Herbal and Ayurvedic Plants as Remedial Approach for Viral Diseases with Focus on COVID-19: A Narrative Review

Background: Infectious diseases have posed a major threat to human survival for centu-ries and can devastate entire populations. Recently, the global outbreak of COVID-19 has increased exponentially, affecting more than 200 countries and millions of lives since the fall of 2019, largely due to the ineffectiveness of existing antiviral therapies. WHO announced it a public health emer-gency of international concern. A significant waiting period in antiviral therapy hindered by the rapid evolution of severe acute respiratory syndrome-coronavirus-2 aggravated the situation ensuing imposition of strict laws (e.g., communal dissociation, international travel restrictions, and mainte-nance of hygiene) that would help in inhibiting further outspread of COVID-19. Ayurveda system of medicine offers a holistic approach to the COVID-19 pandemic. Objective(s): This review aims to highlight the potential of medicinal herbs and Ayurvedic drugs as the remedial approach for viral diseases, such as COVID-19. Method(s): We reviewed the literature from journal publication websites and electronic databases, such as Bentham, Science Direct, Pub Med, Scopus, USFDA, etc. Result(s): The drugs used in the traditional system of medicine have the potential to prevent and cure the infected patient. Ayurvedic therapies are known for regulating immunity and rejuvenation properties that behold much promise in the management of COVID-19 disease. Government of India, Ministry of AYUSH recommends some precautionary fitness measures and an increase in immunity with special reference to respiratory health. Conclusion(s): While there is no medication for COVID-19 as of now, taking preventive measures and boosting body immunity is highly recommended. A number of medicinal plants that play an im-portant role in revitalizing the immune system are easily accessible in home remedies.Copyright © 2023 Bentham Science Publishers.

Molecular Modeling Targeting the ACE2 Receptor with Cannabis sativa's Active Ingredients for Antiviral Drug Discovery against SARS-CoV-2 Infections.

The emergence of a novel coronavirus that later on rendered a global pandemic, caused desperation within the communities and drove increased interest in exploring medicinal plant-based therapeutics to treat and prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infections. Many medicinal plants have been reported to have antiviral, anti-inflammatory, and immunomodulatory effects that hinder, cure, or ease the symptoms of COVID-19 infection. This exploratory study seeks to dock the active components of Cannabis sativa, a natural plant with several pharmacological and biological properties, with the angiotensin-converting enzyme II (ACE2) receptor. A total of 3 C. sativa active components have been found to bind to the ACE2 protein active site and could inhibit spike binding, although they do not compete directly with the receptor-binding domain (RBD) of SARS-CoV-2. 6-Prenylapigenin, cannabivarin (CBN-C3), and Δ8-tetrahydrocannabinolic acid-A (Δ8-THCA) have a greater affinity (-8.3, -8.3, and -8.0 kcal/mol, respectively) and satisfactory interaction with ACE2 than its inhibitor MLN-4760 (-7.1 kcal/mol). These potential drugs with higher affinity for the ACE2 receptor and adequate absorption, distribution, metabolism, excretion, and toxicity (ADMET) values are candidates for treating or preventing SARS-CoV-2 infections. In vitro and in vivo investigations are needed to evaluate further the efficacy and toxicity of these hit compounds.

2022 SAHM Annual Meeting - Caring for Adolescents in a Post-Pandemic World, Virtual, 9-12 March 2022

This journal issue includes 201 s of papers presented at the conference. Topics discussed include: association between cannabis use and COVID-19 and distress among adolescent patients;COVID-19 exposure and care-seeking behaviors among vulnerable urban adolescents and young adults;assessment of a poverty simulation in medical education;prevalence of chronic pelvic pain by sexual orientation in a large cohort of young women in the USA;confidentiality and patient satisfaction in adolescent telehealth visits;predictors of adolescent telemedicine visit no-shows during the COVID-19 pandemic;simulation of contraceptive access for adolescents using a pharmacist-staffed e-platform;foster caregivers and their role in contraception decision-making for adolescents in care.

Let's Look at Cannabis from This Angle: COVID-19

Cannabis sativa (Can nabis=hemp) contains cannabinoid-derived main components. Cannabinoids exert biological effects by stimulating cannabinoid receptors distributed throughout the body. Cannabis products affect various systems in the body such as the cardiovascular, respiratory, nervous and immune systems. They show analgesic, antiemetic, anxiolytic, antidepressant, anti-inflammatory, antimicrobial, antihypertensive, antitussive and cardioprotective effects. COVID-19 affects different organ systems in the body and causes symptoms depending on the mutation, such as dry cough, shortness of breath, nausea, vomiting, loss of appetite and sense of smell. In this article, effectiveness of C. sativa and its components on COVID-19 have been evaluated, based on the fact that components or the extracts can affect the whole body due to cannabinoid receptors. Although cannabis and its components have potential beneficial effects for the entry of COVID-19 through the receptors into the body and the symptoms, further studies are needed for their safe use. Appropriate formulation and administration routes should be determined to eliminate the side effects and risk of addiction.

Simultaneous Quantification of 17 Cannabinoids in Cannabis Inflorescence by Liquid Chromatography-Mass Spectrometry

With an increasing appreciation for the unique pharmacological properties associated with distinct, individual cannabinoids of Cannabis sativa, there is demand for accurate and reliable quantification for a growing number of them. Although recent methods are based on highly selective chromatography-mass spectrometry technology, most are limited to a few cannabinoids, while relying on unnecessarily sophisticated and expensive ultra-high performance liquid chromatography and tandem mass spectrometry. Here we report an optimised, simple extraction method followed by a reliable and simple high performance liquid chromatography method for separation. The detection is performed using a time-of-flight mass spectrometer that is available in most natural products research laboratories. Due to the simplicity of instrumentation, and the robustness resulting from a high resolution in the chromatography of isobaric cannabinoids, the method is well suited for routine phytocannabinoid analysis for a range of applications. The method was validated in terms of detection and quantification limits, repeatability, and recoveries for a total of 17 cannabinoids: detection limits were in the range 11–520 pg when using a 1 µL sample injection volume, and the recovery percentages ranged from 85% to 108%. The validated method was subsequently applied to determine cannabinoid composition in the inflorescences of several medicinal Cannabis sativa varieties.

The Role of Cannabis sativa L. as a Source of Cannabinoids against Coronavirus 2 (SARS-CoV-2): An In Silico Study to Evaluate Their Activities and ADMET Properties.

Cannabis sativa L. is an annual herbaceous plant that belongs to the family Cannabinaceae. In this study, the potential use of forty-five cannabinoids, previously identified from Cannabis sativa to alleviate COVID-19 infection via prohibition of crucial SARS-CoV-2 proteins using molecular docking, was examined. In silico studies were performed on three vital enzymes that serve as principle therapeutic targets to prevent SARS-CoV-2 replication. These enzymes are the main protease SARS-CoV-2 MPro, papain-like protease SARS-CoV-2 PLpro and angiotensin-converting enzyme 2 (ACE2). Regarding SARS-CoV-2 MPro, cannabichromanon (32) showed the best fitting within its active centers, followed by cannabinolic acid (22) and cannabinol (21), displaying ∆G of -33.63, -23.24, and -21.60 kcal/mol, respectively. Concerning SARS-CoV-2 PLpro, cannabichromanon (32) followed by cannabinolic acid (22) and cannabicyclolic acid (41) revealed the best binding within its active pockets owing to multiple bond formation with ∆G values of -28.36, -22.81, and -19.89 kcal/mol. Furthermore, cannabichromanon (32), cannabinolic acid (22), and cannabinol (21) showed considerable fitting within the active sites of angiotensin-converting enzyme 2 (ACE2) evidenced by their significant ∆G values that were estimated as -41.77, -31.34, and -30.36 kcal/mol, respectively. ADME/TOPKAT (absorption, distribution, metabolism, excretion, and toxicity) evaluation was performed on the tested cannabinoids to further explore their pharmacokinetics, pharmacodynamics, and toxicity properties. The results indicated the considerable pharmacokinetic, pharmacodynamic, and toxicity properties of cannabinol (21), cannabinolic acid (22), cannabichromanon (32), and cannabicyclolic acid (41) that showed best fitting scores within the active sites of the tested enzymes. Multivariate data analysis revealed that cannabichromanon and cannabinolic acid showed a discriminant nature and hence can be incorporated in pharmaceutical dosage forms to alleviate COVID-19 infection.

Anti-Inflammatory and Antiviral Effects of Cannabinoids in Inhibiting and Preventing SARS-CoV-2 Infection.

The COVID-19 pandemic caused by the SARS-CoV-2 virus made it necessary to search for new options for both causal treatment and mitigation of its symptoms. Scientists and researchers around the world are constantly looking for the best therapeutic options. These difficult circumstances have also spurred the re-examination of the potential of natural substances contained in Cannabis sativa L. Cannabinoids, apart from CB1 and CB2 receptors, may act multifacetedly through a number of other receptors, such as the GPR55, TRPV1, PPARs, 5-HT1A, adenosine and glycine receptors. The complex anti-inflammatory and antiviral effects of cannabinoids have been confirmed by interactions with various signaling pathways. Considering the fact that the SARS-CoV-2 virus causes excessive immune response and triggers an inflammatory cascade, and that cannabinoids have the ability to regulate these processes, it can be assumed that they have potential to be used in the treatment of COVID-19. During the pandemic, there were many publications on the subject of COVID-19, which indicate the potential impact of cannabinoids not only on the course of the disease, but also their role in prevention. It is worth noting that the anti-inflammatory and antiviral potential are shown not only by well-known cannabinoids, such as cannabidiol (CBD), but also secondary cannabinoids, such as cannabigerolic acid (CBGA) and terpenes, emphasizing the role of all of the plant's compounds and the entourage effect. This article presents a narrative review of the current knowledge in this area available in the PubMed, Scopus and Web of Science medical databases.

Detection of Eight Cannabinoids and One Tracer in Wastewater and River Water by SPE-UPLC–ESI-MS/MS

The consumption of illicit drugs represents a global social and economic problem. Using suitable analytical methods, monitoring, and detection of different illegal drugs residues and their metabolites in wastewater samples can help combat this problem. Our article defines a method to develop, validate, and practically applicate a rapid and robust analytical process for the evaluation of six naturally occurring cannabinoids (CBG, CBD, CBDV, CBN, THC, THCV), two cannabinoids in acidic form (CBDA, THCA-A), and the major cannabis-related human metabolite (THC-COOH). After SPE offline enrichment, we used a UPLC–ESI-MS/MS system, which permitted the determination of several by-products. Studied matrices were samples of different origins: (i) effluent water from a wastewater treatment plant in the Porto urban area;(ii) environmental water from Febros River, the last left-bank tributary of the Douro River. The multi-residue approach was substantiated and successfully employed to analyze the water samples collected in the above locations. The rapid and precise quantification of nine different cannabinoids in different water samples occurred within nine minutes at the ng L−1 level. The appearance of dozens of ng L−1 of some cannabis secondary metabolites, such as CBD, CBDA, CBN, THCA-A, indicates this plant species’ widespread usage among the general population in the considered area.

Targeting of Protein's Messenger RNA for Viral Replication, Assembly and Release in SARS-CoV-2 Using Whole Genomic Data From South Africa: Therapeutic Potentials of Cannabis Sativa L.

The possible evolutionary trend of COVID-19 in South Africa was investigated by comparing the genome of SARS-CoV-2 isolated from a patient in KwaZulu-Natal, South Africa with those isolated from China, Spain, Italy, and United States, as well as the genomes of Bat SARS CoV, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Mouse Hepatitis Virus (MHV), and Infectious Bronchitis Virus (IBV). Phylogenetic analysis revealed a strong homology (96%) between the genomes of SARS-CoV-2 isolated from KwaZulu-Natal, South Africa and those isolated from the study countries as well as those isolated from bat SARS CoV, MERS-CoV, MHV and IBV. The ability of phytocannabinoids from Cannabis sativa infusion to interact with gene segments (mRNAs) coding for proteins implicated in viral replication, assembly and release were also investiagted using computational tools. Hot water infusion of C. sativa leaves was freeze-dried and subjected to Gas Chromatography-Mass Spectroscopy analysis which revealed the presence of tetrahydrocannabivarin, cannabispiran, cannabidiol tetrahydrocannabinol, cannabigerol, and cannabinol. Molecular docking analysis revealed strong binding affinities and interactions between the phytocannabinoids and codon mRNAs for ORF1ab, Surface glycoprotein, Envelope protein and Nucleocapsid phosphoprotein from SARS-CoV-2 whole genome which may be due to chemico-biological interactions as a result of nucleophilic/electrophilic attacks between viral nucleotides and cannabinoids. These results depict the spread of SARS-CoV-2 is intercontinental and might have evolved from other coronaviruses. The results also portray the phytocannabinoids of C. sativa infusion as potential therapies against COVID-19 as depicted by their ability to molecularly interact with codon mRNAs of proteins implicated in the replication, translation, assembly, and release of SARS-CoV-2. However, further studies are needed to verify these activities in pre-clinical and clinical studies.

Metabolic Engineering Strategies of Industrial Hemp (Cannabis sativa L.): A Brief Review of the Advances and Challenges.

Industrial hemp (Cannabis sativa L.) is a diploid (2n = 20), dioecious plant that is grown for fiber, seed, and oil. Recently, there has been a renewed interest in this crop because of its panoply of cannabinoids, terpenes, and other phenolic compounds. Specifically, hemp contains terpenophenolic compounds such as cannabidiol (CBD) and cannabigerol (CBG), which act on cannabinoid receptors and positively regulate various human metabolic, immunological, and physiological functions. CBD and CBG have an effect on the cytokine metabolism, which has led to the examination of cannabinoids on the treatment of viral diseases, including COVID-19. Based on genomic, transcriptomic, and metabolomic studies, several synthetic pathways of hemp secondary metabolite production have been elucidated. Nevertheless, there are few reports on hemp metabolic engineering despite obvious impact on scientific and industrial sectors. In this article, recent status and current perspectives on hemp metabolic engineering are reviewed. Three distinct approaches to expedite phytochemical yield are discussed. Special emphasis has been placed on transgenic and transient gene delivery systems, which are critical for successful metabolic engineering of hemp. The advent of new tools in synthetic biology, particularly the CRISPR/Cas systems, enables environment-friendly metabolic engineering to increase the production of desirable hemp phytochemicals while eliminating the psychoactive compounds, such as tetrahydrocannabinol (THC).

Medicinal Applications of Cannabinoids Extracted from Cannabis sativa (L.): A New Route in the Fight Against COVID-19?

Cannabis sativa is a well-known plant that has been recognized for its benefits since ancient times by several medicinal systems, including those of China, India, Greece, and Egypt. Although C. sativa is one of the most investigated medicinal plants in the world, it faces some of the greatest controversies surrounding its legalization and use as a medication. C. sativa contains several hundred phytoconstituents, including the infamous "cannabinoids". It is necessary to properly understand the medicinal importance of these phytochemicals and spread awareness among the countries where cannabis is still facing legal obstacles. The current review focuses on the most recent literature pertaining to various applications of cannabinoids, with a special focus on the medicinal aspect of these phytochemicals. Peer-reviewed articles focusing on the importance of cannabis and cannabinoids are the target of this review. Articles were selected based on the relevance to the general scope of the work, i.e., application of cannabinoids. Cannabinoids can truly be regarded as wonder drugs, considering their immense diversity of usage. Unfortunately, however, many of the mares have never been researched biologically or pharmacologically due to their low yield in the plant. However, the approval of some cannabinoids by the FDA (along with other recognized national medical health systems) has opened the horizon for the use of these natural drugs in medicines such as Epidiolex® (cannabidiol, used for the treatment of severe forms of epilepsy) and Sativex®(Δ9-tetrahydrocannabinol and cannabidiol, used for the treatment of spasticity caused by multiple sclerosis). Many pharmacological properties of C. sativa are attributed to cannabidiol (CBD), a non-psychoactive component, along with Δ9-tetrahydrocannabinol (Δ9-THC), a psychoactive component. This review addresses the most important applications or current utilization of cannabinoids in a variety of treatments such as chronic pain, cancer, emesis, anorexia, irritable bowel syndrome, communicable diseases, glaucoma, and central nervous system disorders. The biosynthetic pathway of cannabinoids is also discussed. In short, cannabis has a myriad of bioactive compounds that have the potential to increase the list of approved cannabinoids suitable for therapy.