Supplement Gone Wrong: Drug-Induced Liver Injury Caused by Artemisinin

Introduction: Drug-induced liver injury (DILI) is defined as hepatic dysfunction caused by prescription medications, supplements, or xenobiotics after alternative causes have been excluded. As one of the leading causes of acute liver failure, DILI should be considered when patients present with hepatic dysfunction. We present a case of symptomatic DILI secondary to artemisinin use. Case Description/Methods: A 78-year-old Chinese man with no medical history presented to the hepatology clinic with 10 weeks of jaundice, weakness, and pruritis. He started taking Artemisinin/ Bioperine 12 weeks ago to prevent COVID-19 but stopped 3 weeks ago. He denied abdominal pain, a family history of liver disease, substance/alcohol use, and taking other concomitant drugs. Physical examination revealed scleral icterus and no other signs of chronic liver disease. Laboratory studies showed total bilirubin 11 mg/dL, alkaline phosphatase 293 U/L, aspartate transaminase 170 U/L, and alanine transaminase 196 U/L with negative workup for hepatitis A, B, and C. CT abdomen and MRCP were unremarkable for liver or biliary pathology. Further serological workup was negative and follow-up labs revealed normalization of liver enzymes and bilirubin. Given the patient's improvement, liver biopsy was not pursued. The patient was instructed to avoid supplements unless prescribed by a physician. Discussion(s): DILI is a global issue with an estimated annual incidence rate of 13.9 to 24.0 per 100,000 persons. Diagnosing DILI is important as it can cause acute liver injury and liver failure in certain cases. Since COVID-19 emerged, supplement use has increased given claims of boosting the immune system. Artemisinin is an herb used in traditional Chinese medicine with antimalarial activity investigated to be a possible COVID-19 treatment, but no current evidence exists to support it being effective against COVID-193. Our patient's supplement also contained Bioperine, a black pepper extract, which is likely benign. Contrarily, artemisinin is a well-described cause of idiosyncratic acute liver injury and hepatotoxicity, causing self-limited mild to moderate transaminitis but also severe cases requiring emergent livertransplantation. Our patient's unrevealing workup, his spontaneous improvement correlating with supplement discontinuation, and RUCAM score of 7 led to high suspicion of DILI secondary to artemisinin. Providers should always ask patients about supplement use and consider DILI when patients present with liver injury. (Table Presented).

In-silico screening of plant-derived natural compounds for their anti-COVID-19 potential

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, in December 2019 and quickly spread across the worldwide. It becomes a global pandemic and risk to the healthcare system of almost every nation around the world. In this study thirty natural compounds of 19 Indian herbal plants were used to analyze their binding with eight proteins associated with COVID -19. Based on the molecular docking as well as ADMET analysis, isovitexin, glycyrrhizin, sitosterol, and piperine were identified as potential herbal medicine candidates. On comparing the binding affinity with Ivermectin, we have found that the inhibition potentials of the Trigonella foenum-graecum (fenugreek), Glycyrrhiza glabra (licorice), Tinospora cordifolia (giloy) and Piper nigrum (black pepper) are very promising with no side-effects.

Growth acceleration/deceleration in Indian spices economy

The consumption of spices is growing in India with an increase in purchasing power. It is forecasted that everyone in the country would be consuming one spice or the other with a high per capita consumption. It is estimated that we may have a population of around 1.69 billion people during 2050 and approximately the per capita consumption of turmeric, ginger, black pepper and cardamom is expected to be about 1.6 kg, 1.2 kg, 148 g and 54 g, respectively. This may increase further owing to rapid urbanization which needs spices as natural food preservatives. Hence, the present study was conducted to analyze the growth trend in spices economy of India during the period 1990-91 to 2021-22 with reference to the selected growth indicators such as area, production, domestic market, export and export value. For estimating the acceleration in the growth rates, the paper uses semi-logarithmic specification of a non-linear (quadratic) equation. From the analysis, it is observed that there is a huge scope for output and export of spices. Despite the Covid pandemic, spices export from India has continued its upward trend during 2020-21 and has attained an all-time high of US $ 4.0 billion mark for the first time in the history of spices export. It also implies that there is strong domestic market for spices in India.

Home Remedies, Dietary and Lifestyle Changes during Covid-19 Pandemic

December 2019 has become one of the most surprising days in the whole world in light of the flare-up of a most infectious sickness brought about by novel Covid or Severe Acute Respiratory Syndrome Corona virus 2 (SARS-CoV-2). This study is conducted to assess the benefits of the use of home remedies to prevent the cause of Covid-19 and evaluate the assessment of dietary changes and physical activity in the prevention of Covid-19. A questionnaire-based online survey is conducted using Google forms consisting of multiple-choice questions about home remedies, lifestyle and dietary changes made by the people during this pandemic. These home remedies included using different types of herbal preparations, steam inhalation, physical exercise and OTC medications for prophylaxis. Questions likewise included about being infected by Coronavirus-19(during first wave or second) and their recovery period, additionally collected their viewpoint for changes made, for example how much they are useful in the prevention of the attack and whenever encountered any undesirable impacts. Total responses were 210, among which 121(57.6%) responses were from females and 89(42.4%) from males. 65 people tested Covid positive (42 during the first wave and 23 during the second wave). 118(56.2%) of people think these changes are very beneficial. (Rated 4 and 5 out of 5 points). From our survey, we concluded that different herbal preparations of their composition, which they thought are helpful, and steam inhalations have been used. Rating regarding the use and effectiveness was also found to be average. Further studies are needed to prove and provide clear evidence about adverse and side effects associated with the use of herbal products.Copyright © 2022 Society of Pharmaceutical Sciences and Research. All rights reserved.

Indian medicinal plants are effective in the treatment and management of COVID-19

Indian medicinal plants are referred to as the "nectar of life" owing to their phytochemicals and bioactive complexes that are beneficial in treating diseases. Coronavirus disease 2019 (COVID-19) is a global health issue without any proper medication. The indigenous plants of India can be exploited to control the precise signs of SARS-CoV-2. The Ministry of AYUSH (Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homeopathy) has advised routine usage of medicinal plants for COVID-19. Medicinal plants like Zingiber officinalis, Azadirachta indica, Ocimum sanctum, Nigella sativa, Withania somnifera, Curcuma longa, Piper nigrum, Allium sativum, Tinospora cordifolia, etc. have immunity-boosting, antiviral, antibacterial, antioxidant and anti-inflammatory actions that can suppress and treat symptoms of COVID-19. In vitro, in vivo as well as in silico validation, these phytochemicals can help us to manage and treat COVID-19 disease. This integration of traditional knowledge in the prophylaxis of corona infection and current skills validating it for the development of precise and powerful therapeutic approaches will more efficiently resolve different clinical aspects of COVID-19. The review focuses on both traditional and emergent methods to prevent and treat COVID-19 with various Indian medicinal plants along with their phytochemicals.Copyright © 2023 Authors. All rights reserved.

Role of spices in Phytomedicine - An overview

Phytomedicines are plant derived substances used for medicinal purposes with great potential and abundance. Spices have a traditional history of use as natural products that have been extensively used worldwide in healthrelated problems as well as medicinal purposes such as in enhancing immunity and providing numerous health benefits. The major spices such as small cardamom (Elettaria cardamomum Maton), pepper (Piper nigrum L.), ginger (Zingiber officinale Rosc), turmeric (Curcuma longa L), cumin (Cuminum cyminum L), mustard (Brassica nigra L) and fenugreek (Trigonella foenum-graecum) are playing important roles in phytomedicine to cure various human diseases. The active ingredients of spices which includes cardamom (1,8-cineole, alpha-terpinyl acetate, sabinene and beta-linalool), pepper (piperine), ginger (Gingerol, shogaol and zerumbone), turmeric(curcumin) and cumin (cumin aldehyde, eugenol, pinene, phenolic acids). Cardamom is coined as Queen of spices and is used for medicinal purposes both in modern and indigenous systems. Cardamom essential oil has antioxidant, antiseptic, carminative, digestive, diuretic, stimulant, stomachic, tonic, antispasmodic, anti-diabetic, antimicrobial, antiinflammatory, anti-cancer, gastroprotective and insecticidal properties. It is also used as an aphrodisiac. It is helpful in reducing the irritation endured during premenstrual strain. It works well against respiratory trouble thus helping to ease coughs and to warm up the body. The seeds of cardamom are considered to be stimulant, carminative, stomachic, diuretic, cardiotonic and abortifacient. They are useful in treating bronchitis, haemorrhoids, strangury, renal and vesical calculi, anorexia, dyspepsia and gastropathy. They are chewed to prevent bad breath and pyrosis i.e. excessive watering in the mouth. Adding powdered cardamom seeds can impart a very pleasant aroma to the tea, which is also used as medicine for scanty urination, diarrhoea, palpitation of the heart, exhaustion due to overwork and depression among other things. Pepper is often referred to as King of spices' 'and has anticancer, antimicrobial, anti- inflammatory and antiglycan properties. The antioxidant activity of black pepper comes from alkaloid-derived piperine which inhibits free radicals and reactive oxygen species, reduces lipid peroxidation and positively affects antioxidant molecules, antioxidant enzymes and cellular thiol status. Ginger is a rhizomatic spice crop containing various phenolic substances and antioxidant compounds in addition to the antioxidant properties, these compounds have antiglycan activity and other potential antidiabetic effects. In addition to this, Gingerol, shogaol and zerumbone are bioactive compounds of ginger. Gingerol is the most effective compound that has an antidiabetic activity and increases glucose uptake. Ginger is widely used for dyspepsia, flatulence, abdominal discomfort, nausea and as astringent (an agent that causes shrinkage of mucous membranes or exposed tissues and that is often used internally to check discharge of blood serum or mucous secretions) used as an alternative medicine for the inflammation treatment, low back pain and also used to treat acute tonsillitis. Turmeric is also preferred as an anti-inflammatory agent in traditional medicine for the treatment of skin disorders, wounds, digestive and liver problems. Turmeric is especially valuable for curcumin, which is one of the main components of turmeric. Curcumin together with other related pigments, gives the plant a yellow color. Chemically, these pigments are polyphenols, which are called curcuminoids. Curcumin is shown to have potential antihyperglycemic, antioxidant and immunomodulatory effects. As a traditional remedy, turmeric has also been quite extensively used for centuries to treat various disorders such as rheumatism, body ache, skin diseases, intestinal worms, diarrhoea, intermittent fevers, hepatic diseases, urinary discharges, dyspepsia, inflammations, constipation, leukoderma, amenorrhea, dental diseases, digestive problem such as dy pepsia and acidity, indigestion, flatulence, ulcers and colic inflammatory disorders such as arthritis, colitis and hepatitis. The spice crop, mustard has various bio active compounds containing carotenes, phenolic substances such as quercetin and kaempferol. Among these compounds glucosinolates have been recognized as potential anticancer agents. Cumin contains cumin aldehyde, eugenol, pinene and some other small compounds in cumin oil are active antimicrobial agents against pathogens. In addition, cumin seeds are rich in phenols and flavonoids and contain a wide spectrum of phenolic acids such as galial, cinnamic, rosmarinic, cumaric and vanillic acids. Cumin seeds are used for the treatment of dyspepsia and diarrhoea especially because of the active compound called cuminaldehyde. It is also believed that it is also used for the treatment of diabetes. Fenugreek is used as an aphrodisiac, astringent, demulcent action, carminative, stomachic, diuretic, emmenagogue, emollient, expectorant, restorative and tonic. Fenugreek also used for a variety of health situations including digestive disorders, bronchitis, tuberculosis infection, fevers, sore throat, arthritis, abscesses, swollen glands, skin irritations reaction, loss of appetite, ulcers and menopausal symptoms, diabetes as well as in the treatment of cancerous infection. Leaves infusion is used as a gargle for treatment of mouth ulcers. It also overcomes problem related to reduce blood sugar level and to lower blood pressure. In the recent Covid-19 pandemic, the mixed extracts of spices such as pepper, cardamom, clove, turmeric and ginger were found effective in reducing the Covid-19 pandemic due to the antiviral properties of these spices.

LIVER INJURY ASSOCIATED WITH TURMERIC&≤x2013;A GROWING PROBLEM: NINE CASES FROM THE DRUG-INDUCED LIVER INJURY NETWORK [DILIN]

BACKGROUND: Turmeric (curcumin) is a commonly used over-the-counter herbal product whose uses include diarrhea, arthritis, cancer and even COVID-19. Recently turmeric has been implicated in cases of clinically apparent liver injury with jaundice. The aim of this case series is to describe the clinical, histologic and human leukocyte antigen (HLA) associations of turmeric-associated hepatotoxicity as seen in the U.S. Drug Induced Liver Injury Network (DILIN) Prospective Study. METHODS: All adjudicated cases enrolled in DILIN between 2003-2020 with turmeric as an implicated product were reviewed. Causality was assessed using a 5-point expert opinion score. Available products were collected and analyzed for the presence of turmeric using ultra-high-performance liquid chromatography. Genetic analyses included HLA sequencing. RESULTS: Of 1697 cases of drug-induced liver injury judged to be definite, highly likely or probable (high confidence), nine (0.5%) were attributed to turmeric, all of which were enrolled since 2012, and 6 since 2017 (Figure). The 9 cases included 7 women, 8 whites, with a mean age of 51 years (range, 35-62 years) and BMI 25 kg/m2 (range, 15-40). Seven patients used alcohol, but none to excess, and none had underlying liver disease. Turmeric was used for an average of 102 days before onset of injury (range, 30-425 days). Initial mean ALT was 1179 U/L (range, 328-2245), ALP 211 U/L (41-441), total bilirubin 5.9 mg/dL (1.2-10.8), and INR 1.0 (0.9-1.2). Six patients developed jaundice, and serum bilirubin peaked at 9.6 mg/dL (0.8-26), and INR 2.3 (1.0- 9.7). Liver injury was hepatocellular in 8 patients (mean R = 22). Five patients had elevated antinuclear antibody (ANA) titer and two anti-smooth muscle (ASM) antibody, but none were treated with corticosteroids. Liver biopsy in 5 patients showed portal and lobular mixed inflammatory infiltrates with lymphocytes and eosinophils typical of drug-induced liver injury. Five patients were hospitalized, and one patient died of acute liver failure. Chemical analysis confirmed the presence of turmeric in all 7 products analyzed;3 also contained piperine (black pepper), and none contained green tea. Of 7 patients with HLA typing available, 4 carried HLA-B*35:01, a class I HLA allele previously implicated in both green tea and Polygonum multiflorum hepatotoxicity. CONCLUSION: Liver injury due to turmeric appears to be increasing, perhaps, reflecting usage patterns or increased combination with black pepper, which increases its absorption. Turmeric liver injury, similar to that caused by other polyphenolic herbal products, is typically hepatocellular, with a latency of 1 to 6 months, and is linked to HLA-B*35:01. While most cases are self-limited, the injury can be severe and result in death or liver transplantation.

Monitoring of Black Pepper Growth at Different Elevation using Ground Data and NDVI Time Series

Implementation of remote sensing in agriculture helps to enhance crop growth monitoring especially during the Covid-19 pandemic. To enhance black pepper growth condition, a study was conducted at two study sites in Bintulu, Sarawak. Hence, this study aims (i) to construct a black pepper growth monitoring at different levels of elevation in Suka Farm (SF) and Taime Farm (TF);and (ii) to integrate limited ground data and NDVI time series from Landsat 8OLI for black pepper growth monitoring. Elevation maps were generated using Natural Neighbor (NN) based on the ground data analysed using ArcGIS 10.4 Software. Three elevation levels were classified into the lower, middle, and upper levels. Observational ground data and NDVI time series of Landsat 8 OLI were calculated using SAS 9.4 software. All parameters then correlating with the elevation levels using Pearson Correlation Coefficient. Optimum growth of black pepper growth in SF and TF was identified at an elevation range between 39m–50m. The NDVI time series also indicated equivalent results as the ground data. This study proposed that the elevation of an area gives a significant impact on black pepper growth. Besides, the NDVI time series of Landsat 8 OLI was feasible for monitoring black pepper growth.

Ayurveda and Siddha systems polyherbal formulations to treat COVID-19 caused by SARS-CoV-2 and brief insight on application of Molecular Docking and SWISS Target prediction tools to study efficacy of active molecules

Ayurveda and Siddha systems are the two ancient medical systems originated in India more than 4000 years ago had given many formulary and treatment methods against influenza like infections. Kabasura churan from Siddha system and Maha sudharshan churan from the Ayurvedic system are the two major formulations along with many other individual herbs mentioned in the texts to treat Influenza like infections. Kabasura churan and Maha Sudarshan churan both have antipyretic, analgesic and anti-inflammatory effects. Both formulations were prepared according to Siddha and Ayurvedic texts. Herbs mentioned in both formulations like Turmeric, Tulsi (Basil), Kalmegh (Andrographis), Black Pepper, Liquorice (Mulethi), and Dronapushpi (Leucas) etc., had direct antiviral effect. Herbs like Aswagandha, Ginger, Guduchi (Tinospora), Kulanjan (Galangal) etc., had immunomodulatory and anti-inflammatory effect. Active compounds from different herbs were selected to study their antiviral activity through molecular docking algorithm. Application of modern of tools like Bioinformatics and Highthroughput screening methods can predict the efficacy of the ancient documented formulations and can be compared as per their literature. Compounds like curcumin, Glycyrrhizin, Ursolic acid, Quercetin, Andrographolide, Coumarins etc. were showed polyspecific activity like inhibition of Spike protein, Furin, Main Protease (Mpro) and Papain like Proteases (PLpro). Thus we propose use of Kabasura churan and Maha Sudharshan churan as alternative complementary medicine as a palliative treatment against COVID-19 caused by SARS-CoV-2 by conducting proper Randomized Clinical Trials.

Philippine medicinal plants with potentialimmunomodulatory and anti-SARS-CoV-2 activities

Coronavirus disease 2019 (COVID-19) continues to devastate the world's health and economy, affecting all aspects of life leading to widespread social disruption. Even as several vaccines have been developed, their availability in developing countries is limited and their efficacy against the variants of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) needs to be continuously assessed. The World Health Organization (WHO) has acknowledged that vaccines alone will not overcome the global challenges of COVID-19. Medicinal plants may provide the needed support. Herein, we identify Philippine medicinal plants that possess phytochemicals with potential anti-SARS-CoV-2 activity and/or immunomodulatory properties that may strengthen one's immune system against COVID-19. These plants were selected from 100 of the best-studied Philippine medicinal plants with antiviral and immunomodulatory properties. The general antiviral and specific anti-SARS-CoV-2 activities and immunomodulatory properties of the phytochemicals that these plants contained were searched. While many compounds assessed individually using in vitro and in silico techniques suggest potential anti-SARS-CoV-2 or immunomodulatory effects, this review sought to identify the medicinal plants which contain these compounds and which, based on literature, have the best potential application against COVID-19. These plants are Allium spp. bulbs (bawang), Andrographis paniculata (Burm.f.) Nees leaves (sinta), Cocos nucifera L. oil (niyog), Euphorbia hirta L. leaves (tawa-tawa), Euphorbia neriifolia L. leaves (sorosoro), Moringa oleifera Lam. leaves (malunggay), Ocimum basilicum L. leaves (balanoy), Piper nigrum L. seeds (paminta), Vitex negundo L. leaves (lagundi), and Zingiber officinale Roscoe rhizome (luya). This review provides a shortlist that can guide research on possible solutions to COVID-19 using Philippine medicinal plants.

Impact of COVID-19 on cash crops: the case of black pepper in Kerala

The nationwide lockdown which has been in force from 24th March 2020 due to COVID-19 pandemic had a severe economic impact on agriculture sector. This has been in spite of the exemptions given to the sector after two weeks of lockdown. The agriculture has been seen by many in the post-COVID scenario as the bright spot in the economy. But, the pepper crop is uniquely located in the sense that its consumption is largely driven by food processing industries which had been affected by the pandemic. Not only that the two back-to-back floods in 2018 and 2019 had severely affected the pepper production in Idukki district of Kerala which accounts for the largest production share. The district even faced a spate of farmer suicides in the recent times. This paper is an exploration into the various impacts of the present pandemic on the pepper economy of Kerala. It also tries to come up with some policy recommendations to revive the pepper production in the post-COVID economic structure.

Semi-Synthesis of N-Aryl Amide Analogs of Piperine from Piper nigrum and Evaluation of Their Antitrypanosomal, Antimalarial, and Anti-SARS-CoV-2 Main Protease Activities.

Piper nigrum, or black pepper, produces piperine, an alkaloid that has diverse pharmacological activities. In this study, N-aryl amide piperine analogs were prepared by semi-synthesis involving the saponification of piperine (1) to yield piperic acid (2) followed by esterification to obtain compounds 3, 4, and 5. The compounds were examined for their antitrypanosomal, antimalarial, and anti-SARS-CoV-2 main protease activities. The new 2,5-dimethoxy-substituted phenyl piperamide 5 exhibited the most robust biological activities with no cytotoxicity against mammalian cell lines, Vero and Vero E6, as compared to the other compounds in this series. Its half-maximal inhibitory concentration (IC50) for antitrypanosomal activity against Trypanosoma brucei rhodesiense was 15.46 ± 3.09 µM, and its antimalarial activity against the 3D7 strain of Plasmodium falciparum was 24.55 ± 1.91 µM, which were fourfold and fivefold more potent, respectively, than the activities of piperine. Interestingly, compound 5 inhibited the activity of 3C-like main protease (3CLPro) toward anti-SARS-CoV-2 activity at the IC50 of 106.9 ± 1.2 µM, which was threefold more potent than the activity of rutin. Docking and molecular dynamic simulation indicated that the potential binding of 5 in the 3CLpro active site had the improved binding interaction and stability. Therefore, new aryl amide analogs of piperine 5 should be investigated further as a promising anti-infective agent against human African trypanosomiasis, malaria, and COVID-19.

A REVIEW AND UPDATING OF THE KNOWLEDGE OF BIOCHEMICAL MECHANISMS OF PERFORMANCE ACTING SOME SPICES & MEDICINAL HERBALS FROM AYURVEDA PROTOCOL VS COVID-19

The publication and worldwide diffusion of the Ayurveda treatment of COVID-19 and the vital role that spices, and medicinal herbals play in this protocol, promoted by the Department of Health and Family Welfare of India (MoHFW), in the context of SARS-CoV2 infection. Encourage us to review updating the knowledge of these herbals' plants' biochemical mechanisms of action. Several biochemical mechanisms of action of spices have been studied and established in the context of COVID-19. It has been described that herbs act as blocking agonists of some cell receptors, such as the ACE2 receptor of the renin-angiotensin system and TRP receptors belonging to the superfamily of sensory neurons, responsible for symptoms the SARS-CoV2 virus. We also find widely recommended medicinal herbs such as Tinospora cordifolia and Withania somnifera in this protocol, which has been described to stimulate the immune system and, at the same time, increase the destructive capacity of macrophages and biochemically block the entry of SARS-CoV-2 to host cells. Other medicinal herbs recommended by the Ayurveda protocol such as Curcuma longa L, Cinnamomum camphora, Eucalyptus globulus, Allium sativum L, Piper nigrum, Glycyrrhiza glabra L, as well as being potent antioxidants and anti-inflammatory are traditionally selected as an adjuvant treatment indicated for "respiratory diseases" as in the current framework of the COVID-19 pandemic. This article explores the Ayurveda protocol and some recently recommended nutraceutical substances and spiced dietary guidelines, as an alternative treatment in concern to SARS-CoV2 infection, for the treatment of long-term side effects of the post-COVID syndrome.

Survey on the level of knowledge of medicinal plants used against Coronavirus disease, influenza and colds among travelers who came for the COVID-19 test at the Institut Pasteur de C..te d'Ivoire

Objective: This study was conducted to identify medicinal plants in the fight against Coronavirus disease, influenza and colds cited by travelers who came for their Covid test at the Institut Pasteur of C..te d'Ivoire. Methodology and Results: A semi-structured interview was conducted with 527 travelers from April 1 to June 30, 2021. The interviewed travelers were predominantly male (69.4%). Travelers going to France (28.46%) were the most numerous. The most represented age groups were 41-64 (43.83%) and 25-40 (43.26%). When the level of education is considered, the surveyed travelers have a higher level of education (89.94%). Entrepreneurs (13.85%), traders (12.66%), company directors (12.33%), students (8.54%) and health workers (6.45%) are the majority. Only 21.63% of travelers used traditional medicine in the last 12 months prior to the survey. Various plants are used to fight (33.43%) or prevent (56.57%) Coronavirus disease (7.02%), influenza (3.60%) and colds (2.84%). In total, 13 species of medicinal plants divided into 13 genera and 13 families were cited. Azadirachta indica (Meliaceae) with citation frequencies (cf) of 22%, Zingiber officinale (Zingiberaceae) with cf of 21% and Citrus limon (Rutaceae) with cf of 14% were the most cited species. Conclusion and application of results: These plants could be used for research and development of phytomedicines against Coronavirus, influenza and cold.

Evaluation of Efficacy and Safety of Clevira as an Add on Drug in Mild to Moderate COVID-19 Positive Patients- A Randomised Control Trial

Introduction: Coronavirus Disease 2019 (COVID-19) has caused a devastating pandemic. Despite the worldwide efforts to find a therapeutic strategy and prophylaxis, we have not attained a complete success. Hence, there exists an urgent need for development of alternative solutions from Ayurveda system of medicine for COVID-19. Aim: To evaluate clevira, a polyherbal ayurvedic formulation, for its efficacy and safety in treatment of mild to moderate COVID-19 patients as an add on drug. Materials and Methods: This randomised control trial was carried out from May 2020 to July 2020, in 100 patients (50 in test group and 50 in control group) confirmed with COVID-19 infection (mild to moderate cases) by Reverse Transcription Polymerase Chain Reaction (RT-PCR) at a tertiary care Government Medical College and Hospital in Chennai, India. The test group received tablet clevira orally twice daily after food, in the morning and night for 14 days, as an add on, in addition to standard care of treatment as received by the control group. The primary outcome was assessment of clinical recovery, proportion of patients with swabs negative for COVID-19 in RT-PCR and reduction of Viral cycle threshold ratio. The results of the both group were analysed and compared using Chi-square test and student's t-test. Results: Significant improvement (p-value=0.0338) was seen in patients on day 5, who got treated with clevira as add on drug. An 86% (43) of patients turned out to be COVID-19 RT-PCR test negative on day 5 while in the control group 66% (33) of patients turned out to be negative. There was a statistically significant difference (p-value=0.0196) between the test and control groups on comparing the mean difference in CT value results between day 1 and day 5. Clevira when given in addition to the standard of care, showed a significant improvement in signs and symptoms of COVID-19 infection. Conclusion: Clevira, with its polyherbal ingredients show a significant antiviral action against coronavirus when given in addition to the standard of care medications suggested by Indian Council of Medical Research (ICMR), over a period of 14 days in treatment of mild to moderate COVID-19 patients.

In silico and Molecular Docking Studies of Black Pepper Phyto-constituents against EmrD Efflux Pump of E. coli

Multidrug resistance (MDR) bacterial infection is the next pandemic waiting behind the COVID-19 with annual mortality rate 700000 worldwide. Among the MDR bacteria, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus faecium and Enterococcus faecalis are showing average resistance of 50 to 80% to ampicillin, amoxicillin, third-generation cephalosporin’s and fluoroquinolone and even to combinations antibiotics such as amoxicillin-clavulanic acid. To make the antibiotic resistance issue worst, pharmaceutical industry is reluctant to invest in research and development of new antibiotic typically due to low returns on investment. Accordingly, use of combination of two or more antibiotics or use of the antibiotic adjuvants are only available ways in combatting the ever growing Multidrug resistance (MDR) in bacteria. The present paper is designed to analyze the synergistic potential of black pepper phyto-constituents as the amoxicillin adjuvants in comparison with isolated piperine against the MDR E. coli. using in-silico molecular docking. The result indicates that binding energy (Kcal/mol) and torsion free energy (Kcal/mol) of piperine (-6.23, +0.89), beta caryophyllene (-6.36, +0.00), beta selinene (-6.93, +0.30), beta-Thujene (-5.42, +0.30) is less for the emrD efflux pump as compared to amoxicillin (-5.85, +2.93) respectively indicating strong inhibition for EmrD of MDR E-coli than amoxicillin. The results are also indicating that black pepper extract containing all aforementioned phyto-constituents has synergistic effect in comparison with isolated piperine against the MDR E. coli. ADMET of these phyto-constituents also indicates their safety profile in combination with amoxicillin.