The Controversial Roles of Areca Nut: Medicine or Toxin?

Areca nut (AN) is used for traditional herbal medicine and social activities in several countries. It was used as early as about A.D. 25-220 as a remedy. Traditionally, AN was applied for several medicinal functions. However, it was also reported to have toxicological effects. In this review article, we updated recent trends of research in addition to acquire new knowledge about AN. First, the history of AN usage from ancient years was described. Then, the chemical components of AN and their biological functions was compared; arecoline is an especially important compound in AN. AN extract has different effects caused by different components. Thus, the dual effects of AN with pharmacological and toxicological effects were summarized. Finally, we described perspectives, trends and challenges of AN. It will provide the insight of removing or modifying the toxic compounds of AN extractions for enhancing their pharmacological activity to treat several diseases in future applications.

Antiviral Activity of Medicinal Plants against Human Coronavirus: a systematic scoping review of and experimentations.

OBJECTIVE: To investigate the and studies of natural compounds and medicinal plants with anti-coronavirus activity. METHODS: A systematic review was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Animal Research: Reporting of experiments guidelines to find data for medicinal plants and natural products effective against human coronaviruses in or studies. Studies published up to September 6, 2020 were included. Studies ( or ) reporting the effect of medicinal plants and natural products or their derivatives on human coronavirus were included RESULTS: Promising anti-coronavirus effects are seen with different herbal compounds like some diterpenoids, sesquiterpenoids, and three compounds in tea with 3CLpro inhibiting effect of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV); Hirsutenone, Six cinnamic amides and bavachinin are PLpro inhibitors and Tanshinones are active on both 3CLpro and PLpro. Some flavonoid compounds of Citrus fruits act on Immun-oregulation and target angiotensin-converting enzyme 2 which is used by SARS-COV for entry. Virus helicase is possibly inhibited by two compounds myricetin and scutellarein. CONCLUSION: This review shows that complementary medicine have the potential for new drug discovery against coronavirus. Further research is needed before definitive conclusions can be made concerning the safety and efficacy of the use of these medicinal plants.

Use of Medicinal Plants in Africa: A Case Study From the Democratic Republic of Congo (DRC).

Although medicinal plants are beneficial, they also can be important risk factors for the development of acute and chronic kidney injury, as well toxicity of other solid organs. There are a lack of reports of adverse kidney events and drug interactions resulting from medicinal plants owing to a lack of professional surveillance and specific data on kidney toxicity, especially in low-resource settings. Within the context of increased medicinal plant use and lack of effective regulatory control, safety is a key priority issue. We review the benefits and adverse effects of medicinal plants with particular reference to nephrotoxicity encountered in the Democratic Republic of Congo in sub-Saharan Africa.

Identification of medicinal plant-based phytochemicals as a potential inhibitor for SARS-CoV-2 main protease (Mpro) using molecular docking and deep learning methods.

Highly transmissive and rapidly evolving Coronavirus disease-2019 (COVID-19), a viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), triggered a global pandemic, which is one of the most researched viruses in the academia. Effective drugs to treat people with COVID-19 have yet to be developed to reduce mortality and transmission. Studies on the SARS-CoV-2 virus identified that its main protease (Mpro) might be a potential therapeutic target for drug development, as this enzyme plays a key role in viral replication. In search of potential inhibitors of Mpro, we developed a phytochemical library consisting of 2431 phytochemicals from 104 Korean medicinal plants that exhibited medicinal and antioxidant properties. The library was screened by molecular docking, followed by revalidation by re-screening with a deep learning method. Recurrent Neural Networks (RNN) computing system was used to develop an inhibitory predictive model using SARS coronavirus Mpro dataset. It was deployed to screen the top 12 compounds based on their docked binding affinity that ranged from -8.0 to -8.9 kcal/mol. The top two lead compounds, Catechin gallate and Quercetin 3-O-malonylglucoside, were selected depending on inhibitory potency against Mpro. Interactions with the target protein active sites, including His41, Met49, Cys145, Met165, and Thr190 were also examined. Molecular dynamics simulation was performed to analyze root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (RG), solvent accessible surface area (SASA), and number of hydrogen bonds. Results confirmed the inflexible nature of the docked complexes. Absorption, distribution, metabolism, excretion, and toxicity (ADMET), as well as bioactivity prediction confirmed the pharmaceutical activities of the lead compound. Findings of this research might help scientists to optimize compatible drugs for the treatment of COVID-19 patients.

Characterization and protein engineering of glycosyltransferases for the biosynthesis of diverse hepatoprotective cycloartane-type saponins in Astragalus membranaceus.

Although plant secondary metabolites are important source of new drugs, obtaining these compounds is challenging due to their high structural diversity and low abundance. The roots of Astragalus membranaceus are a popular herbal medicine worldwide. It contains a series of cycloartane-type saponins (astragalosides) as hepatoprotective and antivirus components. However, astragalosides exhibit complex sugar substitution patterns which hindered their purification and bioactivity investigation. In this work, glycosyltransferases (GT) from A. membranaceus were studied to synthesize structurally diverse astragalosides. Three new GTs, AmGT1/5 and AmGT9, were characterized as 3-O-glycosyltransferase and 25-O-glycosyltransferase of cycloastragenol respectively. AmGT1G146V/I variants were obtained as specific 3-O-xylosyltransferases by sequence alignment, molecular modelling and site-directed mutagenesis. A combinatorial synthesis system was established using AmGT1/5/9, AmGT1G146V/S and the reported AmGT8 and AmGT8A394F . The system allowed the synthesis of 13 astragalosides in Astragalus root with conversion rates from 22.6% to 98.7%, covering most of the sugar-substitution patterns for astragalosides. In addition, AmGT1 exhibited remarkable sugar donor promiscuity to use 10 different donors, and was used to synthesize three novel astragalosides and ginsenosides. Glycosylation remarkably improved the hepatoprotective and SARS-CoV-2 inhibition activities for triterpenoids. This is one of the first attempts to produce a series of herbal constituents via combinatorial synthesis. The results provided new biocatalytic tools for saponin biosynthesis.

Potential medicinal plants to combat viral infections: A way forward to environmental biotechnology.

The viral diseases encouraged scientific community to evaluate the natural antiviral bioactive components rather than protease inhibitors, harmful organic molecules or nucleic acid analogues. For this purpose, medicinal plants have been gaining tremendous importance in the field of attenuating the various kinds of infectious and non-infectious diseases. Most of the commonly used medicines contains the bioactive components/phytoconstituents that are generally extracted from medicinal plants. Moreover, the medicinal plants offer many advantages for the recovery applications of infectious disease especially in viral infections including HIV-1, HIV-2, Enterovirus, Japanese Encephalitis Virus, Hepatitis B virus, Herpes Virus, Respiratory syncytial virus, Chandipura virus and Influenza A/H1N1. Considering the lack of acceptable drug candidates and the growing antimicrobial resistance to existing drug molecules for many emerging viral diseases, medicinal plants may offer best platform to develop sustainable/efficient/economic alternatives against viral infections. In this regard, for exploring and analyzing large volume of scientific data, bibliometric analysis was done using VOS Viewer shedding light on the emerging areas in the field of medicinal plants and their antiviral activity. This review covers most of the plant species that have some novel bioactive compound like gnidicin, gniditrin, rutin, apigenin, quercetin, kaempferol, curcumin, tannin and oleuropin which showed high efficacy to inhibit the several disease causing virus and their mechanism of action in HIV, Covid-19, HBV and RSV were discussed. Moreover, it also delves the in-depth mechanism of medicinal with challenges and future prospective. Therefore, this work delves the key role of environment in the biological field.

In Silico Identification of Anti-SARS-CoV-2 Medicinal Plants Using Cheminformatics and Machine Learning.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of COVID-19, is spreading rapidly and has caused hundreds of millions of infections and millions of deaths worldwide. Due to the lack of specific vaccines and effective treatments for COVID-19, there is an urgent need to identify effective drugs. Traditional Chinese medicine (TCM) is a valuable resource for identifying novel anti-SARS-CoV-2 drugs based on the important contribution of TCM and its potential benefits in COVID-19 treatment. Herein, we aimed to discover novel anti-SARS-CoV-2 compounds and medicinal plants from TCM by establishing a prediction method of anti-SARS-CoV-2 activity using machine learning methods. We first constructed a benchmark dataset from anti-SARS-CoV-2 bioactivity data collected from the ChEMBL database. Then, we established random forest (RF) and support vector machine (SVM) models that both achieved satisfactory predictive performance with AUC values of 0.90. By using this method, a total of 1011 active anti-SARS-CoV-2 compounds were predicted from the TCMSP database. Among these compounds, six compounds with highly potent activity were confirmed in the anti-SARS-CoV-2 experiments. The molecular fingerprint similarity analysis revealed that only 24 of the 1011 compounds have high similarity to the FDA-approved antiviral drugs, indicating that most of the compounds were structurally novel. Based on the predicted anti-SARS-CoV-2 compounds, we identified 74 anti-SARS-CoV-2 medicinal plants through enrichment analysis. The 74 plants are widely distributed in 68 genera and 43 families, 14 of which belong to antipyretic detoxicate plants. In summary, this study provided several medicinal plants with potential anti-SARS-CoV-2 activity, which offer an attractive starting point and a broader scope to mine for potentially novel anti-SARS-CoV-2 drugs.

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.

Comparison study of Beninese and Chinese herbal medicines in treating COVID-19.

ETHNOPHARMACOLOGICAL RELEVANCE: The worldwide use of natural remedies is an alternative therapeutic solution to strengthen immunity, fight, and prevent this disease. The rapid spread of the coronavirus disease worldwide has promoted the search for therapeutic solutions following different approaches. China and Benin have seen the use of natural remedies such as Chinese herbal medicine and local endemic plants as alternative solutions in treating COVID-19. AIM OF THE STUDY: The present study was designed to identify the prevalence of medicinal plant use in four municipalities of Benin most affected by COVID-19 and compare them with traditional Chinese medicine and finally verify the efficacy of the main components of the six plants most frequently used, via in vitro experiments. MATERIALS AND METHODS: This study targeting market herbalists and traditional healers was conducted in the form of an ethnomedicinal survey in four representative communities (Cotonou, Abomey-Calavi, Zè, and Ouidah) of southern Benin. The chemical compositions of the six most commonly used herbs were investigated using network pharmacology. Network-based global prediction of disease genes and drug, target, function, and pathway enrichment analysis of the top six herbs was conducted using databases including IPA and visualised using Cytoscape software. The natural botanical drugs involved three medicines and three formulas used in the treatment of COVID-19 in China from the published literature were compared with the top six botanical drugs used in Benin to identify similarities between them and guide the clinical medication in both countries. Finally, the efficacy of the common ingredients in six plants was verified by measuring the viability of BEAS-2B cells and the release of inflammatory factors after administration of different ingredients. Binding abilities of six components to COVID-19 related targets were verified by molecular docking. RESULTS: According to the medication survey investigation, the six most used herbs were Citrus aurantiifolia (13.18%), Momordica charantia (7.75%), Ocimum gratissimum (7.36%), Crateva adansonii (6.59%), Azadirachta indica (5.81%), and Zanthoxylum zanthoxyloides (5.42%). The most represented botanical families were Rutaceae, Lamiaceae, Cucurbitaceae, Meliaceae, and Capparaceae. The network pharmacology of these six herbal plants showed that the flavonoids quercetin, kaempferol, and ß-sitosterol were the main active ingredients of the Benin herbal medicine. Chinese and Beninese herbal medicine are similar in that they have the same targets and pathways in inflammation and oxidative stress relief. Mild COVID-19-related targets come from C. aurantiifolia and M. charantia, and severe COVID-19-related targets come from A. indica A. Juss. Cell viability and enzyme-linked immunosorbent assay results confirmed that six major compounds could protect BEAS-2B cells against injury by inhibiting the expression of inflammatory factors, among which quercetin and isoimperatorin were more effective. Docking verified that the six compounds have good binding potential with COVID-19 related targets. CONCLUSIONS: These results suggest that Benin herbal medicine and Chinese herbal medicine overlap in compounds, targets, and pathways to a certain extent. Among the commonly used plants in Benin, C. aurantiifolia and M. charantia may have a good curative effect on the treatment of mild COVID-19, while for severe COVID-19, A. indica can be added on this basis.

An efficient method for qualitation and quantitation of multi-components of the herbal medicine Qingjin Yiqi Granules.

Qingjin Yiqi Granules (QJYQ) is a Traditional Chinese Medicines (TCMs) prescription for the patients with post-COVID-19 condition. It is essential to carry out the quality evaluation of QJYQ. A comprehensive investigation was conducted by establishing deep-learning assisted mass defect filter (deep-learning MDF) mode for qualitative analysis, ultra-high performance liquid chromatography and scheduled multiple reaction monitoring method (UHPLC-sMRM) for precise quantitation to evaluate the quality of QJYQ. Firstly, a deep-learning MDF was used to classify and characterize the whole phytochemical components of QJYQ based on the mass spectrum (MS) data of ultra-high performance liquid chromatography quadrupole time of flight tandem mass spectrometry (UHPLC-Q-TOF/MS). Secondly, the highly sensitive UHPLC-sMRM data-acquisition method was established to quantify the multi-ingredients of QJYQ. Totally, nine major types of phytochemical compounds in QJYQ were intelligently classified and 163 phytochemicals were initially identified. Furthermore, fifty components were rapidly quantified. The comprehensive evaluation strategy established in this study would provide an effective tool for accurately evaluating the quality of QJYQ as a whole.

'A disease like any other' traditional, complementary and alternative medicine use and perspectives in the context of COVID-19 among the Congolese community in Belgium.

BACKGROUND: As a hard-hit area during the COVID-19 pandemic, Belgium knew the highest mortality among people from sub-Saharan African descent, compared to any other group living in the country. After migration, people often maintain traditional perceptions and habits regarding health and healthcare, resulting in a high prevalence of traditional, complementary and alternative medicine use among different migrant communities in northern urban settings. Despite being the largest community of sub-Saharan African descent in Belgium, little is known on ethnobotanical practices of the Belgian Congolese community. We therefore conducted an exploratory study on the use of medicinal plants in the context of COVID-19 and perceptions on this new disease among members of the Congolese community in Belgium. METHODS: We conducted 16 in-depth semi-structured interviews with people of Congolese descent currently living in Belgium. Participants were selected using purposive sampling. Medicinal plant use in the context of COVID-19 was recorded through free-listing. Data on narratives, ideas and perceptions on the origin, cause/aetiology and overall measures against COVID-19 (including vaccination) were collected. Interview transcripts were analysed using thematic analysis. RESULTS: Four overarching themes emerged from our data. Firstly, participants perceived the representation of the severity of COVID-19 by the Belgian media and government-and by extend by all governmental agencies in the global north-as exaggerated. As a result, traditional and complementary treatments were seen as feasible options to treat symptoms of the disease. Fifteen forms of traditional, complementary and alternative medicine were documented, of which thirteen were plants. Participants seem to fold back on their Congolese identity and traditional knowledge in seeking coping strategies to deal with the COVID-19 pandemic. Finally, institutional postcolonial distrust did not only seem to lead to distrust in official messages on the COVID-19 pandemic but also to feelings of vaccination hesitancy. CONCLUSION: In the context of the COVID-19 pandemic, participants in our study retreated to, reshaped and adapted traditional and culture-bound knowledge. This study suggests that the fragile and sensitive relationship between sub-Saharan African migrant groups and other social/ethnic groups in Belgium might play a role in their sensitivity to health-threatening situations, such as the COVID-19 pandemic.

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.

In Vitro and In Silico Studies for the Identification of Potent Metabolites of Some High-Altitude Medicinal Plants from Nepal Inhibiting SARS-CoV-2 Spike Protein.

Despite ongoing vaccination programs against COVID-19 around the world, cases of infection are still rising with new variants. This infers that an effective antiviral drug against COVID-19 is crucial along with vaccinations to decrease cases. A potential target of such antivirals could be the membrane components of the causative pathogen, SARS-CoV-2, for instance spike (S) protein. In our research, we have deployed in vitro screening of crude extracts of seven ethnomedicinal plants against the spike receptor-binding domain (S1-RBD) of SARS-CoV-2 using an enzyme-linked immunosorbent assay (ELISA). Following encouraging in vitro results for Tinospora cordifolia, in silico studies were conducted for the 14 reported antiviral secondary metabolites isolated from T. cordifolia-a species widely cultivated and used as an antiviral drug in the Himalayan country of Nepal-using Genetic Optimization for Ligand Docking (GOLD), Molecular Operating Environment (MOE), and BIOVIA Discovery Studio. The molecular docking and binding energy study revealed that cordifolioside-A had a higher binding affinity and was the most effective in binding to the competitive site of the spike protein. Molecular dynamics (MD) simulation studies using GROMACS 5.4.1 further assayed the interaction between the potent compound and binding sites of the spike protein. It revealed that cordifolioside-A demonstrated better binding affinity and stability, and resulted in a conformational change in S1-RBD, hence hindering the activities of the protein. In addition, ADMET analysis of the secondary metabolites from T. cordifolia revealed promising pharmacokinetic properties. Our study thus recommends that certain secondary metabolites of T. cordifolia are possible medicinal candidates against SARS-CoV-2.

Assessing knowledge of herbal medicine course for dental students.

BACKGROUND: The aims of this article are to assess dental students' knowledge about herbal medicine usage and the potential benefits and side effects, and to conduct a short course about herbal medicine. METHODS: All fourth-year pre-doctoral students were invited to participate in a herbal medicine course as a test while the sixth-year students were the control group. A survey was tested for validity and reliability. It comprised of 16 multiple choice questions was given before the course and one month after the course. The sum score of knowledge for each participant was calcuated based on the ability to identify the use of herbs in dentistry with high-quality evidence (correct answer) or total answer for periodontal disease and caries. RESULTS: The response rate for completing the study was 112 fourth-year students (73.7%) and 64 sixth-year students (39.0%). More than half of the participants (52.5%) were unsure about the importance of herbal medicine in dentistry. However, the majority also stated that the most common herbs used in dentistry were clove (62.9%), followed by curcuma turmeric (54.7%) and meswak (43.0%). The fourth-year students displayed evidence of a higher overall knowledge score after the course in herbal medicine related to periodontal disease in total and correct answers (mean 4.48 ± 4.13, 3.73 ± 3.31, respectively) compared to before the course (mean 0.84 ± 1.23, 0.74 ± 1.16, respectively) (p-value < 0.001). The post-course periodontal disease total and correct answers were statistically significant between fourth- and sixth-year students. CONCLUSION: Herbal medicine has a potential positive impact on dentistry. However, these effects are not fully investigated and received full attention in academic institute. This short educational program related to medicinal herbs can improve the knowledge of dental students. This will help increase the awareness about the use and potential side effects of herbal medicine in the dental field.

Essential Oils and COVID-19.

Herbal products are a major source of herbal medicines and other medicines. Essential oils have shown various pharmacological activities, such as antiviral activity, and therefore are proposed to have potential activity against SARS-CoV-2. Due to their lipophilicity, essential oils can easily penetrate the viral membrane and cause the viral membrane to rupture. In addition, crude essential oils usually have many active constituents that can act on different parts of the virus including its cell entry, translation, transcription, and assembly. They have further beneficial pharmacological effects on the host's respiratory system, including anti-inflammatory, immune regulation, bronchiectasis, and mucolytics. This review reported potential essential oils which could be promising drugs for COVID-19 eradication. Essential oils have many advantages because they are promising volatile antiviral molecules, making them potential drug targets for the prevention and treatment of COVID-19, whether used alone or in combination with other chemotherapeutic drugs. The aim of the current review is to shed light on the potential essential oils against enveloped viruses and their proposed activity against SARS-CoV-2 which is also an enveloped virus. The objectives were to present all data reflecting the promising activities of diverse essential oils against enveloped viruses and how they could contribute to the eradication of COVID disease, especially in indoor places. The data collected for the current review were obtained through the SciFinder database, Google scholar, PubMed, and Mendeley database. The data of the current review focused on the most common essential oils which are available in the pharmaceutical market and showed noticeable activities against enveloped viruses such as HSV and influenza.

Potential medicinal plants involved in inhibiting 3CLpro activity: A practical alternate approach to combating COVID-19.

At present, a variety of vaccines have been approved, and existing antiviral drugs are being tested to find an effective treatment for coronavirus disease 2019 (COVID-19). However, no standardized treatment has yet been approved by the World Health Organization. The virally encoded chymotrypsin-like protease (3CLpro) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which facilitates the replication of SARS-CoV in the host cells, is one potential pharmacological target for the development of anti-SARS drugs. Online search engines, such as Web of Science, Google Scholar, Scopus and PubMed, were used to retrieve data on the traditional uses of medicinal plants and their inhibitory effects against the SARS-CoV 3CLpro. Various pure compounds, including polyphenols, terpenoids, chalcones, alkaloids, biflavonoids, flavanones, anthraquinones and glycosides, have shown potent inhibition of SARS-CoV-2 3CLpro activity with 50% inhibitory concentration (IC50) values ranging from 2-44 µg/mL. Interestingly, most of these active compounds, including xanthoangelol E (isolated from Angelica keiskei), dieckol 1 (isolated from Ecklonia cava), amentoflavone (isolated from Torreya nucifera), celastrol, pristimerin, tingenone and iguesterin (isolated from Tripterygium regelii), tannic acid (isolated from Camellia sinensis), and theaflavin-3,3'-digallate, 3-isotheaflav1in-3 gallate and dihydrotanshinone I (isolated from Salvia miltiorrhiza), had IC50 values of less than 15 µg/mL. Kinetic mechanistic studies of several active compounds revealed that their mode of inhibition was dose-dependent and competitive, with Ki values ranging from 2.4-43.8 µmol/L. Given the significance of plant-based compounds and the many promising results obtained, there is still need to explore the phytochemical and mechanistic potentials of plants and their products. These medicinal plants could serve as an effective inexpensive nutraceutical for the general public to help manage COVID-19.

Antiviral Potential of Plants against COVID-19 during Outbreaks-An Update.

Several human diseases are caused by viruses, including cancer, Type I diabetes, Alzheimer's disease, and hepatocellular carcinoma. In the past, people have suffered greatly from viral diseases such as polio, mumps, measles, dengue fever, SARS, MERS, AIDS, chikungunya fever, encephalitis, and influenza. Recently, COVID-19 has become a pandemic in most parts of the world. Although vaccines are available to fight the infection, their safety and clinical trial data are still questionable. Social distancing, isolation, the use of sanitizer, and personal productive strategies have been implemented to prevent the spread of the virus. Moreover, the search for a potential therapeutic molecule is ongoing. Based on experiences with outbreaks of SARS and MERS, many research studies reveal the potential of medicinal herbs/plants or chemical compounds extracted from them to counteract the effects of these viral diseases. COVID-19's current status includes a decrease in infection rates as a result of large-scale vaccination program implementation by several countries. But it is still very close and needs to boost people's natural immunity in a cost-effective way through phytomedicines because many underdeveloped countries do not have their own vaccination facilities. In this article, phytomedicines as plant parts or plant-derived metabolites that can affect the entry of a virus or its infectiousness inside hosts are described. Finally, it is concluded that the therapeutic potential of medicinal plants must be analyzed and evaluated entirely in the control of COVID-19 in cases of uncontrollable SARS infection.

Natural products from medicinal plants in Asia and the Pacific for RNA viruses: Hercules' fifth labour.

CONTEXT: The emergence of zoonotic viruses in the last decades culminating with COVID-19 and challenges posed by the resistance of RNA viruses to antiviral drugs requires the development of new antiviral drugs. OBJECTIVE: This review identifies natural products isolated from Asian and Pacific medicinal plants with in vitro and in vivo antiviral activity towards RNA viruses and analyses their distribution, molecular weights, solubility and modes of action. MATERIALS AND METHODS: All data in this review was compiled from Google Scholar, PubMed, Science Direct, Web of Science, ChemSpider, PubChem and library search from 1961 to 2022. RESULTS: Out of about 350 molecules identified, 43 phenolics, 31 alkaloids, and 28 terpenes were very strongly active against at least one type of RNA virus. These natural products are mainly planar and amphiphilic, with a molecular mass between 200 and 400 g/mol and target viral genome replication. Hydroxytyrosol, silvestrol, lycorine, tylophorine and 12-O-tetradecanoylphorbol 13-acetate with IC50 below 0.01 µg/mL and selectivity index (S.I.) above 100 have the potential to be used for the development of anti-RNA virus leads. DISCUSSION AND CONCLUSIONS: The medicinal plants of Asia and the Pacific are a rich source of natural products with the potential to be developed as lead for the treatment of RNA viral infections.

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.

New Frontier in Antiviral Drugs for Disorders of the Respiratory System.

BACKGROUND: COVID-19 is still soaring, and the new delta COVID-19 variant is on the rise and spreading around the world. OBJECTIVE: We conducted a patent analysis to better understand the therapeutic strategy developed for antivirals available for the disorders of the respiratory system. MATERIALS AND METHODS: European granted patents filed from January 2002 to June 2021 were analyzed. We used a combination of International patent classification (IPC) "A61p31/12" and "A61p11/00" to search the relevant documents. RESULTS: Our study showed R&D of antiviral drugs for disorders of the respiratory system to be decreasing over the past 20 years. Chemical drugs showed various chemical structures. The development of chemical drugs or herbal medicines appeared to commence earlier than the biological products. Also, the results indicated that large global companies play a leading role in developing kinase inhibitors as chemical drugs. CONCLUSION: There are three strategies for developing antiviral drugs for the disorders of the respiratory system, including chemical drugs, herbal medicines or natural products, and biological products. Herbal medicines may provide a new insight and approach to developing antiviral drugs for disorders of the respiratory system. A combination of chemical drugs and natural products may be a promising therapeutic method for treating patients with COVID- 19.