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Potential roles of medicinal plants for the treatment of viral diseases focusing on COVID-19: A review.
Adhikari, B, Marasini, BP, Rayamajhee, B, Bhattarai, BR, Lamichhane, G, Khadayat, K, Adhikari, A, Khanal, S, Parajuli, N
Phytotherapy research : PTR. 2021;(3):1298-1312
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Abstract
The whole world is entangled by the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), people are dying in thousands each day, and without an actual medication, it seems not possible for the bringing this global health crisis to a stop. Natural products have been in constant use since ancient times and are proven by time to be effective. Crude extract or pure compounds isolated from medicinal plants and/or herbs such as Artemisia annua, Agastache rugosa, Astragalus membranaceus, Cassia alata, Ecklonia cava, Gymnema sylvestre, Glycyrrhizae uralensis, Houttuynia cordata, Lindera aggregata, Lycoris radiata, Mollugo cerviana, Polygonum multiflorum, Pyrrosia lingua, Saposhnikoviae divaricate, Tinospora cordifolia etc. have shown promising inhibitory effect against coronavirus. Several molecules, including acacetin, amentoflavone, allicin, blancoxanthone, curcumin, daidzein, diosmin, epigallocatechin-gallate, emodin, hesperidin, herbacetin, hirsutenone, iguesterin, jubanine G, kaempferol, lycorine, pectolinarin, phloroeckol, silvestrol, tanshinone I, taxifolin, rhoifolin, xanthoangelol E, zingerol etc. isolated from plants could also be potential drug candidates against COVID-19. Moreover, these could also show promising inhibitory effects against influenza-parainfluenza viruses, respiratory syncytial virus, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have reported 93 antiviral drug candidates which could be a potential area of research in drug discovery.
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Possible Beneficial Actions of Caffeine in SARS-CoV-2.
Romero-Martínez, BS, Montaño, LM, Solís-Chagoyán, H, Sommer, B, Ramírez-Salinas, GL, Pérez-Figueroa, GE, Flores-Soto, E
International journal of molecular sciences. 2021;(11)
Abstract
The COVID-19 pandemic has established an unparalleled necessity to rapidly find effective treatments for the illness; unfortunately, no specific treatment has been found yet. As this is a new emerging chaotic situation, already existing drugs have been suggested to ameliorate the infection of SARS-CoV-2. The consumption of caffeine has been suggested primarily because it improves exercise performance, reduces fatigue, and increases wakefulness and awareness. Caffeine has been proven to be an effective anti-inflammatory and immunomodulator. In airway smooth muscle, it has bronchodilator effects mainly due to its activity as a phosphodiesterase inhibitor and adenosine receptor antagonist. In addition, a recent published document has suggested the potential antiviral activity of this drug using in silico molecular dynamics and molecular docking; in this regard, caffeine might block the viral entrance into host cells by inhibiting the formation of a receptor-binding domain and the angiotensin-converting enzyme complex and, additionally, might reduce viral replication by the inhibition of the activity of 3-chymotrypsin-like proteases. Here, we discuss how caffeine through certain mechanisms of action could be beneficial in SARS-CoV-2. Nevertheless, further studies are required for validation through in vitro and in vivo models.
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Unravelling high-affinity binding compounds towards transmembrane protease serine 2 enzyme in treating SARS-CoV-2 infection using molecular modelling and docking studies.
M, P, Reddy, GJ, Hema, K, Dodoala, S, Koganti, B
European journal of pharmacology. 2021;:173688
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Abstract
The coronavirus disease-19 (COVID-19) outbreak that is caused by a highly contagious severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a zoonotic pandemic, with approximately 24.5 million positive cases and 8.3 lakhs deaths globally. The lack of effective drugs or vaccine provoked the research for drug candidates that can disrupt the spread and progression of the virus. The identification of drug molecules through experimental studies is time-consuming and expensive, so there is a need for developing alternative strategies like in silico approaches which can yield better outcomes in less time. Herein, we selected transmembrane protease serine 2 (TMPRSS2) enzyme, a potential pharmacological target against SARS-CoV-2, involved in the spread and pathogenesis of the virus. Since 3D structure is not available for this protein, the present study aims at homology modelling and validation of TMPRSS2 using Swiss-model server. Validation of the modelled TMPRSS2 using various online tools confirmed model accuracy, topology and stereochemical plausibility. The catalytic triad consisting of Serine-441, Histidine-296 and Aspartic acid-345 was identified as active binding site of TMPRSS2 using existing ligands. Molecular docking studies of various drugs and phytochemicals against the modelled TMPRSS2 were performed using camostat as a standard drug. The results revealed eight potential drug candidates, namely nafamostat, meloxicam, ganodermanontriol, columbin, myricetin, proanthocyanidin A2, jatrorrhizine and baicalein, which were further studied for ADME/T properties. In conclusion, the study unravelled eight high affinity binding compounds, which may serve as potent antagonists against TMPRSS2 to impact COVID-19 drug therapy.
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SHARED: An International Collaboration to Unravel Hepatitis C Resistance.
Howe, AYM, Ceccherini-Silberstein, F, Dietz, J, Popping, S, Grebely, J, Rodrigo, C, Lennerstrand, J, Douglas, MW, Parczewsk, M, Harrigan, PR, et al
Viruses. 2021;(8)
Abstract
The advent of direct-acting antivirals (DAAs) has transformed the treatment landscape of hepatitis C [...].
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INEXAS: A Phase 2 Randomized Trial of On-demand Inhaled Interferon Beta-1a in Severe Asthmatics.
McCrae, C, Olsson, M, Gustafson, P, Malmgren, A, Aurell, M, Fagerås, M, Da Silva, CA, Cavallin, A, Paraskos, J, Karlsson, K, et al
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2021;(2):273-283
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Abstract
BACKGROUND Upper respiratory tract infections (URTIs) are important triggers for asthma exacerbations. We hypothesized that inhalation of the anti-viral cytokine, interferon (IFN)-β, during URTI, could prevent these exacerbations. OBJECTIVE To evaluate the efficacy of on-demand inhaled IFN-β1a (AZD9412) to prevent severe asthma exacerbations following symptomatic URTI. METHODS This was a randomized, double-blind, placebo-controlled trial in which patients with severe asthma (GINA 4-5; n = 121) reporting URTI symptoms were randomized to 14 days of once-daily nebulized AZD9412 or placebo. The primary endpoint was severe exacerbations during treatment. Secondary endpoints included 6-item asthma control questionnaire (ACQ-6) and lung function. Exploratory biomarkers included IFN-response markers in serum and sputum, blood leucocyte counts and serum inflammatory cytokines. RESULTS Following a pre-planned interim analysis, the trial was terminated early due to an unexpectedly low exacerbation rate. Asthma worsenings were generally mild and tended to peak at randomization, possibly contributing to the lack of benefit of AZD9412 on other asthma endpoints. Numerically, AZD9412 did not reduce severe exacerbation rate, ACQ-6, asthma symptom scores or reliever medication use. AZD9412 improved lung function (morning peak expiratory flow; mPEF) by 19.7 L/min. Exploratory post hoc analyses indicated a greater mPEF improvement by AZD9412 in patients with high blood eosinophils (>0.3 × 109 /L) at screening and low serum interleukin-18 relative change at pre-treatment baseline. Pharmacodynamic effect of AZD9412 was confirmed using IFN-response markers. CONCLUSIONS & CLINICAL RELEVANCE Colds did not have the impact on asthma patients that was expected and, due to the low exacerbation rate, the trial was stopped early. On-demand AZD9412 treatment did not numerically reduce the number of exacerbations, but did attenuate URTI-induced worsening of mPEF. Severe asthma patients with high blood eosinophils or low serum interleukin-18 response are potential subgroups for further investigation of inhaled IFN-β1a.
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Recommendations for Dosing of Repurposed COVID-19 Medications in Patients with Renal and Hepatic Impairment.
Marra, F, Smolders, EJ, El-Sherif, O, Boyle, A, Davidson, K, Sommerville, AJ, Marzolini, C, Siccardi, M, Burger, D, Gibbons, S, et al
Drugs in R&D. 2021;(1):9-27
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Abstract
INTRODUCTION In December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began, resulting in a number of antivirals and immune modulators being repurposed to treat the associated coronavirus disease 2019 (COVID-19). Many patients requiring treatment for COVID-19 may have either pre-existing renal or hepatic disease or experience acute renal/hepatic injury as a result of the acute infection. Altered renal or hepatic function can significantly affect drug concentrations of medications due to impaired drug metabolism and excretion, resulting in toxicity or reduced efficacy. The aim of this paper is to review the pharmacokinetics and available study data for the experimental COVID-19 therapies in patients with any degree of renal or hepatic impairment to make recommendations for dosing. METHODS COVID-19 agents included in these recommendations were listed as primaries on the University of Liverpool COVID-19 drug interaction website ( www.covid19-druginteractions.org ), initially identified from Clinicialtrials.gov and ChicCTR.org.cn. A literature search was performed using PubMed and EMBASE as well as product licences and pharmacokinetic databases. FINDINGS Remdesivir, dexamethasone, azithromycin, favipiravir, lopinavir/ritonavir, atazanavir, hydroxychloroquine, interferon beta, ribavirin, tocilizumab, anakinra and sarilumab were identified as experimental drugs being used in COVID-19 trials as of November 2020. Limited study data was found for these drugs in patients with renal or hepatic impairment for COVID-19 or other indications. Recommendations were made based on available data, consideration of pharmacokinetic properties (including variability), the dosing and anticipated treatment duration of each regimen in COVID-19 and known toxicities. CONCLUSION Dosing of drugs used to treat COVID-19 in patients with renal or hepatic impairment is complex. These recommendations were produced to provide guidance to clinicians worldwide who are treating patients with COVID-19, many of whom will have some degree of acute or chronic renal or hepatic impairment.
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Decoding the silent walk of COVID-19: Halting its spread using old bullets.
Kumar, M, Madan, J, Sodhi, RK, Singh, SB, Katyal, A
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2021;:110891
Abstract
Severe acute respiratory syndrome (SARS) develops within 3-14 days when CoV2 invades epithelial, myeloid cells in the nasopharynx and pneumocytes in the respiratory tract through angiotensin converting enzyme (ACE2). Infection swiftly disseminates to gastrointestinal, cardiovascular, renal organs as well as immune system to deregulate their normal functioning through unique and distinct mechanisms. The health system and economy has been intensely thwarted by the rapid spread and exorbitant mortality caused by COVID-19 disease across the globe. The acute progression of the disease and high infection rate pose an enormous challenge for its therapeutic management and critical care. The viral structure, genome and proteome have been deciphered which yielded cues for targeting already available therapeutic entities. More than 200 compounds have been screened and till date approximately 69 therapeutic agents are undergoing clinical trials across the world. Among these, remedesivir (RMD), chloroquine (CQ), hydroxychloroquine (HCQ), noscapine (NOS) and heparin have demonstrated fairly promising results in preclinical and clinical studies. Recently, RMD has been approved by USFDA for the management of COVID 19. However, intense research is going on to screen and ace the 'magic bullets' for the management of SARS-CoV2 infection worldwide. The current review illustrates the plausible therapeutic targets in SARS-CoV2 important for inhibition of virus cycle. In addition, the role of RMD, CQ, HCQ, NOS and heparin in combating infection has been addressed. The importance of vitamin C and D supplements as adjunct therapies in the prevention of SARS-CoV2 virus infection have also been summarized.
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Short-term and long-term safety and efficacy of tenofovir alafenamide, tenofovir disoproxil fumarate and entecavir treatment of acute-on-chronic liver failure associated with hepatitis B.
Li, J, Hu, C, Chen, Y, Zhang, R, Fu, S, Zhou, M, Gao, Z, Fu, M, Yan, T, Yang, Y, et al
BMC infectious diseases. 2021;(1):567
Abstract
BACKGROUND & AIMS There is limited evidence on the efficacy and safety of nucleos(t) ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF. METHODS Patients with HBV-related ACLF were recruited and received daily TAF (25 mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response. RESULTS Forty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short -term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported. CONCLUSIONS TAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF. TRIAL REGISTRATION This study is ongoing and is registered with ClinicalTrials.gov , NCT03640728 (05/02/2019).
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Nutraceuticals in the Prevention of Viral Infections, including COVID-19, among the Pediatric Population: A Review of the Literature.
Parisi, GF, Carota, G, Castruccio Castracani, C, Spampinato, M, Manti, S, Papale, M, Di Rosa, M, Barbagallo, I, Leonardi, S
International journal of molecular sciences. 2021;(5)
Abstract
In recent years, there has been a growth in scientific interest in nutraceuticals, which are those nutrients in foods that have beneficial effects on health. Nutraceuticals can be extracted, used for food supplements, or added to foods. There has long been interest in the antiviral properties of nutraceuticals, which are especially topical in the context of the ongoing COVID-19 pandemic. Therefore, the purpose of this review is to evaluate the main nutraceuticals to which antiviral roles have been attributed (either by direct action on viruses or by modulating the immune system), with a focus on the pediatric population. Furthermore, the possible applications of these substances against SARS-CoV-2 will be considered.
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A status report with critical analysis of research trends in exploring medicinal plants as antiviral: Let us dig into the history to predict the future.
Mukherjee, S, Chouhan, KBS, Tandey, R, Yadav, N, Dhobi, M, Mandal, V
Phytotherapy research : PTR. 2021;(8):4284-4296
Abstract
The review article serves as a mini directory of medicinal plants (662 medicinal plants have been identified) that have been investigated for antiviral property between 2015 and 2019. Data have been extracted from Scopus using specific keywords followed by manual sorting to avoid any duplication. Critical analyses of handpicked data have been presented. Mapping of medicinal plants, followed by critical analysis on the families and plant parts investigated in the said tenure, and its correlation with the participating countries and virus types have been critically analyzed. Interceptive role of phytochemicals in impeding viral replication has also been taken note of. Emphasis on India's exploration of various medicinal plants has also been given. Also presents a tutelage, which is likely to revive the interest in natural products for search of potential antivirals. This review is expected to serve as a rich data bank and as a guiding principle for researchers who are planning to explore medicinal plants in search for potential antiviral. It is time that researchers need to revisit their countries' own history of traditional medicine to predict something worthful in future.