Phytochemicals: an immune booster against the pathogens

Phytochemicals are chemical compounds produced by plants. Actually, it is produced by primary and secondary metabolism. Vegetables, fruits, whole grains, nuts, seeds, etc., are rich with phytochemicals and impart aroma, colors, and flavors. There are many phytochemicals like polyphenols, flavonoids, carotenoids, phytoestrogens, phytosterols, etc. They act as antioxidants against diseases related to lungs, urinal, stomach, and heart and can be used as nutraceuticals to control various metabolic disorders. Medicinal plants have been regarded as beneficial for many centuries. In India, Himalayas and Western Ghat regions are diverse in such plants. It has many beneficial effects on human health and boosts up immunity. Tens of thousands of phytochemicals have been identified, and many more are yet to be discovered. Synthetic medicine is known to cause many side effects on human health, and having such natural medicinal plants in diet is believed to be beneficial without side effects. They may increase immunity to fight against today's diseases like SARS, MERS, and Coronavirus (CoV) infections. The phytotherapy or the phytomedicines are effective immunity boosters and have the potential to eliminate bacterial as well as viral infections. Phytochemicals like phenolic compounds, vegetables, and fruits containing such compounds in the human diet may be effective against coronaviruses and people cure due to having it in their diet too. Still more research and identification of such compounds are required to get more information regarding its benefits. The phytotherapy-based research and developing phytotherapic medicines could cure many more chronic as well as acute diseases. This chapter deals with comprehensive information on phytochemicals and its importance. © 2023 Elsevier Inc. All rights reserved.

Medicinal Plants used Traditionally in Sudan to Treat Viral Infections Related to the Signs and Symptoms of COVID-19: A Systematic Review

Background: The rapid global spread of the COVID-19 pandemic urged scientists to search for effective and safe anti-coronavirus drugs from natural resources. Through centuries, traditional medicinal plants have been providing cure for diseases and general health care worldwide. Objective(s): The main aim of this review was to explore and summarize the research works on the different plants used traditionally in Sudan to treat signs and symptoms of COVID-19 and respiratory diseases, characterizing their antiviral activities and exploring the different phytochemicals present in these plants. Method(s): The current review was carried out in line with the recommendations of the PRISMA 2020 statement. Information on plants traditionally used in Sudan to treat the signs and symptoms of COVID-19 and respiratory diseases was obtained from traditional medicine books and published articles, as well as the daily practice by ordinary people. Result(s): This article illustrated the use of 27 plant species belonging to 15 families in Sudanese traditional medicine to treat signs and symptoms of COVID-19 and respiratory diseases. Legumi-nosae/Fabaceae was found to be the most represented family (7 species), followed by Combretaceae (3 species) and Capparidaceae and Malvaceae (2 species each). From these plants, about 11 plant species were studied for their antiviral activity against at least one virus, and 5 plants, namely Adan-sonia digitata, Boscia senegalensis, Hibiscus sabdariffa, Nigella sativa, and Mangifera indica, were tested for their antiviral activity against influenza viruses. The phytoconstituents of the listed plants were summarized, and the antiviral activity of their isolated bioactive compounds was highlighted. Conclusion(s): The review could provide an in-depth theoretical basis and valuable data for designing future studies.Copyright © 2023 Bentham Science Publishers.

PHARMACOLOGICAL POTENTIAL OF POLYHERBAL FORMULATION KABASURA KUDINEER: A REVIEW

Diabetes is a long-term medical condition in which the body has difficulty converting food into energy. High blood glucose levels are produced by poor glucose management, which alters the overall metabolic process of the body. The accumulation of abnormal (excess) blood glucose and the inability to metabolize plasma glucose causes lethal damage to the body's major organs or organ systems such as heart disease, nephropathy, retinal degeneration, sensory loss, and even premature death. Despite the administration of long-term medications, available diabetes mellitus therapy is unable to cure and unable to prevent patients from key organ damage. Diabetics have a significant financial burden, in addition to drug-drug interactions. A tremendous amount of data and proof has been amassed, proving medicinal plants' enormous potential. Plants are a naturally occurring source of therapeutic strategy for mankind. In accordance with the literature review, people who have metabolic syndrome are more likely to contract COVID-19. To overcome pandemics, we need efficient and effective herbal management. Kabasurakudineer is a polyherbal formulation that is gaining acceptance in the medical world. It may have a synergistic impact that is advantageous in the therapy of metabolic illnesses such as diabetes. Type 2 diabetes is expected to affect 640 million people by 2040, with 70% of those affected being hypertensive and predisposed to obesity and dyslipidemia. © 2023, Rasayan Journal of Chemistry, c/o Dr. Pratima Sharma. All rights reserved.

Perspectives on plant flavonoid quercetin-based drugs for novel SARS-CoV-2.

BACKGROUND: The world pandemic COVID-19 caused by SARS-CoV-2 is currently claiming thousands of lives. Flavonoids abundantly present in the fruits and vegetables, especially quercetin, are shown to have antiviral activities. MAIN TEXT: This paper reviews the capability of the plant flavonoid quercetin to fight the novel coronavirus and the possibility for drug development based on this. The mode of action explaining the known pathways through which this molecule succeeds in the antiviral activity, action of quercetin on SARS-CoV-2 main protease 3CLpro, antiviral activities of its derivatives on human viruses, effect of combination of zinc co-factor along with quercetin in the COVID-19 treatment, and the regulation of miRNA genes involved in the viral pathogenesis are discussed. Proof for this concept is provided following the virtual screening using ten key enzymes of SARS-CoV-2 and assessing their interactions. Active residues in the 3D structures have been predicted using CASTp and were docked against quercetin. Key proteins 3CLpro, spike glycoprotein/ human ACE2-BOAT1 complex, RNA-dependent RNA polymerase, main peptidase, spike glycoprotein, RNA replicase, RNA binding protein, papain-like protease, SARS papain-like protease/ deubiquitinase, and complex of main peptidase with an additional Ala at the N-terminus of each protomer, have shown the binding energies ranging between - 6.71 and - 3.37 kcal/ Mol, showing that quercetin is a potential drug candidate inhibiting multiple SARS-CoV-2 enzymes. CONCLUSION: The antiviral properties of flavonoid and the molecular mechanisms involved are reviewed. Further, proof for this concept is given by docking of key proteins from SARS-CoV-2 with quercetin.

In silico screening of phytopolyphenolics for the identification of bioactive compounds as novel protease inhibitors effective against SARS-CoV-2.

Due to the unavailability specific drugs or vaccines (FDA approved) that can cure COVID-19, the development of potent antiviral drug candidates/therapeutic molecules against COVID-19 is urgently required. This study was aimed at in silico screening and study of polyphenolic phytochemical compounds in a rational way by virtual screening, molecular docking and molecular dynamics studies against SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro) enzymes. The objective of the study was to identify plant-derived polyphenolic compounds and/or flavonoid molecules as possible antiviral agents with protease inhibitory potential against SARS-CoV-2. In this study, we report plant-derived polyphenolic compounds (including flavonoids) as novel protease inhibitors against SARS-CoV-2. From virtual docking and molecular docking study, 31 polyphenolic compounds were identified as active antiviral molecules possessing well-defined binding affinity with acceptable ADMET, toxicity and lead-like or drug-like properties. Six polyphenolic compounds, namely, enterodiol, taxifolin, eriodictyol, leucopelargonidin, morin and myricetin were found to exhibit remarkable binding affinities against the proteases with taxifolin and morin exhibiting the highest binding affinity toward Mpro and PLpro respectively. Molecular dynamics simulation studies of these compounds in complex with the proteases showed that the binding of the compounds is characterized by structural perturbations of the proteases suggesting their antiviral activities. These compounds can therefore be investigated further by in vivo and in vitro techniques to assess their potential efficacy against SARS-CoV-2 and thus serve as the starting point for the development of potent antiviral agents against the deadly COVID-19.Communicated by Ramaswamy H. Sarma.

Insights into the Pharmacological Effects of Flavonoids: The Systematic Review of Computer Modeling.

Computer modeling is a method that is widely used in scientific investigations to predict the biological activity, toxicity, pharmacokinetics, and synthesis strategy of compounds based on the structure of the molecule. This work is a systematic review of articles performed in accordance with the recommendations of PRISMA and contains information on computer modeling of the interaction of classical flavonoids with different biological targets. The review of used computational approaches is presented. Furthermore, the affinities of flavonoids to different targets that are associated with the infection, cardiovascular, and oncological diseases are discussed. Additionally, the methodology of bias risks in molecular docking research based on principles of evidentiary medicine was suggested and discussed. Based on this data, the most active groups of flavonoids and lead compounds for different targets were determined. It was concluded that flavonoids are a promising object for drug development and further research of pharmacology by in vitro, ex vivo, and in vivo models is required.

Thuja Occidentalis: an Unexplored Phytomedicine with Therapeutic Applications.

BACKGROUND: The current outbreak of respiratory disease due to SARS-CoV-2 has received global attention, and recent studies show various limitations, including treatment. Phytomedicine has played a prominent role in the treatment and prevention of various epidemic and pandemic diseases. OBJECTIVE: Here, we attempt to focus on a safe and feasible approach for Thuja occidentalis to manage and alleviate the panic of respiratory viral infection infections including COVID-19 by strengthening an individual's immunity. The relevant information was collected from the web-based databases Pubmed, Google Scholar, and MEDLINE as well as internet sources. CONCLUSION: As an important phytomedicine and king of antipsychotics, T. occidentalis possesses a plethora of immunological properties that not only can be used effectively in the management of respiratory viral infection infections, but also have the potential to prevent the further progression of the disease. Importantly, this is only part of the approach to treatment for the current outbreak that should be considered along with other measures.

Randomized double-blind clinical study in patients with COVID-19 to evaluate the safety and efficacy of a phytomedicine (P2Et).

Background: It has been proposed that polyphenols can be used in the development of new therapies against COVID-19, given their ability to interfere with the adsorption and entrance processes of the virus, thus disrupting viral replication. Seeds from Caesalpinia spinosa, have been traditionally used for the treatment of inflammatory pathologies and respiratory diseases. Our team has obtained an extract called P2Et, rich in polyphenols derived from gallic acid with significant antioxidant activity, and the ability to induce complete autophagy in tumor cells and reduce the systemic inflammatory response in animal models. Methods: In this work, a phase II multicenter randomized double-blind clinical trial on COVID-19 patients was designed to evaluate the impact of the P2Et treatment on the clinical outcome and the immunological parameters related to the evolution of the disease. The Trial was registered with the number No. NCT04410510*. A complementary study in an animal model of lung fibrosis was carried out to evaluate in situ lung changes after P2Et in vivo administration. The ability of P2Et to inhibit the viral load of murine and human coronaviruses in cellular models was also evaluated. Results: Patients treated with P2Et were discharged on average after 7.4 days of admission vs. 9.6 days in the placebo group. Although a decrease in proinflammatory cytokines such as G-CSF, IL-15, IL-12, IL-6, IP10, MCP-1, MCP-2 and IL-18 was observed in both groups, P2Et decreased to a greater extent G-CSF, IL-6 and IL-18 among others, which are related to lower recovery of patients in the long term. The frequency of T lymphocytes (LT) CD3+, LT double negative (CD3+CD4-CD8-), NK cells increased in the P2Et group where the population of eosinophils was also significantly reduced. In the murine bleomycin model, P2Et also reduced lung inflammation and fibrosis. P2Et was able to reduce the viral replication of murine and human coronaviruses in vitro, showing its dual antiviral and anti-inflammatory role, key in disease control. Conclusions: Taken together these results suggest that P2Et could be consider as a good co-adjuvant in the treatment of COVID-19. Clinical trail registration: https://clinicaltrials.gov/ct2/show/NCT04410510, identifier: NCT04410510.

Role of ethno-phytomedicine knowledge in healthcare of COVID-19: advances in traditional phytomedicine perspective.

Background: Since the outbreak of the COVID-19 virus, ethnomedicinal plants have been used in diverse geographical locations for their purported prophylactic and pharmacological effects. Medicinal plants have been relied on by people around the globe for centuries, as 80% of the world's population rely on herbal medicines for some aspect of their primary health care needs, according to the World Health Organization. Main body: This review portrays advances in traditional phytomedicine by bridging the knowledge of ethno-phytomedicine and COVID-19 healthcare. Ethnomedicinal plants have been used for symptoms related to COVID-19 as antiviral, anti-infective, anti-inflammatory, anti-oxidant, antipyretic, and lung-gut immune boosters. Traditionally used medicinal plants have the ability to inhibit virus entry and viral assembly, bind to spike proteins, membrane proteins, and block viral replications and enzymes. The efficacy of traditional medicinal plants in the terms of COVID-19 management can be evaluated by in vitro, in vivo as well as different in silico techniques (molecular docking, molecular dynamics simulations, machine learning, etc.) which have been applied extensively to the quest and design of effective biotherapeutics rapidly. Other advances in traditional phytomedicines against COVID-19 are controlled clinical trials, and notably the roles in the gut microbiome. Targeting the gut microbiome via medicinal plants as prebiotics is also found to be an alternative and potential strategy in the search for a COVID-19 combat strategy. Conclusions: Since medicinal plants are the sources of modern biotherapeutics development, it is essential to build collaborations among ethnobotanists, scientists, and technologists toward developing the most efficient and the safest adjuvant therapeutics against the pandemic of the twenty-first century, COVID-19.

A Comparative Photographic Review on Higher Plants and Macro-Fungi: A Soil Restoration for Sustainable Production of Food and Energy

The Kingdom of Plantae is considered the main source of human food, and includes several edible and medicinal plants, whereas mushrooms belong to the Kingdom of fungi. There are a lot of similar characteristics between mushrooms and higher plants, but there are also many differences among them, especially from the human health point of view. The absences of both chlorophyll content and the ability to form their own food are the main differences between mushrooms and higher plants. The main similar attributes found in both mushrooms and higher plants are represented in their nutritional and medicinal activities. The findings of this review have a number of practical implications. A lot of applications in different fields could be found also for both mushrooms and higher plants, especially in the bioenergy, biorefinery, soil restoration, and pharmaceutical fields, but this study is the first report on a comparative photographic review between them. An implication of the most important findings in this review is that both mushrooms and plants should be taken into account when integrated food and energy are needed. These findings will be of broad use to the scientific and biomedical communities. Further investigation and experimentation into the integration and production of food crops and mushrooms are strongly recommended under different environmental conditions, particularly climate change.

Potential roles of phytochemicals in combating severe acute respiratory syndrome Coronavirus infection

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of the current ongoing global pandemic COVID-19 is yet far away from the clutches of contemporary western medicines. With the lack of conventional drugs for this deadly disease the scope for the development of herbal formulations and Ayurvedic medication is finding a sound basis in the current scenario. The past two years has witnessed detailed and focused investigations on the biologically active constituents derived from a range of medicinal plants and their potential antiviral properties against SARSCoV-2. The promising results of these investigations have intrigued the medical and plant experts in pharmacognosy enough to consider herbal medicines and plant-based products as they are more effective in combating the COVID-19 crisis. However, a large-scale application of the same would require more focused and thorough research on this matter. This review is an attempt to describe the current and future prospects of using medicinal plants and herbal compounds as natural and sustainable alternative for treating COVID-19. The current article evaluates the various strong evidences from biochemical and molecular studies that have been investigated so far for the development of herbal formulations to combat COVID-19 with detailed focus on the most potential phytochemicals of medicinal plants studied in this regard namely, Withania somnifera (L.) Dunal, Cinchona officinalis L., Curcuma longa L., Ocimum sanctum L., Azadirachta indica A. Juss. and Tinospora cordifolia (Willd.) Miers.

Efficacy and Safety of Complementary Therapy With Jing Si Herbal Tea in Patients With Mild-To-Moderate COVID-19: A Prospective Cohort Study.

Background: Since late 2019, there has been a global COVID-19 pandemic. To preserve medical capacity and decrease adverse health effects, preventing the progression of COVID-19 to severe status is essential. Jing-Si Herbal Tea (JSHT), a novel traditional Chinese medicine formula was developed to treat COVID-19. This study examined the clinical efficacy and safety of JSHT in patients with mild-to-moderate COVID-19. Methods: In this prospective cohort study, we enrolled 260 patients with mild-to-moderate COVID-19. The enrolled patients were divided into the JSHT (n = 117) and control (n = 143) groups. Both groups received standard management. The JSHT group was treated with JSHT as a complementary therapy. Results: Compared with standard management alone, JSHT combined with standard management more effectively improved the reverse transcription-polymerase chain reaction cycle threshold value, C-reactive protein level, and Brixia score in the adult patients with mild-to-moderate COVID-19, especially in the male and older patients (those aged ≥60 years). The results revealed that the patients treated with JSHT combined with standard management had 51, 70, and 100% lower risks of intubation, Medisave Care Unit admission, and mortality compared with those receiving standard management only. Conclusions: JSHT combined with standard management more effectively reduced the SARS-CoV-2 viral load and systemic inflammation and alleviated lung infiltrates in the patients with mild-to-moderate COVID-19, especially in the male and older patients (those aged ≥60 years). JSHT combined with standard management may prevent critical status and mortality in patients with mild-to-moderate COVID-19. JSHT is a promising complementary therapy for patients with mild-to-moderate COVID-19.

Repurposing of phytomedicine-derived bioactive compounds with promising anti-SARS-CoV-2 potential: Molecular docking, MD simulation and drug-likeness/ADMET studies.

In view of the potential of traditional plant-based remedies (or phytomedicines) in the management of COVID-19, the present investigation was aimed at finding novel anti-SARS-CoV-2 molecules by in silico screening of bioactive phytochemicals (database) using computational methods and drug repurposing approach. A total of 160 compounds belonging to various phytochemical classes (flavonoids, limonoids, saponins, triterpenoids, steroids etc.) were selected (as initial hits) and screened against three specific therapeutic targets (Mpro/3CLpro, PLpro and RdRp) of SARS-CoV-2 by docking, molecular dynamics simulation and drug-likeness/ADMET studies. From our studies, six phytochemicals were identified as notable ant-SARS-CoV-2 agents (best hit molecules) with promising inhibitory effects effective against protease (Mpro and PLpro) and polymerase (RdRp) enzymes. These compounds are namely, ginsenoside Rg2, saikosaponin A, somniferine, betulinic acid, soyasapogenol C and azadirachtin A. On the basis of binding modes and dynamics studies of protein-ligand intercations, ginsenoside Rg2, saikosaponin A, somniferine were found to be the most potent (in silico) inhibitors potentially active against Mpro, PLpro and RdRp, respectively. The present investigation can be directed towards further experimental studies in order to confirm the anti-SARS-CoV-2 efficacy along with toxicities of identified phytomolecules.

Antiviral and Immunomodulatory Effects of Pelargonium sidoides DC. Root Extract EPs® 7630 in SARS-CoV-2-Infected Human Lung Cells.

Treatment options for COVID-19 are currently limited. Drugs reducing both viral loads and SARS-CoV-2-induced inflammatory responses would be ideal candidates for COVID-19 therapeutics. Previous in vitro and clinical studies suggest that the proprietary Pelargonium sidoides DC. root extract EPs 7630 has antiviral and immunomodulatory properties, limiting symptom severity and disease duration of infections with several upper respiratory viruses. Here we assessed if EPs 7630 affects SARS-CoV-2 propagation and the innate immune response in the human lung cell line Calu-3. In direct comparison to other highly pathogenic CoV (SARS-CoV, MERS-CoV), SARS-CoV-2 growth was most efficiently inhibited at a non-toxic concentration with an IC50 of 1.61 µg/ml. Particularly, the cellular entry step of SARS-CoV-2 was significantly reduced by EPs 7630 pretreatment (10-100 µg/ml) as shown by spike protein-carrying pseudovirus particles and infectious SARS-CoV-2. Using sequential ultrafiltration, EPs 7630 was separated into fractions containing either prodelphinidins of different oligomerization degrees or small molecule constituents like benzopyranones and purine derivatives. Prodelphinidins with a low oligomerization degree and small molecule constituents were most efficient in inhibiting SARS-CoV-2 entry already at 10 µg/ml and had comparable effects on immune gene regulation as EPs 7630. Downregulation of multiple pro-inflammatory genes (CCL5, IL6, IL1B) was accompanied by upregulation of anti-inflammatory TNFAIP3 at 48 h post-infection. At high concentrations (100 µg/ml) moderately oligomerized prodelphinidins reduced SARS-CoV-2 propagation most efficiently and exhibited pronounced immune gene modulation. Assessment of cytokine secretion in EPs 7630-treated and SARS-CoV-2-coinfected Calu-3 cells showed that pro-inflammatory cytokines IL-1ß and IL-6 were elevated whereas multiple other COVID-19-associated cytokines (IL-8, IL-13, TNF-α), chemokines (CXCL9, CXCL10), and growth factors (PDGF, VEGF-A, CD40L) were significantly reduced by EPs 7630. SARS-CoV-2 entry inhibition and the differential immunomodulatory functions of EPs 7630 against SARS-CoV-2 encourage further in vivo studies.

Traditional Herbal Medicines, Bioactive Metabolites, and Plant Products Against COVID-19: Update on Clinical Trials and Mechanism of Actions.

SARS-CoV-2 is the latest worldwide pandemic declared by the World Health Organization and there is no established anti-COVID-19 drug to combat this notorious situation except some recently approved vaccines. By affecting the global public health sector, this viral infection has created a disastrous situation associated with high morbidity and mortality rates along with remarkable cases of hospitalization because of its tendency to be high infective. These challenges forced researchers and leading pharmaceutical companies to find and develop cures for this novel strain of coronavirus. Besides, plants have a proven history of being notable wellsprings of potential drugs, including antiviral, antibacterial, and anticancer therapies. As a continuation of this approach, plant-based preparations and bioactive metabolites along with a notable number of traditional medicines, bioactive phytochemicals, traditional Chinese medicines, nutraceuticals, Ayurvedic preparations, and other plant-based products are being explored as possible therapeutics against COVID-19. Moreover, the unavailability of effective medicines against COVID-19 has driven researchers and members of the pharmaceutical, herbal, and related industries to conduct extensive investigations of plant-based products, especially those that have already shown antiviral properties. Even the recent invention of several vaccines has not eliminated doubts about safety and efficacy. As a consequence, many limited, unregulated clinical trials involving conventional mono- and poly-herbal therapies are being conducted in various areas of the world. Of the many clinical trials to establish such agents as credentialed sources of anti-COVID-19 medications, only a few have reached the landmark of completion. In this review, we have highlighted and focused on plant-based anti-COVID-19 clinical trials found in several scientific and authenticated databases. The aim is to allow researchers and innovators to identify promising and prospective anti-COVID-19 agents in clinical trials (either completed or recruiting) to establish them as novel therapies to address this unwanted pandemic.

Antiviral Activity of Jamaican Medicinal Plants and Isolated Bioactive Compounds.

Plants have had historical significance in medicine since the beginning of civilization. The oldest medical pharmacopeias of the African, Arabian, and Asian countries solely utilize plants and herbs to treat pain, oral diseases, skin diseases, microbial infections, multiple types of cancers, reproductive disorders among a myriad of other ailments. The World Health Organization (WHO) estimates that over 65% of the world population solely utilize botanical preparations as medicine. Due to the abundance of plants, plant-derived medicines are more readily accessible, affordable, convenient, and have safer side-effect profiles than synthetic drugs. Plant-based decoctions have been a significant part of Jamaican traditional folklore medicine. Jamaica is of particular interest because it has approximately 52% of the established medicinal plants that exist on earth. This makes the island particularly welcoming for rigorous scientific research on the medicinal value of plants and the development of phytomedicine thereof. Viral infections caused by the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2), hepatitis virus B and C, influenza A virus, and the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) present a significant global burden. This is a review of some important Jamaican medicinal plants, with particular reference to their antiviral activity.

Plants-Derived Biomolecules as Potent Antiviral Phytomedicines: New Insights on Ethnobotanical Evidences against Coronaviruses.

SARS-CoV-2 infection (COVID-19) is in focus over all known human diseases, because it is destroying the world economy and social life, with increased mortality rate each day. To date, there is no specific medicine or vaccine available against this pandemic disease. However, the presence of medicinal plants and their bioactive molecules with antiviral properties might also be a successful strategy in order to develop therapeutic agents against SARS-CoV-2 infection. Thus, this review will summarize the available literature and other information/data sources related to antiviral medicinal plants, with possible ethnobotanical evidence in correlation with coronaviruses. The identification of novel antiviral compounds is of critical significance, and medicinal plant based natural compounds are a good source for such discoveries. In depth search and analysis revealed several medicinal plants with excellent efficacy against SARS-CoV-1 and MERS-CoV, which are well-known to act on ACE-2 receptor, 3CLpro and other viral protein targets. In this review, we have consolidated the data of several medicinal plants and their natural bioactive metabolites, which have promising antiviral activities against coronaviruses with detailed modes of action/mechanism. It is concluded that this review will be useful for researchers worldwide and highly recommended for the development of naturally safe and effective therapeutic drugs/agents against SARS-CoV-2 infection, which might be used in therapeutic protocols alone or in combination with chemically synthetized drugs.

The Relevance of Complementary and Integrative Medicine in the COVID-19 Pandemic: A Qualitative Review of the Literature.

Background: During the COVID-19 pandemic people are facing risks of adverse health effects due to the restrictions implemented such as quarantine measures, reduced social contact, and self-isolation. In this qualitative review, we collected data on potential preventive and therapeutic health benefits of Complementary and Integrative Medicine (CIM) that might be useful during the COVID-19 pandemic. We have reviewed the scientific literature to summarize CIM practices that could be beneficial for improving physical and mental health and well-being of the population under the current pandemic circumstances. It must be noted that this review is not SARS-CoV-2 specific and we explicitly do not intend to make any SARS-CoV-2 specific health claims in this article. Methods and Findings: A qualitative, non-systematic literature review was conducted in Medline to identify literature describing preventive and therapeutic CIM approaches for strengthening mental and physical health. For a variety of CIM approaches clinical evidence was identified, indicating beneficial effects. CIM approaches include specific dietary measures and selected micronutrients, physical activity, techniques from Mind-Body Medicine, single botanicals or botanical compounds, and spending time in nature among others. The effects of CIM measures on conditions like obesity and hypertension are of special relevance here, as these conditions are considered as risk factors for a severe course of COVID-19. Moreover, a possibly direct effect of CIM approaches on immune functions and clinical parameters in respiratory tract infections, such as influenza, were identified. The findings of this review could be helpful for clinicians, patients, and the general population during the current pandemic when discussing and/or considering CIM options. Conclusions: CIM offers a variety of preventive and therapeutic options for strengthening physical and mental resilience, which could also be useful in the current COVID-19 pandemic. The evidence of CIM approaches with a potential benefit in the COVID-19 pandemic in different areas is worth to be analyzed. While this qualitative review has several obvious limitations, it might serve as useful starting point for further research on this topic.

Potential of Flavonoid-Inspired Phytomedicines against COVID-19.

Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show potential of caflanone to inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1ß, IL-6, IL-8, Mip-1α, TNF-α), and PI4Kiiiß as well as AXL-2, which facilitates mother-to-fetus transmission of coronavirus. The potential for the use of smart drug delivery technologies like nanoparticle drones loaded with these phytomedicines to overcome bioavailability limitations and improve therapeutic efficacy are discussed.

Exploring nature's bounty: identification of Withania somnifera as a promising source of therapeutic agents against COVID-19 by virtual screening and in silico evaluation.

Coronaviruses are etiological agents of extreme human and animal infection resulting in abnormalities primarily in the respiratory tract. Presently, there is no defined COVID-19 intervention and clinical trials of prospective therapeutic agents are still in the nascent stage. Withania somnifera (L.) Dunal (WS), is an important medicinal plant in Ayurveda. The present study aimed to evaluate the antiviral potential of selected WS phytoconstituents against the novel SARS-CoV-2 target proteins and human ACE2 receptor using in silico methods. Most of the phytoconstituents displayed good absorption and transport kinetics and were also found to display no associated mutagenic or adverse effect(s). Molecular docking analyses revealed that most of the WS phytoconstituents exhibited potent binding to human ACE2 receptor, SAR-CoV and SARS-CoV-2 spike glycoproteins as well as the two main SARS-CoV-2 proteases. Most of the phytoconstituents were predicted to undergo Phase-I metabolism prior to excretion. All phytoconstituents had favorable bioactivity scores with respect to various receptor proteins and target enzymes. SAR analysis revealed that the number of oxygen atoms in the withanolide backbone and structural rearrangements were crucial for effective binding. Molecular simulation analyses of SARS-CoV-2 spike protein and papain-like protease with Withanolides A and B, respectively, displayed a stability profile at 300 K and constant RMSDs of protein side chains and Cα atoms throughout the simulation run time. In a nutshell, WS phytoconstituents warrant further investigations in vitro and in vivo to unravel their molecular mechanism(s) and modes of action for their future development as novel antiviral agents against COVID-19.