to the site of infection, to help mediate clearance of the infection, but present work has largely focused on the innate immune response inside cells that are infected with a DNA type virus or retrovirus. The inventors studied following effects of CBD i) cGAS Regulation / Total levels of cGAS proteins; ii) Total STING Regulation / Total levels of STING proteins iii) Phospho-STING Regulation / Total levels of Phospho-STING proteins; iv) Total TBK1 Regulation / Total levels of TBK1 protein; v) P-TBK1 Regulation / Total levels of Phospho-TBK1 protein; vi) Reversal of the effects of CBD with cGAS-STING Pathway inhibitors. cGAS Regulation / Total levels of cGAS proteins Figures 6A-6C As provided in Figures 6A, 6B and 6C, total levels of cGAS protein are not changed by adenoviral infection of HEK293 cells, or by treatment of cells with CBD, or combinations (i.e. adenoviral infection in CBD-treated cells). This was not unexpected, since cGAS is activated by binding to cytosolic DNA (e.g. from a virus such as adenovirus) and so cGAS activity can change significantly without cGAS levels changing. Total STING Regulation / Total levels of STING proteins Figures 7A-7C Figures 7A-7C indicate effects of CBD on Total STING Regulation and indicate that total levels of STING protein are not significantly changed by adenoviral infection of HEK293 cells, or by treatment of cells with CBD, or combinations (i.e. adenoviral infection in CBD treated cells). This was not unexpected, since the activity of this protein is regulated primarily by changes in phosphorylation state (and therefore changes in the activation state of the protein), rather than total protein level. Phospho-STING Regulation / Total levels of Phospho-STING proteins Figures 8A – 8C Figures 8A – 8C indicate effect of CBD on Phospho-STING Regulation and indicate that Levels of phospho-STING protein, detected by an antibody that recognizes P-STING that has been phosphorylated at serine 366, were significantly reduced in cells infected with adenovirus, by over 60% compared to uninfected cells, if CBD was not added. This shows that adenovirus acts in HEK293 cells to try to evade the innate immune response by decreasing the activation of P-STING (which occurs through cGAS activation, and cGAMP production). Further, when cells were treated with 1 ^M CBD, it completely prevented the ability of adenovirus to down-regulate STING phosphorylation at serine 366 (and therefore STING activation). Total TBK1 Regulation / Total levels of TBK1 protein Figures 9A – 9C Figures 9A – 9C - Levels of total TBK1 protein were significantly reduced in cells infected with adenovirus, by over 65% compared to uninfected cells, if CBD was not added. If 1 ^M CBD was added, this detrimental effect of adenovirus, which could limit the innate immune response of an infected cell, was reversed. This shows that adenovirus acts in HEK293 cells to try to evade the innate immune response by decreasing the level of total TBK1, and CBD acts to prevent that effect. This was unexpected, since this pathway is often regulated by changes in post- translational modifications, such as phosphorylation, rather than changes in total levels of pathway proteins. P-TBK1 Regulation / Total levels of Phospho-TBK1 protein Figures 10A – 10C Figures 10A – 10C - Levels of phospho-TBK1 protein (phosphorylated at serine 172) were significantly reduced in cells infected with adenovirus, by over 50% compared to uninfected cells, if CBD was not added. If 1 ^M CBD was added, this detrimental effect of adenovirus was reversed. This shows that adenovirus acts in HEK293 cells to try to evade the innate immune response by decreasing the level of total TBK1, and CBD acts to prevent that effect. • Phospho-TBK1 is the active form of this protein. • It should be noted that since levels of total TBK1 are reduced, the reduction in phosphorylation likely reflects decreased levels of the protein, as well as a decreased activation state. Reversal of the effects of CBD with cGAS-STING Pathway inhibitors Figure 11 Reversal of the effects of CBD with cGAS-STING Pathway inhibitors, showing a causal role for the regulation of these proteins by CBD in the mediation of CBD’s infection prevention effects. RU-521 is a potent cGAS inhibitor that suppresses cGAS-mediated signaling in vitro and in vivo. Adding RU-521 (0.8 ^M) to adenovirus-infected HEK293 cells did not significantly increase the level of infection relative to cells that did not have RU-521 added. Interestingly, this shows that in cells not treated with CBD, cGAS- mediated signaling wasn’t providing much (or any) protective effect against adenovirus. However, in cells treated with 1 ^M CBD, adding RU-521 roughly doubled the relative level of cells that were infected with adenovirus, showing that inhibition of cGAS activity can partially reverse the protective effect of CBD against adenovirus infection. A non-specific effect of RU-521 was not seen in the absence of CBD (i.e. in cells infected with adenovirus but not treated with CBD, RU-521 did not raise infection levels). Since a non-specific effect was not seen, this work shows that CBD prevents infection, in part, through modulation of cGAS- mediated signaling. Put another way, the protective effect of CBD against adenovirus infection was dependent, at least in part, on cGAS-mediated signaling in this experiment. Figure 12 Reversal of the effects of CBD with cGAS-STING Pathway inhibitors, showing a causal role for the regulation of these proteins by CBD in the mediation of CBD’s infection prevention effects. H-151 is a potent STING inhibitor when used in cells and mice. It has previously been shown to reduce TBK1 activation by STING. H-151 covalently binds to STING at a cysteine residue (Cys91) which prevents STING from being palmitoylated. Palmitoylation is needed for STING to act as a signaling hub, recruiting TBK1 and causing the induction of interferons and other proinflammatory genes. As a result, H-151 prevents TBK1 activation and the induction of interferons. Adding H-151 (1 uM) to adenovirus-infected HEK293 cells did not significantly increase the level of infection relative to cells that did not have H-151 added. Interestingly, this shows that in cells not treated with CBD, STING-mediated signaling wasn’t providing much (or any) protective effect against adenovirus. However, in cells treated with 1 uM CBD, adding H-151 more than doubled the relative level of cells that were infected with adenovirus, showing that inhibition of STING activity can partially and significantly reverse the protective effect of CBD against adenovirus infection. A non-specific effect of H-151 was not seen in the absence of CBD (i.e. in cells infected with adenovirus but not treated with CBD, H-151 did not raise infection levels). Again, this highlights that adenovirus is likely ‘hiding’ from the cGAS- STING activity of the innate immune system, which should be activated by infection (but is not in these studies). Since a non-specific effect was not seen, this work shows that CBD prevents infection, in part, through modulation of STING-mediated signaling. Put another way, the protective effect of CBD against adenovirus infection was dependent, at least in part, on STING signaling in these experiments. Animal studies and results Final experiments are conducted on mice to find out whether CBD inhibits infection of mice by Adenovirus. The purpose of this experiment was to test whether treatment of mice with CBD can protect against infection with adenovirus. Animals (male mice) are selected and treatments are given as described under examples. One group received only vehicle (sesame oil, 1 ml / kg / day, by oral gavage) for 3 days. Another group received CBD (80 mg / kg / day, by oral gavage, dissolved in sesame oil carrier) for 3 days. On the third day, all mice were injected with 2 x 108infectious units of adenovirus. Mice continued to receive daily doses of CBD or vehicle oil by oral gavage until the end of the study. Mice from the vehicle and CBD groups were euthanized 2-, 4-, and 6-days post- injection. Brain, heart, lungs, liver, kidneys, gonadal fat and serum were harvested and flash frozen for later analysis (n=3). Genomic DNA extraction and qPCR Genomic DNA was extracted from the liver as described under examples. Further, Genomic DNA was quantified by Nanodrop, and subsequently analyzed by real time PCR (100 ng total DNA). Total levels of the viral hexon gene and mouse Pnpla2 gene (also called Atgl gene) and levels of the 18s gene were analyzed. Real-time PCR was used to measure levels of the relative number of hexon genes in mouse liver tissues. Hexon genes are found in the adenovirus genome, and are not normally found in mouse cells or in the mouse genome. Detection of the number of hexon DNA genes is a marker of how much virus is present in a mouse tissue, or the level of infection in a mouse tissue. Taqman real-time PCR was used to examine the total levels of 18s gene. This analysis is useful for detecting the total amount of mouse chromosomal DNA in a liquid sample. This assay cannot detect adenoviral DNA, since the 18s gene is not present in the adenovirus genome. This measure was used as one of the normalization factors in the analysis. By normalizing detectable hexon gene (DNA) levels to 18s DNA levels, measures taken reflect the amount of virus DNA present relative to mouse DNA, or the amount of virus per mouse cell. The relative number of copies of the Pnpla2 gene in each sample was measured using primers that are specific for the first exon of this gene. This assay cannot detect adenoviral DNA, since the mouse Pnpla2 gene is not present in the adenovirus genome. This measure was used as one of the normalization factors in present analysis. By normalizing detectable hexon gene (DNA) levels to mouse Pnpla2 DNA levels, measures taken by inventors reflect the amount of virus DNA present relative to mouse DNA, or the amount of virus per mouse cell. Figure 13 As shown in Figure 13, there is provided quantification of the relative level of adenovirus hexon DNA detected in mouse liver relative to mouse chromosomal 18s DNA. All levels were computed as fold-difference relative to the average level of hexon DNA / 18s DNA in livers from mice treated with CBD on day 2 of infection, which were set at 1.0 (+ / -0.50). Livers from mice treated only with vehicle had 119.3-fold higher levels of hexon DNA / 18sDNA on day 2, 602.2-fold higher levels on day 4, and 9831.8-fold higher levels on day 6, relative to mice on day 2 treated with CBD. This indicates active replication of the virus when CBD was not given. The relative level of infection in livers of mice treated only with vehicle increased 5-fold from day 2 to day 4, and 82-fold from day 2 to day 6, with an increase of over 16-fold from day 4 to day 6. From day 2 to day 4, the relative level of hexon DNA / 18s DNA detected in livers of mice given CBD increased slightly, by 2.53-fold, although it remained 119-fold to 238-fold lower than levels in control mice given only vehicle at matched timepoints. However, the relative level of detectable virus in livers of mice treated with CBD was not significantly different between day 2 and day 6, and day 4 and day 6, indicating an excellent ability of mice to contain this virus and prevent replication after infection when CBD was given. Average detected 18s gene levels varied by less than 3% between samples, indicating that highly similar amounts of extracted tissue were analyzed, and amount of input material used for analysis is not a source of variation between groups. Figure 14 As shown in Figure 14, there is provided quantification of the relative level of adenovirus hexon DNA detected in mouse liver relative to quantification of a mouse chromosomal gene (exon 1 of Pnpla2). This figure provides another analysis of the hexon data, relative to a different mouse chromosomal gene. It serves to provide an additional analysis validating approach of inventors with 18s. All levels were computed as fold-difference relative to the average level of hexon DNA / Pnpla2 DNA in livers from mice treated with CBD on day 2 of infection, which were set at 1.0 (+ / -0.64). Livers from mice treated only with vehicle had 100.4-fold higher levels of hexon DNA / Pnpla2 DNA on day 2, 517.58-fold higher levels on day 4, and 7620.27-fold higher levels on day 6, relative to mice on day 2 treated with CBD. This indicates active replication of the virus when CBD was not given. The relative level of infection in livers of mice treated only with vehicle increased ~5-fold from day 2 to day 4, and 76-fold from day 2 to day 6, with an increase of almost 15-fold from day 4 to day 6. The relative level of detectable virus in livers of mice treated with CBD (as determined by relative levels of hexon DNA / Pnpla2 DNA was not significantly different between day 2, day4, or day 6, indicating an excellent ability of mice to contain this virus and prevent replication after infection when CBD was given. Average detected Pnpla2 gene levels varied less than 6% between samples, indicating that highly similar amounts of extracted tissue were analyzed, and amount of input material used for analysis is not a source of variation between groups. Action of CBD in retroviral infections Lentiviruses are a class of retroviruses that include human immunodeficiency virus (HIV), simian immunodeficiency virus (SIV), feline immunodeficiency virus (FIV) and equine infectious anemia virus (EIAV). Lentiviruses are a subtype of retrovirus. Lentiviruses are capable of infecting non- dividing and actively dividing cell types. The Lentivirus employed in this study was purchased from Genecopoeia.com, and consisted of purified, pre-made, high-titre lentiviral particles expressing enhanced green fluorescent protein (GFP). Lentiviruses are commonly used in labs to deliver genes to cells, in order to make cell lines that stably integrate the viral genes into their nuclear chromosomes, then copy and transmit these genes to daughter cells when they replicate. Lentiviruses are retroviruses (from the family Retroviridae) that are RNA-type viruses. However, they differ from many types of classical RNA-type viruses, like coronaviruses, in important ways. Upon entry to cells, Lentiviruses will reverse- transcribe their RNA genome to form complementary DNA (cDNA), and then make this cDNA into double-stranded DNA, which they can then insert (using an integrase enzyme) into the nuclear DNA of the host cell. Most experimental lentiviruses used in labs, including this one, are derived from the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS). They can infect cells, but have been engineered for safety to lack the ability to replicate in cells that they infect, or to cause the AIDS disease if humans are exposed. However, they can still insert DNA into any cell that they infect, and thus must be handled as Biosafety Level 2 materials. There is currently no vaccine that protects people against HIV. An estimated 0.7% of adults (age 15-49 years) are living with HIV, globally. It is estimate that 1.5 million new infections occurred in 2021 https: / / www.who.int / data / gho / data / themes / hiv-aids. Thousands of Canadians, and tens of thousands of Americans are infected with HIV annually. Figures 15A – 15C Figures 15A – 15C show gene expression of INF ^ in HEK293 cells infected with lentivirus, and treated with or without 1 ^M CBD, and with or without the cGAS inhibitor RU-521 (0.8 ^M), or with and without the STING inhibitor H-151 (1 ^M). Treatment of infected HEK293 cells with 1 ^M CBD increased the expression of INF ^ by ~4-fold (figure 15A). However, when cells were infected with lentivirus, and treated with RU-521, expression of INF ^ was reduced by 7- to 20-fold (figure 15B). This indicates that RU-521 significantly reduces the activation of INF ^ expression in cells treated with or without 1 ^M CBD, showing that cGAS activation is required for the increased INF ^ expression caused by 1 ^M CBD in infected cells. When cells were infected with lentivirus, and treated with H-151, expression of INF ^was reduced by 13- to 48-fold (figure 15C). This indicates that H-151 significantly reduces the activation of INF ^ expression in cells treated with or without 1 ^M CBD, showing that STING activity is required for the increased INF ^ expression caused by 1 ^M CBD in infected cells. Data are means + / - SEM. N=4 (infected) and N=10 (uninfected). ***P<0.001,****P<0.0001, ns = not significantly different. Figures 16A – 16C Figures 16A- 16C show gene expression of INF ^ in HEK293 cells infected with lentivirus, and treated with or without 1 ^M CBD, and with or without the cGAS inhibitor RU-521 (0.8 ^M), or with and without the STING inhibitor H-151 (1 ^M). Treatment of HEK293 cells with 1 ^M CBD did not significantly increase the expression of interferon (IFN) beta (INF ^) in uninfected cells. Infection of cells with the model retrovirus, lentivirus, caused a small increase in the expression of INF ^ of approximately 6-fold (figure 16A). However, when cells were infected with lentivirus, and treated with 1 ^M CBD, INF ^ gene expression rose by approximately 17-fold (compared to untreated / uninfected cells). The level of INF ^ gene expression in CBD-treated, lentivirus-infected cells, was significantly higher than the level of INF ^ in vehicle- treated, lentivirus-infected cells, indicating that 1 ^M CBD significantly enhances the INF ^ response to lentivirus infection (figure 16A). Treatment of infected HEK293 cells with 1 ^M CBD increased the expression of INF ^ by ~3-fold. However, when cells were infected with lentivirus, and treated with RU-521, expression of INF ^ was reduced by 22- to 90-fold. This indicates that RU-521 significantly reduces the activation of INF ^ expression in cells treated with or without 1 ^M CBD, showing that cGAS activation is required for the increased INF ^ expression caused by 1 ^M CBD in infected cells (figure 16B). When cells were infected with lentivirus, and treated with H-151, expression of INF ^ was reduced by 16- to 88-fold. This indicates that H-151 significantly reduces the activation of INF ^ expression in cells treated with or without 1 ^M CBD, showing that STING activity is required for the increased INF ^ expression caused by 1 ^M CBD in infected cells (figure 16C). Data are means + / - SEM. N=4 (infected) and N=10 (uninfected). ***P<0.001,****P<0.0001, ns = not significantly different. Figures 17A – 17C Figures 17A- 17C show gene expression of INF ^ in HEK293 cells infected with lentivirus, and treated with or without 1 ^M CBD, and with or without the cGAS inhibitor RU-521 (0.8 ^M), or with and without the STING inhibitor H-151 (1 ^M). Treatment of HEK293 cells with 1 ^M CBD did not significantly increase the expression of interferon (IFN) gamma (INF ^) in uninfected cells. Infection of cells with the model retrovirus, lentivirus, caused a small increase in the expression of INF ^ of approximately 6-fold (figure 17A). However, when cells were infected with lentivirus, and treated with 1 ^M CBD, INF ^ gene expression rose by approximately 9-fold (compared to untreated / uninfected cells) (figure 17A). Data are means + / - SEM. N=4 (infected) and N=10 (uninfected). *P<0.05, ***P<0.001 ****P<0.0001. Treatment of infected HEK293 cells with 1 ^M CBD significantly increased the expression of INF ^ by ~2-fold (figure 17B). However, when cells were infected with lentivirus, and treated with RU-521, expression of INF ^ was reduced by 12- 16-fold. This indicates that RU-521 significantly reduces the activation of INF ^ expression in cells treated with or without 1 ^M CBD, showing that cGAS activation is required for the increased INF ^ expression caused by 1 ^M CBD in infected cells (figure 17B). When cells were infected with lentivirus, and treated with H-151, expression of INF ^ was reduced by 16-fold. This indicates that H-151 significantly reduces the activation of INF ^ expression in cells treated with or without 1 ^M CBD, showing that STING activity is required for the increased INF ^ expression caused by 1 ^M CBD in infected cells (figure 17C). Data are means + / - SEM. N=4 (infected) and N=10 (uninfected). *P<0.05, ***P<0.001,****P<0.0001, ns = not significantly different. Figures 18A – 18C Figures 18A- 18C show gene expression of INF ^1 in HEK293 cells infected with lentivirus, and treated with or without 1 ^M CBD, and with or without the cGAS inhibitor RU-521 (0.8 ^M), or with and without the STING inhibitor H-151 (1 ^M). Treatment of HEK293 cells with 1 ^M CBD did not increase the expression of interferon (IFN) lambda λ1 (INF λ1) in uninfected cells. Infection of cells with the model retrovirus, lentivirus, caused a small increase in the expression of INF λ1 of approximately 7-fold (figure 18A). However, when cells were infected with lentivirus, and treated with 1 ^M CBD, INFλ1 gene expression rose by approximately 17-fold (relative to uninfected / untreated cells). The level of INF λ1 gene expression in CBD-treated, lentivirus-infected cells, was significantly higher than the level of INF λ1 in vehicle-treated, lentivirus-infected cells, indicating that 1 ^M CBD significantly enhances the INF λ1 response to lentivirus infection (figure 18A). Treatment of infected HEK293 cells with 1 ^M CBD increased the expression of INFλ1 by ~2.4-fold. However, when cells were infected with lentivirus, and treated with RU-521, expression of INF λ1 was reduced by 18- to 30-fold. This indicates that RU-521 significantly reduces the activation of INF λ1 expression in cells treated with or without 1 ^M CBD, showing that cGAS activation is required for the increased INF λ1 expression caused by 1 ^M CBD in infected cells (figure 18B). When cells were infected with lentivirus, and treated with H-151, expression of INFλ1 was reduced by 9- to 47-fold. This indicates that H-151 significantly reduces the activation of INF λ1 expression in cells treated with or without CBD, showing that STING activity is required for the increased INF λ1 expression caused by 1 ^M CBD in infected cells (figure 18C). Data are means + / - SEM. N=4 (infected) and N=10 (uninfected),****P<0.0001, ns = not significantly different. Figures 19A – 19C Figures 19A- 19C show gene expression of INFλ2 / 3 in HEK293 cells infected with lentivirus, and treated with or without 1 ^M CBD, and with or without the cGAS inhibitor RU-521 (0.8 ^M), or with and without the STING inhibitor H-151 (1 ^M). Treatment of HEK293 cells with 1 ^M CBD did not increase the expression of interferon (IFN) lambda 2 / 3 (INF λ2 / 3) in uninfected cells. Infection of cells with the model retrovirus, lentivirus, caused a small increase in the expression of INFλ2 / 3 of approximately 3-fold (figure 19A). However, when cells were infected with lentivirus, and treated with 1 ^M CBD, INFλ2 / 3 gene expression rose by approximately 9-fold (relative to uninfected and untreated cells). The level of INFλ2 / 3 gene expression in CBD-treated, lentivirus- infected cells, was significantly higher than the level of INFλ2 / 3 in vehicle treated, lentivirus-infected cells, indicating that 1 ^M CBD significantly enhances the INFλ2 / 3 response to lentivirus infection (figure 19A). Treatment of infected HEK293 cells with 1 ^M CBD increased the expression of INFλ2 / 3 by ~3-fold. However, when cells were infected with lentivirus, and treated with RU-521, expression of INFλ2 / 3 was reduced by 8-13-fold. This indicates that RU-521 significantly reduces the activation of INFλ2 / 3 expression in cells treated with or without 1 ^M CBD, showing that cGAS activation is required for the increased INFλ2 / 3 expression caused by 1 ^M CBD in infected cells (figure 19B). When cells were infected with lentivirus, and treated with H-151, expression of INFλ2 / 3 was reduced by 4- to 61-fold. This indicates that H-151 significantly reduces the activation of INFλ2 / 3 expression in cells treated with or without 1 ^M CBD, showing that STING activity is required for the increased INFλ2 / 3 expression caused by 1 ^M CBD in infected cells (figure 19C). . Data are means + / - SEM. N=4 (infected) and N=10 (uninfected), *P<0.05, **P<0.01, ****P<0.0001, ns = not significantly different. Figures 20A - 20C Measurement of late apoptosis Only late-stage apoptosis was measured, since the fluorophore that is typically used to measure early-stage apoptosis has an emission / excitation spectra that overlaps with the green-fluorescent protein in the lentivirus. The experimental details for Measurement of Late Apoptosis are provided under examples. Figure 20A This figure shows that infection of cells with lentivirus significantly increases the proportion of cells undergoing late-stage apoptosis (i.e. the proportion of cells that are undergoing nuclear fragmentation due to apoptosis), compared to a population of cells that has not been infected with lentivirus. This shows that cells have some ability to recognize this lentivirus, activating apoptosis as a protective measure of the cell’s innate anti-viral defense process, to try to prevent the infection from taking hold in the cell, and spreading. When uninfected cells are treated with 1 ^M CBD, there is no significant change in the proportion of cells undergoing late-stage apoptosis, showing that 1 ^M CBD is safe for cells that are not infected with lentivirus. When lentivirus-infected cells are treated with 1 ^M CBD, the proportion undergoing late-stage apoptosis is significantly higher than when lentivirus- infected cells are treated only with the vehicle, indicating that 1 ^M CBD significantly augments the pro-apoptotic action of cells in response to lentivirus infection. This means that cells become better able to respond to lentivirus infection by undergoing apoptosis when treated with 1 ^M CBD. ***P<0.001, ****P<0.0001, ns = not significantly different, (n=5). Figure 20B Cannabidiol increases the proportion of lentivirus-infected cells that are undergoing apoptosis, and this is prevented by the cGAS inhibitor RU-521. RU-521 is a potent cGAS inhibitor that suppresses cGAS-mediated signaling in vitro and in vivo. In the wells infected with lentivirus, treatment with 1 ^M CBD increases the proportion of cells undergoing late apoptosis by ~50%. In response to viral infection, cells can activate apoptosis, leading to late-stage apoptosis and cell death. This process involves fragmentation of the nucleus, and the cell materials, and can help prevent viral replication and viral spread in the body. It is an innate cellular defense mechanism through which individual cells act to limit the exposure of the rest of the body to a virus infection. Adding RU-521 (0.8 ^M) to lentivirus-infected HEK293 cells significantly reduced the proportion of cells undergoing late-apoptosis, demonstrating that cGAS activation is needed for HEK293 cells to undergo apoptosis in response to lentivirus infection. In cells treated with 1 ^M CBD, adding RU-521 reversed the increase in late- apoptosis that was caused by 1 ^M CBD treatment of lentivirus-infected cells, which shows that cGAS activation is needed for 1 ^M CBD to enhance late-stage apoptosis in infected HEK-293 cells. **P<0.01, ****P<0.0001, ns = not significantly different, (n=5). Figure 20C Cannabidiol increases the proportion of lentivirus-infected cells that are undergoing apoptosis, and this is prevented by the STING inhibitor H-151. H-151 is a potent STING inhibitor that suppresses STING-mediated signaling in vitro and in vivo. In the wells infected with lentivirus, treatment with 1 ^M CBD increases the proportion of cells undergoing late-stage apoptosis by ~50%. In response to viral infection, cells can activate apoptosis, leading to late-stage apoptosis and cell death. This process involves fragmentation of the nucleus, and the cell materials, and can help prevent viral replication and viral spread in the body. It is an innate cellular defense mechanism through which individual cells act to limit the exposure of the rest of the body to a virus infection. Adding H-151 (1 ^M) to lentivirus-infected HEK293 cells significantly reduced the proportion of cells undergoing late-apoptosis, demonstrating that STING activation is needed for HEK293 cells to undergo apoptosis in response to lentivirus infection. In cells treated with 1 ^M CBD, adding H-151 also significantly reduced the proportion of cells undergoing late-apoptosis, to levels that were between (but not significantly different from) levels observed in infected cells that were not treated with CBD or H-151, and cells that were not treated with CBD but treated with H- 151. Since H-151 reversed the increase in late-apoptosis that was caused by 1 ^M CBD treatment of lentivirus-infected cells, this shows that STING activation is needed for 1 ^M CBD to enhance late-stage apoptosis in infected HEK-293 cells. **P<0.01, ****P<0.0001, ns = not significantly different, (n=5). Figure 21A shows a representative image of HEK293 cells treated only with vehicle controls (0.1% ethanol and 0.1% DMSO) prior to infection with lentivirus. Figure 21B shows a representative image of HEK293 cells treated with 1 ^M CBD and 0.1% DMSO prior to infection with lentivirus. Figure 21C shows a representative image of HEK293 cells treated with 0.1% ethanol and 0.8 ^M RU-521 prior to infection with lentivirus. Figure 21D shows a representative image of HEK293 cells treated with 0.1% ethanol and 1 ^M H-151 prior to infection with lentivirus. Figure 21E shows a representative image of HEK293 cells treated with 1 ^M CBD and 0.8 ^M RU-521 prior to infection with lentivirus. Figure 21F shows a representative image of HEK293 cells treated with 1 ^M CBD and 1 ^M H-151 prior to infection with lentivirus. Figures 22A and 22B Figure 22A shows that Cannabidiol reduces the proportion of cells that are infected by lentivirus by over half, and this is prevented by the cGAS inhibitor RU-521. In the wells infected with lentivirus, but not treated with CBD, 34.1% of cells glowed green, indicating that cells had become infected with the virus. In the wells infected with lentivirus, and pre-treated with 1 ^M CBD, only 16.0% of cells glowed green. This shows that exposing cells to 1 ^M CBD prior to virus exposure reduced infection with lentivirus by over 50%. RU-521 is a potent cGAS inhibitor that suppresses cGAS-mediated signaling in vitro and in vivo. Adding RU-521 (0.8 ^M) to lentivirus-infected HEK293 cells did not significantly increase the level of infection relative to cells that did not have RU-521 added. This shows that in cells not treated with CBD, cGAS-mediated signaling wasn’t providing much of a protective effect against lentivirus. This may mean that lentivirus was evading detection by cells, which should activate the cGAS-STING system. However, in cells treated with 1 ^M CBD, adding RU-521 caused an ~1.9-fold increased in the relative level of cells that were infected with lentivirus, showing that inhibition of cGAS activity can reverse the protective effect of CBD against lentivirus infection. The level of lentivirus infection in cells treated with 1 ^M CBD plus 0.8 ^M RU- 521 was not significantly different from the level of infection in cells that were not treated with either, showing that RU-521 inhibition of cGAS-mediated signaling reverses the protective effects of CBD, indicating that cGAS-mediated signaling is critical for the protective effects of CBD against lentivirus protection. Figure 22B Cannabidiol reduces the proportion of cells that are infected by lentivirus by over half, and this is prevented by the STING inhibitor H-151. H-151 is a potent and specific STING inhibitor that is used in cells and mice. It has previously been shown to reduce TBK1 activation by STING. H-151 covalently binds to STING at a cysteine residue (Cys91) which prevents STING from being palmitoylated. Palmitoylation is needed for STING to act as a signaling hub, recruiting TBK1 and causing the induction of interferons and other pro- inflammatory genes. As a result, H-151 prevents TBK1 activation and the induction of interferons. Adding H-151 (1 ^M) to adenovirus-infected HEK293 cells increased the level of infection relative to cells that did not have H-151 treatment by ~26%, which shows that activation of STING in HEK293 cells provides some protection against lentivirus infection, and inhibition of that pathway diminishes the ability of cells to prevent lentivirus infection. However, in cells treated with 1 ^M CBD, adding H-151 almost doubled the relative level of cells that were infected with lentivirus (i.e. increased infection by 1.89-fold) , showing that inhibition of STING activity can partially reverse the protective effect of CBD against adenovirus infection. The level of lentivirus infection in cells treated with 1 ^M CBD plus 1 ^M H-151 was not significantly different from the level of infection in cells that were not treated with either, showing that H-151 inhibition of STING-mediated signaling reverses the protective effects of CBD, indicating that STING-mediated signaling is critical for the protective effects of CBD against lentivirus protection. Data are means + / -SEM. ***P<0.001; ****P<0.0001; ns=not significant. (n=5) Figure 23A and 23B In lentivirus-infected cells, treatment with 1 ^M CBD did not significantly reduce the number of cells after 24 hours. Therefore, the protection that CBD offered against the infection of cells by lentivirus was not dependent on cell death or cell loss. Treatment of cells with RU-521 did not significantly affect the number of cells. Thus, the reversal of the protective effects of CBD by RU-521 was not fully dependent on cell death or cell loss. Treatment with H-151 caused a small but significant reduction in the number of cells compared to cells untreated with any drug (i.e. either CBD or H-151), or compared to cells treated with CBD alone. However, there was no significant difference in any other comparisons between cell numbers, indicating that the reversal of protective effects of CBD by H-151 could not be explained by cell death or loss. The data at 24 hours shows that CBD can also protect cells against lentivirus infection through mechanisms that do not require cell death, but that do require cGAS-STING pathway activity. Data are means + / -SEM. *P<0.05; ns=not significant. (n=5). Figures 24A to 24E – Additional Adenovirus experiments Figures 24A and 24B show gene expression of INF ^ in HEK293 cells infected with adenovirus, and treated with or without 1 ^M CBD, and with or without the cGAS inhibitor RU-521 (0.8 ^M), or with and without the STING inhibitor H-151 (1 ^M). Treatment of adenovirus-infected HEK293 cells with 1 ^M CBD increased the expression of INF ^ by ~2.3-fold (figure 24A and 24B). However, treatment of cells with RU-521 or H-151 completely reversed this increase (figure 24A and 24B), indicating that cGAS-STING pathway activity is required for the increased INF ^ expression caused by 1 ^M CBD in adenovirus-infected cells. Data are means + / - SEM. (N=4-10). ***P<0.001,****P<0.0001, ns = not significantly different. Figures 24C and 24D shows gene expression of INFγ in HEK293 cells infected with adenovirus, and treated with or without 1 µM CBD, and with or without the cGAS inhibitor RU-521 (0.8 µM), or with and without the STING inhibitor H-151 (1 µM). Treatment of adenovirus-infected HEK293 cells with 1 ^M CBD increased the expression of INF ^ by ~2.2-fold (figures 24C and 24D). However, treatment of cells with RU-521 or H-151 completely reversed this increase (figures 24C and 24D), indicating that cGAS-STING pathway activity is required for the increased INF ^ expression caused by 1 ^M CBD in adenovirus-infected cells. Data are means + / - SEM. (N=4-10).****P<0.0001, ns = not significantly different. Figures 24E and 24F show gene expression of INFµ2 / 3 in HEK293 cells infected with adenovirus, and treated with or without 1 µM CBD, and with or without the cGAS inhibitor RU-521 (0.8 µM), or with and without the STING inhibitor H-151 (1 µM). Treatment of adenovirus-infected HEK293 cells with 1 ^M CBD increased the expression of INF ^2 / 3 by ~2.1-fold (figures 24E and 24F). However, treatment of cells with RU-521 or H-151 completely reversed this increase (figures 24E and 24F), indicating that cGAS-STING pathway activity is required for the increased INF ^2 / 3 expression caused by 1 ^M CBD in adenovirus-infected cells. Data are means + / - SEM. (N=4-10).**P<0.01, ***P<0.001, ns = not significantly different. In the present case it is noted that Cannabidiol upregulates type I INF in substantial amounts. As provided in Figure 5A, from vehicle control condition (not infected with adenovirus and no treatment with Cannabidiol) to a condition where host cells are infected with adenovirus and treated with Cannabidiol, there is 8-fold increase (8 times increase) in gene expression of IFN ^ and as provided in Figure 5B from vehicle control condition (not infected with adenovirus and no treatment with Cannabidiol) to a condition where host cells are infected with adenovirus and treated with Cannabidiol, there is around 13-fold increase (13 times increase) in gene expression of IFNβ. Such enhancement in type I IFN responses to limit the proliferation and spread of DNA viruses can be mediated through cGAS system and the same shall be explored further. Thus, the present invention provides role of cannabidiol and minor cannabinoids in the prevention and treatment of interferon-responsive conditions which include without limitation treatment for various infectious diseases where disease is caused by one or more of viruses, bacteria, parasites such as protozoa, fungi, mycobacteria, etc. The role in priming host cells making them ready for attack is also established. The host cells are better able to prepare for infection including increase in the infectious dose. These actions are possible due to effects of Cannabinoids including at least one of the following, i) infected cells undergo apoptosis early after infection; ii) induction of interferon transcription; iii) induction of interferon-induced antiviral effectors. This action of Cannabidiol and minor cannabinoids can also help in multiple infections, latent or persistent infections, and to reduce or eliminate chances of mutation. The role is complimentary to vaccines or any other preventive therapy or reducing frequency of such therapy. Further Cannabinoids can be useful as a starting treatment in certain treatments when such as treatment for Tuberculosis, malaria, dengue etc. which can cause several side effects where Cannabinoids can reduce the duration of treatment or dose or both. Cannabidiols and other Cannabinoids cause substantial upregulation of IFNα, IFNβ, IFNγ, IFN ^1, and IFN ^2-3, this enhances cell immune response substantially which is unlikely to be evaded easily by pathogens. Also prompt apoptotic action may not give viruses sufficient time to evade immune response or generate variants by causing changes in RNA. Substantial upregulation of type I interferons IFNα, IFNβ establish role of Cannabidiol and Cannabinoids in treating cancers and autoimmune diseases.

[0004] Primer Sequences

[0005] Examples Western immunoblotting Methods Western immunoblots were performed as previously described by our laboratory with minor modifications. Briefly, HEK293 cells were seeded in 6 cm plates and grown for 24 hours to 80% confluence, after which they were treated with 1 ^M CBD or vehicle (0.1% ethanol) and then infected ~ 30 minutes later with adenovirus serotype 5 at a multiplicity of infection of ~1. After 24 hours, cells were harvested and washed 3x with PBS. Cells were lysed on ice using RIPA buffer solution containing 50 mM Tris-HCL, pH 8.0; 150 mM NaCl, 0.5% sodium deoxycholate, and 0.1% SDS with 10 μL / ml of protease / phosphatase inhibitor cocktail (Cell Signaling, Beverly, MA) and cleared by centrifugation at 10,000 x g for 10 min at 4 ^C. Total protein concentration from each sample was determined using a bicinchoninic acid assay (Thermo Fisher, Waltham, MA) and aliquots containing 20 μg of protein were mixed with 6 x Laemmeli Buffer (125 mM Tris-HCl, pH 6.8, 20% glycerol (v / v), 4v), 4% SDS(w / v), 10% 2-mercaptoethanol (v / v), and 0.05% bromophenol blue) and heated for 5 min at 95 ^C. The samples were electrophoresed through a 12% SDS-PAGE TGX Stain-Free™ FastCast™ gel system (Bio-Rad Canada, Mississauga, Ontario, Canada) set at 100 V for ~1.5 h, and imaged for total protein loading by visualization under UV light, then transferred onto a nitrocellulose membrane using a Bio-Rad Trans-Blot Turbo system, set at 25 V for 30 min. Membranes were blocked using 5% (w / v) Bovine Serum Albumin (BSA) in TBST (50 mM Tris-HCl, pH 7.4, 150 mM NaCl, 0.1% Tween-20) for 1 h at room temperature and then incubated overnight at 4°C in TBST containing 5% (w / v) BSA and antibodies directed against cGAS, STING, P-STING, TBK1 / NAK, and P-TBK1 / NAK (Cell Signalling, Beverly, MA). Following three TBST washes, the membranes were probed with horseradish peroxidase (HRP)-conjugated secondary antibodies (1:2000 dilutions) (Cell signalling, Beverly, MA) made in TBST with 5% BSA for 1.5 h at room temperature. Blots were washed in TBST three times and then reacted with 2 ml of Luminata Forte Chemiluminescence substrate (EMD Millipore, Etobicoke, Ontario, Canada), and imaged for immunodetectable bands using the ChemiDOC Touch Imaging system (Bio-Rad, Mississauga, Ontario, Canada). Density of bands following chemiluminescence imaging, and density of lanes following UV illumination of total protein loading in gels, were quantified using Image J Software and band densities were normalized to total protein per lane. Animal studies Animals and treatments Male C57Bl / 6J mice (~21-24 weeks of age; body weights ~38-45g) were randomly assigned to be treated for 3 days with either vehicle (sesame oil, 1 ml / kg / day, by oral gavage) or CBD (80 mg / kg / day, by oral gavage, dissolved in sesame oil carrier). On day 3, mice received their daily dose of CBD or vehicle, and then ~4 hours later, all mice were retro-orbitally injected with adenovirus (2 × 10^8 ifu / mouse). Mice continued to receive daily doses of CBD or vehicle oil by oral gavage until the end of the study. Mice from the vehicle and CBD groups were euthanized 2-, 4-, and 6-days post- infection. Brain, heart, lungs, liver, kidneys, gonadal fat and serum were harvested and flash frozen for later analysis (n=3). Genomic DNA extraction and qPCR Genomic DNA was extracted from the liver. Briefly, 1-2 mm liver tissue was incubated in an alkaline lysis buffer (95°C, 1 hour) and then an equal amount of neutralization buffer (40 mM Tris-HCl) was added to the samples. Genomic DNA was then quantified by Nanodrop, and subsequently analyzed by real time PCR (100 ng total DNA). Total levels of the viral hexon gene and mouse Pnpla2 gene were analyzed using SYBR Green. Levels of the mouse chromosomal18s gene in each sample were analyzed using a FAM-labelled primer-probe set from Applied Biosystems (Hs99999901_s1). Real-time PCR was used to measure levels of the relative number of hexon genes in mouse tissues. Hexon genes are found in the adenovirus genome, and are not normally found in mouse cells or in the mouse genome. Detection of the number of hexon DNA genes is a marker of how much virus is present in a mouse tissue, or the level of infection in a mouse tissue. Taqman real-time PCR was used to examine the total levels of 18s. This analysis was performed using the FAM-labelled primer-probe commercial assay Hs99999901_s1. This primer-probe combination amplifies and quantitatively detects DNA within a single exon, and therefore is useful for detecting the total amount of mouse chromosomal DNA in a liquid sample. This assay cannot detect adenoviral DNA, since the 18s gene is not present in the adenovirus genome. This measure was used as one of the normalization factors in our analysis. By normalizing detectable hexon gene (DNA) levels to 18s DNA levels, our measures shown reflect the amount of virus DNA present relative to mouse DNA, or the amount of virus per mouse cell. The relative number of copies of the Pnpla2 gene in each sample was measured using primers that are specific for the first exon of this gene. This assay cannot detect adenoviral DNA, since the mouse Pnpla2 gene is not present in the adenovirus genome. This measure was used as one of the normalization factors in our analysis. By normalizing detectable hexon gene (DNA) levels to mouse Pnpla2 DNA levels, our measures shown reflect the amount of virus DNA present relative to mouse DNA, or the amount of virus per mouse cell. Lentivirus Measurement of Late Apoptosis 1. HEK293 cells were seeded in 96-well plates. 2. One day later, cells were treated with vehicle 1 (0.1% ethanol) or 1 ^M CBD. 3. One hour and 30 minutes later, cells were treated with vehicle 2 (0.1% DMSO) or the RU-521 (0.8 ^M), or H-151 (1 ^M). 4. Thirty minutes later, cells were infected with lentivirus (~ 1 infectious unit per cell). 5. Twenty-four hours later, propidium iodide (a marker of late apoptosis) was added using a Kinetic Apoptosis Assay Kit from Abcam (Mississauga, Ontario, Canada), and 10 minutes later, fluorescence was read at an excitation peak of 531 nm and emission peak of 647 nm) using a BioTek Cytation 5 Cell Imaging Multimode Reader. 6. Total cells per field of view were counted under visual light BioTek Cytation 5 Cell Imaging Multimode Reader. Lentivirus imaging and cell counting 1. HEK293 cells were seeded in 96-well plates. 2. One day later, cells were treated with vehicle 1 (0.1% ethanol) or 1uM CBD. 3. In experiments where cGAS-STING pathway inhibitors were used, one hour and 30 minutes later, cells were treated with vehicle 2 (0.1% DMSO) or the RU-521 (0.8 uM), or H-151 (1 uM). 4. Thirty minutes later, cells were infected with lentivirus (~ 1 infectious unit per cell) expressing enhanced green fluorescent protein. 5. Twenty-four hours later, cells were changed to Hank’s Balanced Salt Solution, then imaged and counted under ultraviolet light to determine the number of infected cells, and imaged and counted under visible light to determine the total number of cells, using a BioTek Cytation 5 Cell Imaging Multimode Reader. Lentivirus real-time qPCR analysis HEK293 cells were seeded on a 12-well plate in 2mL media / well at a seeding density: 0.1 x 106cells / well (100,000 cells / well). One day later cells were treated with 1 ^M CBD then cGas inhibitor (RU-5210.8 µM where indicated) or STING inhibitor (H-1511 µM where indicated) or vehicle. Approximately 1 hour later, cells were infected with lentivirus (or left uninfected (mock)) at a multiplicity of infection of 1 infectious unit / cell. Twenty-four hours later total RNA was extracted using the Trizol method (500 µl Trizol / well), 2 ^g of RNA was reverse transcribed, and quantitative real-time PCR was performed using SYBR green and gene-specific primers on cDNA to assess the expression of interferons (IFN) alpha, beta, gamma, lambda 1, lambda 2-3, which were normalized to expression of GAPDH (housekeeping gene). Adenovirus imaging and cell counting 1. HEK293 cells were seeded in 96-well plates. 2. One day later, cells were treated with vehicle 1 (0.1% ethanol) or 1uM CBD. 3. In experiments where cGAS-STING pathway inhibitors were used, one hour and 30 minutes later, cells were treated with vehicle 2 (0.1% DMSO) or the RU-521 (0.8 uM), or H-151 (1 uM). 4. Thirty minutes later, cells were infected with adenovirus expressing enhanced green fluorescent protein (~ 1 infectious unit per cell). 5. Forty-eight hours later, cells were changed to Hank’s Balanced Salt Solution, then imaged and counted under ultraviolet light to determine the number of infected cells, and imaged and counted under visible light to determine the total number of cells using a BioTek Cytation 5 Cell Imaging Multimode Reader. Adenovirus real-time qPCR analysis HEK293 cells were seeded on a 12-well plate in 2mL media / well at a seeding density: 0.1 x 106cells / well (100,000 cells / well). One day later cells were treated with 1 ^M CBD then cGas inhibitor (RU-5210.8 µM where indicated) or STING inhibitor (H-1511 µM where indicated) or vehicle. Approximately 1 hour later, cells were infected with adenovirus (or left uninfected (mock)) at a multiplicity of infection of 1 infectious unit / cell. Forty-eight hours later total RNA was extracted using the Trizol method (500 µl Trizol / well), 2 ^g of RNA was reverse transcribed, and quantitative real-time PCR was performed using SYBR green and gene-specific primers on cDNA to assess the expression of interferons (IFN) alpha, beta, gamma, lambda 1, lambda 2-3, or OAS1, OAS2, OAS3 or OASL, which were normalized to expression of GAPDH (housekeeping gene). Adenovirus Measurement of Apoptosis 1. HEK293 cells were seeded in 96-well plates (10,000 cells / well). 2. One hour later, cells were treated with vehicle 1 (0.1% ethanol) or CBD as indicated. 4. Two hours later, cells were infected with adenovirus (~ 1 infectious unit per cell). 5. Twenty-four hours later, propidium iodide (a marker of late apoptosis) or pSIVA- IANBD was added to wells using a Kinetic Apoptosis Assay Kit from Abcam (Mississauga, Ontario, Canada), and 30 minutes later, fluorescence was read according to the manufacturer’s instructions using a BioTek Cytation 5 Cell Imaging Multimode Reader. 6. Total cells per field of view were counted under visual light using a BioTek Cytation 5 Cell Imaging Multimode Reader.

[0006] References Ma Z, Damania B. The cGAS-STING Defense Pathway and Its Counteraction by Viruses. Cell Host Microbe.2016;19(2):150–8. Ni G, Ma Z, Damania B. cGAS and STING: At the intersection of DNA and RNA virus-sensing networks. PLoS Pathog. 2018 Aug 16;14(8):e1007148. doi: 10.1371 / journal.ppat.1007148. PMID: 30114241; PMCID: PMC6095619. Gao D, Wu J, Wu YT, Du F, Aroh C, Yan N, et al. Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. Science. 2013;341(6148):903–6. Mankan AK, Schmidt T, Chauhan D, Goldeck M, Honing K, Gaidt M, et al. Cytosolic RNA:DNA hybrids activate the cGAS-STING axis. EMBO J. 2014;33(24):2937–46. Wu J, Chen ZJ. Innate immune sensing and signaling of cytosolic nucleic acids. Annu Rev Immunol.2014;32:461–88.10.1146 / annurev-immunol-032713-120156 . 2. Andreeva L, Hiller B, Kostrewa D, Lassig C, de Oliveira Mann CC, Jan Drexler D, et al. cGAS senses long and HMGB / TFAM-bound U-turn DNA by forming protein-DNA ladders. Nature. 2017;549(7672):394–8. 10.1038 / nature23890 . Li Y., Banerjee S., Wang Y., Goldstein S.A., Dong B., Gaughan C., Silverman R.H., Weiss S.R. Activation of RNase L is dependent on OAS3 expression during infection with diverse human viruses. Proc. Natl Acad. Sci. U.S.A. 2016; 113:2241–2246. Schwartz S.L., Conn G.L. RNA regulation of the antiviral protein 2′-5′- oligoadenylate synthetase. WIREs RNA.2019; 10: e1534. Schwartz SL, Conn GL. RNA regulation of the antiviral protein 2'-5'- oligoadenylate synthetase. Wiley Interdiscip Rev RNA.2019 Jul;10(4):e1534. doi: 10.1002 / wrna.1534. Epub 2019 Apr 15. PMID: 30989826; PMCID: PMC6585406. Meng H, Deo S, Xiong S, Dzananovic E, Donald LJ, van Dijk CW, McKenna SA. Regulation of the interferon-inducible 2'-5'-oligoadenylate synthetases by adenovirus VA(I) RNA. J Mol Biol. 2012 Oct 5;422(5):635-649. doi: 10.1016 / j.jmb.2012.06.017. Epub 2012 Jun 16. PMID: 22709583. Schneider WM, Chevillotte MD, Rice CM. Interferon-stimulated genes: a complex web of host defenses. Annu Rev Immunol.2014;32:513-545. doi:10.1146 / annurev- immunol-032713-120231 Ferguson SH, Foster DM, Sherry B, Magness ST, Nielsen DM, Gookin JL. Interferon-λ3 Promotes Epithelial Defense and Barrier Function Against Cryptosporidium parvum Infection. Cell Mol Gastroenterol Hepatol.2019;8(1):1- 20. doi: 10.1016 / j.jcmgh.2019.02.007. Epub 2019 Mar 5. PMID: 30849550; PMCID: PMC6510929. Melzer T, Duffy A, Weiss LM, Halonen SK. The gamma interferon (IFN-gamma)- inducible GTP-binding protein IGTP is necessary for toxoplasma vacuolar disruption and induces parasite egression in IFN-gamma-stimulated astrocytes. Infect Immun. 2008 Nov;76(11):4883-94. doi: 10.1128 / IAI.01288-07. Epub 2008 Sep 2. PMID: 18765738; PMCID: PMC2573374. Pinheiro RO, Rossi-Bergmann B. Interferon-gamma is required for the late but not early control of Leishmania amazonensis infection in C57Bl / 6 mice. Mem Inst Oswaldo Cruz.2007 Feb;102(1):79-82. Doi: 10.1590 / s0074-02762007000100013. PMID: 17294004. McCall MB, Sauerwein RW. Interferon-γ--central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria. J Leukoc Biol. 2010 Dec;88(6):1131-43. doi: 10.1189 / jlb.0310137. Epub 2010 Jul 7. PMID: 20610802. Travar M, Petkovic M, Verhaz A. Type I, II, and III Interferons: Regulating Immunity to Mycobacterium tuberculosis Infection. Arch Immunol Ther Exp (Warsz).2016 Feb;64(1):19-31. doi: 10.1007 / s00005-015-0365-7. Epub 2015 Sep 11. PMID: 26362801. Smith NL, Denning DW. Clinical implications of interferon-γ genetic and epigenetic variants. Immunology.2014;143(4):499-511. doi:10.1111 / imm.12362 Ding S, Li L, Zhu X. Polymorphism of the interferon-c gene and risk of tuberculosis in a southeastern Chinese population. Hum Immunol 2008; 69:129–33. Cooke GS, Campbell SJ, Sillah J et al. Polymorphism within the interferon- c / receptor complex is associated with pulmonary tuberculosis. Am J Respir Crit Care Med 2006; 174:339–43. Lio D, Marino V, Serauto A et al. Genotype frequencies of the +874T?A single nucleotide polymorphism in thefirst intron of the interferon-c gene in a sample of Sicilian patients affected by tuberculosis. Eur J Immunogenet 2002; 29:371–4. Shen C, Jiao WW, Feng WX, Wu XR, Xiao J, Miao Q et al. IFNG polymorphisms are associated with tuberculosis in Han Chinese pediatric female population. Mol Biol Rep 2013; 40:5477–82. Ansari A, Hasan Z, Dawood G, Hussain R. Differential combination of cytokine and interferon- c +874 T / A polymorphisms determines disease severity in pulmonary tuberculosis. PLoS ONE 2011; 6:e27848. Vallinoto AC, Graca ES, Araujo MS, Azevedo VN, Cayres-Vallinoto I, Machado LF, Ishak MO, Ishak R. IFNG +874T / A polymorphism and cytokine plasma levels are associated with susceptibility to Mycobacterium tuberculosis infection and clinical manifestation of tuberculosis. Hum Immunol 2010; 71:692–6. Tso HW, Ip WK, Chong WP, Tam CM, Chiang AK, Lau YL. Association of interferon c and interleukin 10 genes with tuberculosis in Hong Kong Chinese. Genes Immun 2005; 6:358–63. Sahrbacher U, Naumann L, Reischl U, Scholmerich J, Gluck T. Reduced TH-1 cytokine release in an adult patient with chronic relapsing Mycobacterium malmoense infection. Infection 2007; 35:282–6. Vankayalapati R, Wizel B, Samten B et al. Cytokine profiles in immunocompetent persons infected with Mycobacterium avium complex. J Infect Dis 2001; 183:478– 84. Storgaard M, Varming K, Herlin T, Obel N. Novel mutation in the interferon-c- receptor gene and susceptibility to mycobacterial infections. Scand J Immunol 2006; 64:137–9. Syedbasha M, Egli A. Interferon Lambda: Modulating Immunity in Infectious Diseases. Front Immunol. 2017 Feb 28;8:119. doi: 10.3389 / fimmu.2017.00119. PMID: 28293236; PMCID: PMC5328987. Wu X, Zhao Y, Gu Y, Li K, Wang X, Zhang J. Interferon-Lambda 1 Inhibits Staphylococcus aureus Colonization in Human Primary Keratinocytes. Front Pharmacol. 2021 Mar 22;12:652302. doi: 10.3389 / fphar.2021.652302. PMID: 33828484; PMCID: PMC8019897. Lan F, Zhong H, Zhang N, Johnston SL, Wen W, Papadopoulos N, Zhang L, Bachert C. IFN-λ1 enhances Staphylococcus aureus clearance in healthy nasal mucosa but not in nasal polyps. J Allergy Clin Immunol. 2019 Apr;143(4):1416- 1425.e4. doi: 10.1016 / j.jaci.2018.09.041. Epub 2018 Nov 30. PMID: 30508540. Chen SC, Korman TM, Slavin MA et al. Antifungal therapy and management of complications of cryptococcosis due to Cryptococcus gattii. Clin Infect Dis 2013; 57:543–51. Harris JR, Lindsley MD, Henchaichon S et al. High prevalence of cryptococcal infection among HIV-infected patients hospitalized with pneumonia in Thailand. Clin Infect Dis 2012; 54:e43–50. Jarvis JN, Casazza JP, Stone HH, Meintjes G, Lawn SD, Levitz SM, Harrison TS, Koup RA. The phenotype of the Cryptococcus-specific CD4+ memory T-cell response is associated with disease severity and outcome in HIV-associated cryptococcal meningitis. J Infect Dis 2013; 207:1817–28. Kelleher P, Goodsall A, Mulgirigama A, Kunst H, Henderson DC, Wilson R, Newman-Taylor A, Levin M. Interferon-gamma therapy in two patients with progressive chronic pulmonary aspergillosis. Eur Respir J. 2006 Jun;27(6):1307- 10. doi: 10.1183 / 09031936.06.00021705. PMID: 16772392. Yoshida J, Mizuno M, Wakabayashi T. Interferon-beta gene therapy for cancer: basic research to clinical application. Cancer Sci. 2004 Nov;95(11):858-65. doi: 10.1111 / j.1349-7006.2004.tb02194.x. PMID: 15546502. Gerber SA, Sedlacek AL, Cron KR, Murphy SP, Frelinger JG, Lord EM. IFN-γ mediates the antitumor effects of radiation therapy in a murine colon tumor. Am J Pathol.2013;182(6):2345-2354. doi:10.1016 / j.ajpath.2013.02.041 Kochupurakkal BS, Wang ZC, Hua T, et al. RelA-induced interferon response negatively regulates proliferation. PLoS ONE.2015;10:e0140243. Wang L, Wang Y, Song Z, Chu J, Qu X. Deficiency of interferon-gamma or its receptor promotes colorectal cancer development. J Interferon Cytokine Res. 2015;35:273-280. Li W, Huang X, Tong H, et al. Comparison of the regulation of beta-catenin signaling by type I, type II and type III interferons in hepatocellular carcinoma cells. PLoS ONE.2012;7:e47040. Stiff A, Carson W III. Investigations of interferon-lambda for the treatment of cancer. J Innate Immun. 2015;7(3):243-50. doi: 10.1159 / 000370113. Epub 2015 Feb 6. PMID: 25661266; PMCID: PMC6738825. Zhang F, Manna S, Pop LM, Chen ZJ, Fu YX, Hannan R. Type I Interferon Response in Radiation-Induced Anti-Tumor Immunity. Semin Radiat Oncol.2020 Apr;30(2):129-138. doi: 10.1016 / j.semradonc.2019.12.009. PMID: 32381292. Vlachiotis S, Andreakos E. Lambda interferons in immunity and autoimmunity. J Autoimmun. 2019 Nov;104:102319. doi: 10.1016 / j.jaut.2019.102319. Epub 2019 Aug 31. PMID: 31481283. Bourke NM, Napoletano S, Bannan C, Ahmed S, Bergin C, McKnight Á, Stevenson NJ. Control of HIV infection by IFN-α: implications for latency and a cure. Cell Mol Life Sci. 2018 Mar;75(5):775-783. doi: 10.1007 / s00018-017-2652-4. Epub 2017 Oct 7. PMID: 28988399. Ghaffarifar F, Asl AD, Sharifi Z, Ghasemi S, Solhjoo K, Mohammadi SR. The effect of betamethasone and IFN-gamma on replication of Toxoplasma gondii (RH strain) and nitric oxide production in Hela cell culture. Iran J Allergy Asthma Immunol.2006 Jun;5(2):75-8. PMID: 17237580. Wen X, Kudo T, Payne L, Wang X, Rodgers L, Suzuki Y. Predominant interferon- γ-mediated expression of CXCL9, CXCL10, and CCL5 proteins in the brain during chronic infection with Toxoplasma gondii in BALB / c mice resistant to development of toxoplasmic encephalitis. J Interferon Cytokine Res. 2010 Sep;30(9):653-60. doi: 10.1089 / jir.2009.0119. PMID: 20626297; PMCID: PMC2963637. Hong J, Tejada-Simon MV, Rivera VM, Zang YC, Zhang JZ. Anti-viral properties of interferon beta treatment in patients with multiple sclerosis. Mult Scler. 2002 May;8(3):237-42. doi: 10.1191 / 1352458502ms794oa. PMID: 12120696. Pai M, Behr M. Latent Mycobacterium tuberculosis Infection and Interferon- Gamma Release Assays. Microbiol Spectr. 2016 Oct;4(5). doi: 10.1128 / microbiolspec.TBTB2-0023-2016. PMID: 27763261. Chee CBE, Reves R, Zhang Y, Belknap R. Latent tuberculosis infection: Opportunities and challenges. Respirology. 2018 Oct;23(10):893-900. doi: 10.1111 / resp.13346. Epub 2018 Jun 14. PMID: 29901251.

Claims

Claims We claim:

1. A pharmaceutical composition comprising therapeutically effective amount of Cannabidiol for use in treating an infection in a host / patient wherein said Cannabidiol or composition thereof produces an enhancement / augmentation of innate immunity of the host / patient against said infection after activation of at least one of the following pathways, i) cGAS-STING pathway; ii) 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway; iii) Both cGAS-STING pathway and 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway; and due to one or more of the following: a) augmenting induction of interferons; b) augmenting induction of interferon stimulated factors or genes; c) by causing apoptosis of virus infected cells.

2. The pharmaceutical composition according to the claim 1 wherein an enhancement / augmentation of innate immunity of the host / patient is after activation of cGAS-STING pathway.

3. The pharmaceutical composition according to the claim 1 wherein an enhancement / augmentation of innate immunity of the host / patient is after activation of 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway.

4. The pharmaceutical composition according to the claim 1 wherein the infection in a host / patient is caused by one or more of virus, bacteria, fungi, protozoa, parasite.

5. The pharmaceutical composition according to the claim 1 wherein the infection in a host / patient is caused by one or more of the following, i) single stranded RNA viruses; ii) double stranded RNA viruses; iii) double stranded DNA viruses;iv) single stranded DNA viruses; v) DNA viruses replicated through RNA through an RNA intermediate by a reverse transcriptase.

6. The pharmaceutical composition according to the claim 1 wherein the infection in a host / patient is caused by adenovirus and / or Lentivirus.

7. The pharmaceutical composition according to the claim 1 wherein an enhancement / augmentation of innate immunity of the host / patient is due to induction of early apoptosis or late apoptosis or both early and late apoptosis of infected cells.

8. The pharmaceutical composition according to the claim 1wherein an enhancement / augmentation of innate immunity of the patient is due to induction of one or more of Type I (alpha and beta) or Type II (gamma) or Type III (lambda) Interferonsor any combination thereof.

9. The pharmaceutical composition according to the claim 1 wherein an enhancement / augmentation of innate immunity of the patient is due to induction of interferon stimulated factors or genes selected from one or more of OAS1, OAS2, OAS3, OASL.

10. A pharmaceutical composition comprising therapeutically effective amount of Cannabidiol for use in preventing an infection in a host / patient or for use in priming / preparing a host / patient for infection wherein said Cannabidiol or composition thereof produces an enhancement / augmentation of innate immunity of the host / patient against said infection after activation of at least one of the following pathways, i) cGAS-STING pathway; ii) 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway; iii) Both cGAS-STING pathway and 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway; and due to one or more of the following: a) augmenting induction of interferons; b) augmenting induction of interferon stimulated factors or genes;c) by causing apoptosis of virus infected cells.

11. A method of treating an infection in a host / patient comprising administering a pharmaceutical composition comprising therapeutically effective amount of Cannabidiol wherein said Cannabidiol or composition thereof produces an enhancement / augmentation of innate immunity of the host / patient against said infection after activation of at least one of the following pathways, i) cGAS-STING pathway; ii) 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway; iii) Both cGAS-STING pathway and 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway; and due to one or more of the following: a) augmenting induction of interferons; b) augmenting induction of interferon stimulated factors or genes; c) by causing apoptosis of virus infected cells.

12. The method according to the claim 11 wherein an enhancement / augmentation of innate immunity of the host / patient is after activation of cGAS-STING pathway .

13. The method according to the claim 11 wherein an enhancement / augmentation of innate immunity of the host / patient is after activation of 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway.

14. The method according to the claim 11 wherein the infection in a host / patient is caused by one or more of virus, bacteria, fungi, protozoa, parasite.

15. The method according to the claim 11 wherein the infection in a host / patient is caused by one or more of the following, i) single stranded RNA viruses; ii) double stranded RNA viruses; iii) double stranded DNA viruses; iv) single stranded DNA viruses;v) DNA viruses replicated through RNA through an RNA intermediate by a reverse transcriptase.

16. The method according to the claim 11 wherein the infection in a host / patient is caused by adenovirus and / or Lentivirus.

17. The method according to the claim 11 wherein an enhancement / augmentation of innate immunity of the host / patient is due to induction of early apoptosis or late apoptosis or both early and late apoptosis of infected cells.

18. The method according to the claim 11 wherein an enhancement / augmentation of innate immunity of the patient is due to induction of one or more of Type I (alpha and beta) or Type II (gamma) or Type III (lambda) Interferonsor any combination thereof.

19. The method according to the claim 11 wherein an enhancement / augmentation of innate immunity of the patient is due to induction of interferon stimulated factors or genes selected from one or more of OAS1, OAS2, OAS3, OASL.

20. A method of preventing an infection in a host / patient or method of priming / preparing a host / patient for infection comprising administering a pharmaceutical composition comprising therapeutically effective amount of Cannabidiol wherein said Cannabidiol or composition thereof produces an enhancement / augmentation of innate immunity of the host / patient against said infection after activation of at least one of the following pathways, i) cGAS-STING pathway; ii) 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway; iii) Both cGAS-STING pathway and 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway; and due to one or more of the following: a) augmenting induction of interferons; b) augmenting induction of interferon stimulated factors or genes; c) by causing apoptosis of virus infected cells.

Images