Discovery of Natural Bisbenzylisoquinoline Analogs from the Library of Thai Traditional Plants as SARS-CoV-2 3CLPro Inhibitors: In Silico Molecular Docking, Molecular Dynamics, and In Vitro Enzymatic Activity.

The emergence of SARS-CoV-2 in December 2019 has become a global issue due to the continuous upsurge in patients and the lack of drug efficacy for treatment. SARS-CoV-2 3CLPro is one of the most intriguing biomolecular targets among scientists worldwide for developing antiviral drugs due to its relevance in viral replication and transcription. Herein, we utilized computer-assisted drug screening to investigate 326 natural products from Thai traditional plants using structure-based virtual screening against SARS-CoV-2 3CLPro. Following the virtual screening, the top 15 compounds based on binding energy and their interactions with key amino acid Cys145 were obtained. Subsequently, they were further evaluated for protein-ligand complex stability via molecular dynamics simulation and binding free energy calculation using molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) approaches. Following drug-likeness and ADME/Tox assessments, seven bisbenzylisoquinolines were obtained, including neferine (3), liensinine (4), isoliensinine (5), dinklacorine (8), tiliacorinine (13), 2'-nortiliacorinine (14), and yanangcorinine (15). These compounds computationally showed a higher binding affinity than native N3 and GC-373 inhibitors and attained stable interactions on the active site of 3CLpro during 100 ns in molecular dynamics (MD) simulation. Moreover, the in vitro enzymatic assay showed that most bisbenzylisoquinolines could experimentally inhibit SARS-CoV-2 3CLPro. To our delight, isoliensinine (5) isolated from Nelumbo nucifera demonstrated the highest inhibition of protease activity with the IC50 value of 29.93 µM with low toxicity on Vero cells. Our findings suggested that bisbenzylisoquinoline scaffolds could be potentially used as an in vivo model for the development of effective anti-SARS-CoV-2 drugs.

Immune System and Epidemics: The Role of African Indigenous Bioactive Substances.

With over 6 million coronavirus pandemic deaths, the African continent reported the lowest death rate despite having a high disease burden. The African community's resilience to the pandemic has been attributed to climate and weather conditions, herd immunity, repeated exposure to infectious organisms that help stimulate the immune system, and a disproportionately large youth population. In addition, functional foods, herbal remedies, and dietary supplements contain micronutrients and bioactive compounds that can help boost the immune system. This review identified significant traditional fermented foods and herbal remedies available within the African continent with the potential to boost the immune system in epidemics and pandemics. Methodology: Databases, such as PubMed, the Web of Science, and Scopus, were searched using relevant search terms to identify traditional African fermented foods and medicinal plants with immune-boosting or antiviral capabilities. Cereal-based fermented foods, meat-, and fish-based fermented foods, and dairy-based fermented foods containing antioxidants, immunomodulatory effects, probiotics, vitamins, and peptides were identified and discussed. In addition, nine herbal remedies and spices belonging to eight plant families have antioxidant, immunomodulatory, anti-inflammatory, neuroprotective, hepatoprotective, cardioprotective, and antiviral properties. Peptides, flavonoids, alkaloids, sterols, ascorbic acid, minerals, vitamins, and saponins are some of the bioactive compounds in the remedies. Bioactive compounds in food and plants significantly support the immune system and help increase resistance against infectious diseases. The variety of food and medicinal plants found on the African continent could play an essential role in providing community resilience against infectious diseases during epidemics and pandemics. The African continent should investigate nutritional, herbal, and environmental factors that support healthy living and longevity.

Andrographis paniculata Dosage Forms and Advances in Nanoparticulate Delivery Systems: An Overview.

Andrographis paniculata is a well-known Asian medicinal plant with a major phytoconstituent of diterpene lactones, such as andrographolide, 14-deoxyandrographolide, and neoandrographolide. A World Health Organization (WHO) monograph on selected medicinal plants showed that A. paniculata extracts and its major diterpene lactones have promising anti-inflammatory, antidiabetic, antimalarial, anticancer, antifungal, antibacterial, antioxidant, and hypoglycemic activities. However, these active phytochemicals have poor water solubility and bioavailability when delivered in a conventional dosage form. These biological barriers can be mitigated if the extract or isolated compound are delivered as nanoparticles. This review discusses existing studies and marketed products of A. paniculata in solid, liquid, semi-solid, and gaseous dosage forms, either as an extract or isolated pure compounds, as well as their deficits in reaching maximum bioavailability. The pharmaceutics and pharmacological activity of A. paniculata as a nano-delivery system are also discussed.

Traditional herbs against COVID-19: back to old weapons to combat the new pandemic.

BACKGROUND: Recently, the coronavirus (COVID-19) pandemic is a chief public health disaster caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are no established effective preventive or therapeutic anti-COVID-19 drugs available except for some recently approved vaccines. Still, countless recent studies recommend various alternative and complementary approaches against COVID-19, which are medicinal herbs employed as traditional remedies to enhance immunity to struggle with viral infections. In addition, physicians worldwide are highly interested in vitamin and mineral supplements to help them combat COVID-19 either through protection or treatment. Dietary supplements specifically vitamin D, vitamin C, and zinc provide good prophylactic and therapeutic support to the presently available treatment regimens. In the present work, we have focused on plant-based remedies with promising anti-COVID-19 activities. AIM: To enable investigators and researchers to identify potential herbal compounds with anti-COVID activity to be used as promising therapies to combat this pandemic. MAIN BODY: This review highlights the recently published studies concerning natural traditional herbs, herbal bioactive metabolites, dietary supplements, and functional foods that could help prevent and/or treat COVID-19. Herein, we explored medicinal herbs as potential inhibitors of SARS-CoV-2 and discussed how these studies help form larger discussions of diet and disease. Moreover, by investigating the herbal bioactive components, we have outlined several medicinal herbs that can fight against COVID-19 by hindering SARS-CoV-2 replication and entry to its host cells, deterring the cytokine storm, and several other means. Finally, we have summarized various herbal products, functional foods, and dietary supplements with potent bioactive compounds which can inhibit and/or prevent COVID-19 disease progression. CONCLUSIONS: Based on the studies reviewed in this work, it was concluded with no doubt that phytochemical components present in various herbs could have a starring role in the deterrence and cure of coronavirus contagion.

The Efficacy of Traditional Medicinal Plants in Modulating the Main Protease of SARS-CoV-2 and Cytokine Storm.

Selected traditional medicinal plants exhibit therapeutic effects in coronavirus disease (Covid-19) patients. This review aims to identify the phytochemicals from five traditional medicinal plants (Glycyrrhiza glabra, Nigella sativa, Curcuma longa, Tinospora cordifolia and Withania somnifera) with high potential in modulating the main protease (Mpro) activity and cytokine storm in Covid-19 infection. The Mpro binding affinity of 13 plant phytochemicals were in the following order: Withanoside II>withanoside IV>withaferin A>α-hederin>withanoside V>sitoindoside IX>glabridin>liquiritigenin, nigellidine>curcumin>glycyrrhizin>tinocordiside>berberine. Among these phytochemicals, glycyrrhizin, withaferin A, curcumin, nigellidine and cordifolioside A suppressed SARS-CoV-2 replication and showed stronger anti-inflammatory activities than standard Covid-19 drugs. Both preclinical and clinical evidences supported the development of plant bioactive compounds as Mpro inhibitors.

In vitro study on efficacy of PHELA, an African traditional drug against SARS-CoV-2.

In 2019, coronavirus has made the third apparition in the form of SARS-CoV-2, a novel strain of coronavirus that is extremely pathogenic and it uses the same receptor as SARS-CoV, the angiotensin-converting enzyme 2 (ACE2). However, more than 182 vaccine candidates have been announced; and 12 vaccines have been approved for use, although, even vaccinated individuals are still vulnerable to infection. In this study, we investigated PHELA, recognized as an herbal combination of four exotic African medicinal plants namely; Clerodendrum glabrum E. Mey. Lamiaceae, Gladiolus dalenii van Geel, Rotheca myricoides (Hochst.) Steane & Mabb, and Senna occidentalis (L.) Link; as a candidate therapy for COVID-19. In vitro testing found that PHELA inhibited > 90% of SARS-CoV-2 and SARS-CoV infection at concentration levels of 0.005 mg/ml to 0.03 mg/ml and close to 100% of MERS-CoV infection at 0.1 mg/ml to 0.6 mg/ml. The in vitro average IC50 of PHELA on SARS-COV-2, SARS-CoV and MERS-COV were ~ 0.01 mg/ml. Secondly in silico docking studies of compounds identified in PHELA showed very strong binding energy interactions with the SARS-COV-2 proteins. Compound 5 showed the highest affinity for SARS-COV-2 protein compared to other compounds with the binding energy of - 6.8 kcal mol-1. Our data showed that PHELA has potential and could be developed as a COVID-19 therapeutic.

Biological Importance of a Biflavonoid 'Bilobetin' in the Medicine: Medicinal Importance, Pharmacological Activities and Analytical Aspects.

BACKGROUND: Flavonoid class phytochemicals are natural compounds present in different medicinal plants, vegetables and fruits. Ginkgo biloba contains significant amounts of bioflavonoid 'bilobetin'. Bilobetin is an active phytochemical used for the treatment of human health complications due to its medicinal properties and therapeutic benefit. The purpose of this work is to collect and reviewed scientific data on bilobetin from different literature sources; highlight their biological properties, pharmacological activities and analytical aspects. METHODS: Health beneficial aspects of bilobetin have been investigated in the present work through scientific data analysis. PubMed, Google Scholar, Google, Scopus, etc. have been searched in the present work in order to collect scientific information on bilobetin. Medicinal importance and therapeutic benefit of bilobetin has been searched in the present work through these databases of bilobetin. Detailed pharmacological activities of bilobetin have been reviewed in the present work through literature data analysis of various scientific research works. However, analytical data of bilobetin were also collected and reviewed in the present reaserch. RESULTS: Literature data analysis of bilobetin in the present work revealed the medicinal properties and therapeutic potential of bilobetin mainly due to its anti-fungal, anti-inflammatory, anti-oxidant, antihyperlipidemic, and anti-proliferative activities. Literature data analysis revealed the effectiveness of bilobetin on osteoporosis, glucose metabolism, adipocytes, SARS CoV-2, Influenza A virus and human thrombin. Scientific data also revealed the importance of different analytical techniques for the isolation, separation, identification, and quantification of bilobetin. CONCLUSION: Scientific data analysis revealed biological importance and pharmacological activities of bilobetin in the health sector.

Medicinal Herbs in the Relief of Neurological, Cardiovascular, and Respiratory Symptoms after COVID-19 Infection A Literature Review.

COVID-19 infection causes complications, even in people who have had a mild course of the disease. The most dangerous seem to be neurological ailments: anxiety, depression, mixed anxiety-depressive (MAD) syndromes, and irreversible dementia. These conditions can negatively affect the respiratory system, circulatory system, and heart functioning. We believe that phytotherapy can be helpful in all of these conditions. Clinical trials confirm this possibility. The work presents plant materials (Valeriana officinalis, Melissa officinalis, Passiflora incarnata, Piper methysticum, Humulus lupulus, Ballota nigra, Hypericum perforatum, Rhodiola rosea, Lavandula officinalis, Paullinia cupana, Ginkgo biloba, Murraya koenigii, Crataegus monogyna and oxyacantha, Hedera helix, Polygala senega, Pelargonium sidoides, Lichen islandicus, Plantago lanceolata) and their dominant compounds (valeranon, valtrate, apigenin, citronellal, isovitexin, isoorientin, methysticin, humulone, farnesene, acteoside, hypericin, hyperforin, biapigenin, rosavidin, salidroside, linalool acetate, linalool, caffeine, ginkgolide, bilobalide, mihanimbine, epicatechin, hederacoside C,α-hederine, presegenin, umckalin, 6,7,8-trixydroxybenzopyranone disulfate, fumaroprotocetric acid, protolichesteric acid, aucubin, acteoside) responsible for their activity. It also shows the possibility of reducing post-COVID-19 neurological, respiratory, and cardiovascular complications, which can affect the functioning of the nervous system.

Antiviral Plants from Marajó Island, Brazilian Amazon: A Narrative Review.

Diseases caused by viruses are a global threat, resulting in serious medical and social problems for humanity. They are the main contributors to many minor and major outbreaks, epidemics, and pandemics worldwide. Over the years, medicinal plants have been used as a complementary treatment in a range of diseases. In this sense, this review addresses promising antiviral plants from Marajó island, a part of the Amazon region, which is known to present a very wide biodiversity of medicinal plants. The present review has been limited to articles and abstracts available in Scopus, Web of Science, Science Direct, Scielo, PubMed, and Google Scholar, as well as the patent offices in Brazil (INPI), United States (USPTO), Europe (EPO) and World Intellectual Property Organization (WIPO). As a result, some plants from Marajó island were reported to have actions against HIV-1,2, HSV-1,2, SARS-CoV-2, HAV and HBV, Poliovirus, and influenza. Our major conclusion is that plants of the Marajó region show promising perspectives regarding pharmacological potential in combatting future viral diseases.

Medicinal Importance, Pharmacological Activities and Analytical Aspects of a Flavonoid Glycoside 'Nicotiflorin' in the Medicine.

BACKGROUND: Herbal products are derived from different natural sources, mainly used as a source of food material and medicine in the health sectors since ancient times. Herbal products have gained popularity in modern medicine due to their beneficial health properties and pharmacological activities. Flavonoids are an important class of secondary metabolites found to be present in medicinal plants and their derived products. Flavonoids have been known for their anti-allergic, anti-bacterial, anti-diabetic, anti-inflammatory, anti-viral, anti-proliferative, anti-mutagenic, antithrombotic, anti-carcinogenic, anti-oxidant and hepatoprotective activities in the medicine. Nicotiflorin is a flavonoidal class phytochemical, found in medicinal plants, including Traditional Chinese medicine. METHODS: Scientific data on the medicinal importance and pharmacological activities of nicotiflorin have been collected and analyzed in the present work in order to know the therapeutic importance of nicotiflorin in medicine. Scientific data have been collected from Google, Google Scholar, Science Direct, PubMed and Scopus and analyzed in the present work. Analytical techniques data of separation, isolation and identification of nicotiflorin have also been collected and presented in the current work. Further biological importance of flavonoidal class phytochemicals was also discussed in the present work to understand the biological importance of nicotiflorin in medicine as it belongs to the flavonoid class. RESULTS: Scientific data analysis revealed the therapeutic importance and pharmacological activities of nicotiflorin. Nicotiflorin has significant biological potential against coronavirus, ischemia, renal impairment, hepatic complication, memory dysfunction and myocardial infarction. The biological potential of nicotiflorin against α-glucosidase and α-amylase enzymes, multiple myeloma cells and insulin secretion has also been discussed in the present work. Analytical data revealed the significance of modern analytical tools in medicine for the isolation, separation and quantification of nicotiflorin. CONCLUSION: Scientific data analysis of different research works revealed the biological importance and therapeutic potential of nicotiflorin in medicine.

COVID-19: an In Silico Analysis on Potential Therapeutic Uses of Trikadu as Immune System Boosters.

Corona virus pandemic outbreak also known as COVID-19 has created an imbalance in this world. Scientists have adopted the use of natural or alternative medicines which are consumed mostly as dietary supplements to boost the immune system as herbal remedies. India is famous for traditional medicinal formulations which includes 'Trikadu'-a combination of three acrids, namely Zingiber officinale, Piper nigrum and Piper longum which have antioxidant properties that boost our immune system hence acting as a strong preventive measure. In this study, AutoDock 4.0 was used to study interaction between the phytocompounds of Trikadu with RNA-dependent polymerase protein and enveloped protein of the SARS-CoV-2 virus. Analysis of the results showed that coumarin, coumaperine and bisdemethoxycurcumin showed strong bonding interactions with both the proteins. We can conclude that Trikadu has the potential molecules; hence, it can be incorporated in the diet to boost the immune system as a preventive measure against the virus.

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

In late 2019, COVID-19 emerged in Wuhan, China. Currently, it is an ongoing global health threat stressing the need for therapeutic compounds. Linking the virus life cycle and its interaction with cell receptors and internal cellular machinery is key to developing therapies based on the control of infectivity and inflammation. In this framework, we evaluate the combination of cannabidiol (CBD), as an anti-inflammatory molecule, and terpenes, by their anti-microbiological properties, in reducing SARS-CoV-2 infectivity. Our group settled six formulations combining CBD and terpenes purified from Cannabis sativa L, Origanum vulgare, and Thymus mastichina. The formulations were analyzed by HPLC and GC-MS and evaluated for virucide and antiviral potential by in vitro studies in alveolar basal epithelial, colon, kidney, and keratinocyte human cell lines. Conclusions and Impact: We demonstrate the virucide effectiveness of CBD and terpene-based formulations. F2TC reduces the infectivity by 17%, 24%, and 99% for CaCo-2, HaCat, and A549, respectively, and F1TC by 43%, 37%, and 29% for Hek293T, HaCaT, and Caco-2, respectively. To the best of our knowledge, this is the first approach that tackles the combination of CBD with a specific group of terpenes against SARS-CoV-2 in different cell lines. The differential effectiveness of formulations according to the cell line can be relevant to understanding the pattern of virus infectivity and the host inflammation response, and lead to new therapeutic strategies.

Prevention, treatment and potential mechanism of herbal medicine for Corona viruses: A review.

The pandemic of coronavirus disease 2019 (COVID-19) caused by the SARS-coronavirus 2(SARS-CoV-2) virus has become the greatest global public health crisis in recent years,and the COVID-19 epidemic is still continuing. However, due to the lack of effectivetherapeutic drugs, the treatment of corona viruses is facing huge challenges. In thiscontext, countries with a tradition of using herbal medicine such as China have beenwidely using herbal medicine for prevention and nonspecific treatment of corona virusesand achieved good responses. In this review, we will introduce the application of herbalmedicine in the treatment of corona virus patients in China and other countries, andreview the progress of related molecular mechanisms and antiviral activity ingredients ofherbal medicine, in order to provide a reference for herbal medicine in the treatment ofcorona viruses. We found that herbal medicines are used in the prevention and fightagainst COVID-19 in countries on all continents. In China, herbal medicine has beenreported to relieve some of the clinical symptoms of mild patients and shorten the length of hospital stay. However, as most herbal medicines for the clinical treatment of COVID-19still lack rigorous clinical trials, the clinical and economic value of herbal medicines in theprevention and treatment of COVID-19 has not been fully evaluated. Future work basedon large-scale randomized, double-blind clinical trials to evaluate herbal medicines andtheir active ingredients in the treatment of new COVID-19 will be very meaningful.

Indian spices: past, present and future challenges as the engine for bio-enhancement of drugs: impact of COVID-19.

Spices are natural plant products enriched with the history of being used as herbal medicine for prevention of diseases. India is also known as the 'Land of Spices'. Out of 109 spices recognized by the International Organization for Standardization (ISO) more than 52-60 spice crops are grown in India. The major spices exported by India are turmeric, cumin, coriander, fenugreek, peppers, etc. The Indian spices are divided into three era viz. early period, middle age and early modern period. Spices are used in beverages, liquors, and pharmaceutical, cosmetic and perfumery products. The major issue with spices is their handling and storage. This review article mainly focuses on two aspects: at the outset the handling and storage of the spices is an essential factor as spices are available in different forms like raw, processed, fresh, whole dried, or pre-ground dried. Therefore, the need of processing, packaging, storage and handling of the spices is important as the deterioration of spices can lead to the loss of therapeutic activity. Furthermore, many herbal constituents have the capability to enhance the bioavailability of drugs. Therefore, an attempt has been made to throw a light on the bioenhancer activity and therapeutic activity along with their mechanism of action of some Indian spices which are regularly used for cooking purpose on a daily basis to enhance the taste of food. The spices suggested by ministry of AYUSH which is relevant to its medicinal and biological property in treatment and prevention from COVID-19 are discussed. © 2022 Society of Chemical Industry.

Can Artemisia herba-alba Be Useful for Managing COVID-19 and Comorbidities?

The focus of this roadmap is to evaluate the possible efficacy of Artemisia herba-alba Asso. (Asteraceae) for the treatment of COVID-19 and some of its symptoms and several comorbidities using a combination of in silico (molecular docking) studies, reported ethnic uses, and pharmacological activity studies of this plant. In this exploratory study, we show that various phytochemicals from Artemisia herba-alba can be useful against COVID-19 (in silico studies) and for its associated comorbidities. COVID-19 is a new disease, so reports of any therapeutic treatments against it (traditional or conventional) are scanty. On the other hand, we demonstrate, using Artemisia herba-alba as an example, that through a proper search and identification of medicinal plant(s) and their phytochemicals identification using secondary data (published reports) on the plant's ethnic uses, phytochemical constituents, and pharmacological activities against COVID-19 comorbidities and symptoms coupled with the use of primary data obtained from in silico (molecular docking and molecular dynamics) studies on the binding of the selected plant's phytochemicals (such as: rutin, 4,5-di-O-caffeoylquinic acid, and schaftoside) with various vital components of SARS-CoV-2, it may be possible to rapidly identify plants that are suitable for further research regarding therapeutic use against COVID-19 and its associated symptoms and comorbidities.

Molecular Mechanisms of Possible Action of Phenolic Compounds in COVID-19 Protection and Prevention.

The worldwide outbreak of COVID-19 was caused by a pathogenic virus called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Therapies against SARS-CoV-2 target the virus or human cells or the immune system. However, therapies based on specific antibodies, such as vaccines and monoclonal antibodies, may become inefficient enough when the virus changes its antigenicity due to mutations. Polyphenols are the major class of bioactive compounds in nature, exerting diverse health effects based on their direct antioxidant activity and their effects in the modulation of intracellular signaling. There are currently numerous clinical trials investigating the effects of polyphenols in prophylaxis and the treatment of COVID-19, from symptomatic, via moderate and severe COVID-19 treatment, to anti-fibrotic treatment in discharged COVID-19 patients. Antiviral activities of polyphenols and their impact on immune system modulation could serve as a solid basis for developing polyphenol-based natural approaches for preventing and treating COVID-19.

Andrographolide: A Herbal-Chemosynthetic Approach for Enhancing Immunity, Combating Viral Infections, and Its Implication on Human Health.

Plants consistently synthesize and accumulate medically valuable secondary metabolites which can be isolated and clinically tested under in vitro conditions. An advancement with such important phytochemical production has been recognized and utilized as herbal drugs. Bioactive andrographolide (AGL; C20H30O5) isolated from Andrographis paniculate (AP) (Kalmegh) is a diterpenoid lactones having multifunctional medicinal properties including anti-manic, anti-inflammatory, liver, and lung protective. AGL is known for its immunostimulant activity against a variety of microbial infections thereby, regulating classical and alternative macrophage activation, Ag-specific antibody production during immune disorder therapy. In vitro studies with AGL found it to be effective against multiple tumors, neuronal disorders, diabetes, pneumonia, fibrosis, and other diverse therapeutic misadventures. Generally, virus-based diseases like ZIKA, influenza A virus subtype (H1NI), Ebola (EBOV), Dengue (DENV), and coronavirus (COVID-19) epidemics have greatly increased scientific interest and demands to develop more effective and economical immunomodulating drugs with minimal side effects. Trials and in vitro pharmacological studies with AGL and medicinally beneficial herbs might contribute to benefit the human population without using chemical-based synthetic drugs. In this review, we have discussed the possible role of AGL as a promising herbal-chemo remedy during human diseases, viral infections and as an immunity booster.

Exploring Phytochemicals from Himalayan Medicinal Plants as Novel Therapeutic Agents.

Over-prescription of medicines leads to some crucial health issues like resistance, non-specificity, etc. Therefore, a human consumes various natural foods, therapeutics, and nutritional supplements to combat this problem. Various therapeutic properties of secondary metabolites, such as anticancer, anti-inflammatory, and antibacterial properties, are important in drug discovery and medicinal application. These natural products have replaced synthetic materials, resulting in a great deal of sustainability, rational use, and preservation of biodiversity. This review described the potential therapeutic applications of secondary plant metabolites found in Himalayan Indian plants. The database contains 45 plants to treat various diseases, such as cancer, inflammation, and microbial infections. Besides authorized ITIS names, it includes Hindi names, family names, and active constituents. The most important information about the molecules can be found in the hyperlinks for the active constituents. It includes structures (two-dimensional and threedimensional), names and identifiers, chemical and physical properties, spectral information, biochemistry, literature and patents. The review also references various phytochemicals responsible for preventing COVID-19. Despite several challenges in manufacturing natural products, researchers may conduct research to produce successful medicines with few side effects.

The first report of iron-rich population of adapted medicinal spinach (Blitum virgatum L.) compared with cultivated spinach (Spinacia oleracea L.).

Folk medicine such as herbal and natural products have been used for centuries in every culture throughout the world. The Chenopodiaceae family with more than 1500 species is dispersed worldwide. The Iranian wild spinach (Blitum virgatum L.) is an important traditional medicinal plant used for antiviral diseases such as pneumonia and other respiratory track infections. This plant is a mountainous herb and is growing upper than 3000 m. We performed a mass selection plant breeding program on wild populations of this Iranian wild spinach during 2013-2020. Based on experimental and field characteristics this plant was identified as B. virgatum, |abbaricum|, and related characteristics were prepared with reference to the International Union for the Protection of New Varieties of Plants (UPOV). Mass selection program resulted from an adapted population named as medicinal spinach (MSP) population. To compare the mineral content of the mass-selected population with cultivated spinach (Spinacia oleracea L. |Varamin 88|), both plants were planted in pots and fields under similar conditions. In five leaves stage, plant samples were taken from both leaf and crown sections and used for experimental analysis. Atomic absorption spectroscopy was used to determine the mineral content including iron (Fe), zinc (Z), manganese (Mn), and copper (Cu). Our results showed the selected medicinal spinach population (MSP) with about 509 ppm iron was an important iron-rich population with about 3.5-4 times more than the amount of iron in cultivated spinach in the same conditions. Because iron is an important essential element for blood production, respiration process, energy metabolisms, synthesis of collagen, and some neurotransmitters are needed for proper immune function, so the supply of absorbable adequate iron is very important. The reasons such as the prevalence of the COVID-19 pandemic, which affects the amount of exchangeable oxygen in the lungs and historical local evidences of the use of this plant (MSP) for pneumonia, could open new horizons for focusing on studies related to the use of ancestral human experiences in addition to scientifically modern research.

Jeopardy of COVID-19: Rechecking the Perks of Phytotherapeutic Interventions.

The novel coronavirus disease (COVID-19), the reason for worldwide pandemic, has already masked around 220 countries globally. This disease is induced by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Arising environmental stress, increase in the oxidative stress level, weak immunity and lack of nutrition deteriorates the clinical status of the infected patients. Though several researches are at its peak for understanding and bringing forward effective therapeutics, yet there is no promising solution treating this disease directly. Medicinal plants and their active metabolites have always been promising in treating many clinical complications since time immemorial. Mother nature provides vivid chemical structures, which act multi-dimensionally all alone or synergistically in mitigating several diseases. Their unique antioxidant and anti-inflammatory activity with least side effects have made them more effective candidate for pharmacological studies. These medicinal plants inhibit attachment, encapsulation and replication of COVID-19 viruses by targeting various signaling molecules such as angiotensin converting enzyme-2, transmembrane serine protease 2, spike glycoprotein, main protease etc. This property is re-examined and its potency is now used to improve the existing global health crisis. This review is an attempt to focus various antiviral activities of various noteworthy medicinal plants. Moreover, its implications as prophylactic or preventive in various secondary complications including neurological, cardiovascular, acute kidney disease, liver disease are also pinpointed in the present review. This knowledge will help emphasis on the therapeutic developments for this novel coronavirus where it can be used as alone or in combination with the repositioned drugs to combat COVID-19.