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Repurposing pharmaceutical excipients as an antiviral agent against SARS-CoV-2.
Malani, M, Salunke, P, Kulkarni, S, Jain, GK, Sheikh, A, Kesharwani, P, Nirmal, J
Journal of biomaterials science. Polymer edition. 2022;(1):110-136
Abstract
The limited time indorsed to face the COVID-19 emergency and large number of deaths across the globe, poses an unrelenting challenge to find apt therapeutic approaches. However, lead candidate selection to phase III trials of new chemical entity is a time-consuming procedure, and not feasible in pandemic, such as the one we are facing. Drug repositioning, an exploration of existing drug for new therapeutic use, could be an effective alternative as it allows fast-track estimation in phase II-III trials, or even forthright compassionate use. Although, drugs repurposed for COVID-19 pandemic are commercially available, yet the evaluation of their safety and efficacy is tiresome and painstaking. In absence of any specific treatment the easy alternatives such as over the counter products, phytotherapies and home remedies have been largely adopted for prophylaxis and therapy as well. In recent years, it has been demonstrated that several pharmaceutical excipients possess antiviral properties making them prospective candidates against SARS-CoV-2. This review highlights the mechanism of action of various antiviral excipients and their propensity to act against SARs-CoV2. Though, repurposing of pharmaceutical excipients against COVID-19 has the edge over therapeutic agents in terms of safety, cost and fast-track approval trial burdened, this hypothesis needs to be experimentally verified for COVID-19 patients.
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Clinical features and mechanistic insights into drug repurposing for combating COVID-19.
Asrani, P, Tiwari, K, Eapen, MS, McAlinden, KD, Haug, G, Johansen, MD, Hansbro, PM, Flanagan, KL, Hassan, MI, Sohal, SS
The international journal of biochemistry & cell biology. 2022;:106114
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Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged from Wuhan in China before it spread to the entire globe. It causes coronavirus disease of 2019 (COVID-19) where mostly individuals present mild symptoms, some remain asymptomatic and some show severe lung inflammation and pneumonia in the host through the induction of a marked inflammatory 'cytokine storm'. New and efficacious vaccines have been developed and put into clinical practice in record time, however, there is a still a need for effective treatments for those who are not vaccinated or remain susceptible to emerging SARS-CoV-2 variant strains. Despite this, effective therapeutic interventions against COVID-19 remain elusive. Here, we have reviewed potential drugs for COVID-19 classified on the basis of their mode of action. The mechanisms of action of each are discussed in detail to highlight the therapeutic targets that may help in reducing the global pandemic. The review was done up to July 2021 and the data was assessed through the official websites of WHO and CDC for collecting the information on the clinical trials. Moreover, the recent research papers were also assessed for the relevant data. The search was mainly based on keywords like Coronavirus, SARS-CoV-2, drugs (specific name of the drugs), COVID-19, clinical efficiency, safety profile, side-effects etc.This review outlines potential areas for future research into COVID-19 treatment strategies.
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The potential role of resveratrol as supportive antiviral in treating conditions such as COVID-19 - A formulator's perspective.
van Brummelen, R, van Brummelen, AC
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112767
Abstract
With an increased transmissibility but milder form of disease of the omicron variant of COVID-19 and the newer antivirals often still out of reach of many populations, a refocus of the current treatment regimens is required. Safe, affordable, and available adjuvant treatments should also be considered and known drugs and substances need to be repurposed and tested. Resveratrol, a well-known antioxidant of natural origin, shown to act as an antiviral as well as playing a role in immune stimulation, down regulation of the pro-inflammatory cytokine release and reducing lung injury by reducing oxidative stress, is such an option. New initiatives and collaborations will however need to be found to unleash resveratrol's full potential in the pharmaceutical market.
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Coronavirus enzyme inhibitors-experimentally proven natural compounds from plants.
Park, J, Park, R, Jang, M, Park, YI, Park, Y
Journal of microbiology (Seoul, Korea). 2022;(3):347-354
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Abstract
Coronavirus disease (COVID-19) can cause critical conditions that require efficient therapeutics. Several medicines are derived from plants, and researchers are seeking natural compounds to ameliorate the symptoms of COVID-19. Viral enzymes are popular targets of antiviral medicines; the genome of coronaviruses encodes several enzymes, including RNA-dependent RNA polymerase and viral proteases. Various screening systems have been developed to identify potential inhibitors. In this review, we describe the natural compounds that have been shown to exert inhibitory effects on coronavirus enzymes. Although computer-aided molecular structural studies have predicted several antiviral compound candidates, the current review focuses on experimentally proven natural compounds.
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Emerging Roles of Vitamin D-Induced Antimicrobial Peptides in Antiviral Innate Immunity.
White, JH
Nutrients. 2022;(2)
Abstract
Vitamin D deficiency, characterized by low circulating levels of calcifediol (25-hydroxyvitamin D, 25D) has been linked to increased risk of infections of bacterial and viral origin. Innate immune cells produce hormonal calcitriol (1,25-dihydroxyvitamin D, 1,25D) locally from circulating calcifediol in response to pathogen threat and an immune-specific cytokine network. Calcitriol regulates gene expression through its binding to the vitamin D receptor (VDR), a ligand-regulated transcription factor. The hormone-bound VDR induces the transcription of genes integral to innate immunity including pattern recognition receptors, cytokines, and most importantly antimicrobial peptides (AMPs). Transcription of the human AMP genes β-defensin 2/defensin-β4 (HBD2/DEFB4) and cathelicidin antimicrobial peptide (CAMP) is stimulated by the VDR bound to promoter-proximal vitamin D response elements. HDB2/DEFB4 and the active form of CAMP, the peptide LL-37, which form amphipathic secondary structures, were initially characterized for their antibacterial actively. Notably, calcitriol signaling induces secretion of antibacterial activity in vitro and in vivo, and low circulating levels of calcifediol are associated with diverse indications characterized by impaired antibacterial immunity such as dental caries and urinary tract infections. However, recent work has also provided evidence that the same AMPs are components of 1,25D-induced antiviral responses, including those against the etiological agent of the COVID-19 pandemic, the SARS-CoV2 coronavirus. This review surveys the evidence for 1,25D-induced antimicrobial activity in vitro and in vivo in humans and presents our current understanding of the potential mechanisms by which CAMP and HBD2/DEFB4 contribute to antiviral immunity.
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Natural products can be used in therapeutic management of COVID-19: Probable mechanistic insights.
Ali, S, Alam, M, Khatoon, F, Fatima, U, Elasbali, AM, Adnan, M, Islam, A, Hassan, MI, Snoussi, M, De Feo, V
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112658
Abstract
The unexpected emergence of the new Coronavirus disease (COVID-19) has affected more than three hundred million individuals and resulted in more than five million deaths worldwide. The ongoing pandemic has underscored the urgent need for effective preventive and therapeutic measures to develop anti-viral therapy. The natural compounds possess various pharmaceutical properties and are reported as effective anti-virals. The interest to develop an anti-viral drug against the novel severe acute respiratory syndrome Coronavirus (SARS-CoV-2) from natural compounds has increased globally. Here, we investigated the anti-viral potential of selected promising natural products. Sources of data for this paper are current literature published in the context of therapeutic uses of phytoconstituents and their mechanism of action published in various reputed peer-reviewed journals. An extensive literature survey was done and data were critically analyzed to get deeper insights into the mechanism of action of a few important phytoconstituents. The consumption of natural products such as thymoquinone, quercetin, caffeic acid, ursolic acid, ellagic acid, vanillin, thymol, and rosmarinic acid could improve our immune response and thus possesses excellent therapeutic potential. This review focuses on the anti-viral functions of various phytoconstituent and alkaloids and their potential therapeutic implications against SARS-CoV-2. Our comprehensive analysis provides mechanistic insights into phytoconstituents to restrain viral infection and provide a better solution through natural, therapeutically active agents.
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Potential role of Drug Repositioning Strategy (DRS) for management of tauopathy.
Zaki, MO, Elsherbiny, DA, Salama, M, Azab, SS
Life sciences. 2022;:120267
Abstract
Tauopathy is a term that has been used to represent a pathological condition in which hyperphosphorylated tau protein aggregates in neurons and glia which results in neurodegeneration, synapse loss and dysfunction and cognitive impairments. Recently, drug repositioning strategy (DRS) becomes a promising field and an alternative approach to advancing new treatments from actually developed and FDA approved drugs for an indication other than the indication it was originally intended for. This paradigm provides an advantage because the safety of the candidate compound has already been established, which abolishes the need for further preclinical safety testing and thus substantially reduces the time and cost involved in progressing of clinical trials. In the present review, we focused on correlation between tauopathy and common diseases as type 2 diabetes mellitus and the global virus COVID-19 and how tau pathology can aggravate development of these diseases in addition to how these diseases can be a risk factor for development of tauopathy. Moreover, correlation between COVID-19 and type 2 diabetes mellitus was also discussed. Therefore, repositioning of a drug in the daily clinical practice of patients to manage or prevent two or more diseases at the same time with lower side effects and drug-drug interactions is a promising idea. This review concluded the results of pre-clinical and clinical studies applied on antidiabetics, COVID-19 medications, antihypertensives, antidepressants and cholesterol lowering drugs for possible drug repositioning for management of tauopathy.
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Home pharmacological therapy in early COVID-19 to prevent hospitalization and reduce mortality: Time for a suitable proposal.
Pandolfi, S, Chirumbolo, S, Ricevuti, G, Valdenassi, L, Bjørklund, G, Lysiuk, R, Doşa, MD, Lenchyk, L, Fazio, S
Basic & clinical pharmacology & toxicology. 2022;(2):225-239
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Abstract
The COVID-19 pandemic is a highly dramatic concern for mankind. In Italy, the pandemic exerted its major impact throughout the period of February to June 2020. To date, the awkward amount of more than 134,000 deaths has been reported. Yet, post-mortem autopsy was performed on a very modest number of patients who died from COVID-19 infection, leading to a first confirmation of an immune-thrombosis of the lungs as the major COVID-19 pathogenesis, likewise for SARS. Since then (June-August 2020), no targeted early therapy considering this pathogenetic issue was approached. The patients treated with early anti-inflammatory, anti-platelet, anticoagulant and antibiotic therapy confirmed that COVID-19 was an endothelial inflammation with immuno-thrombosis. Patients not treated or scarcely treated with the most proper and appropriate therapy and in the earliest, increased the hospitalization rate in the intensive care units and also mortality, due to immune-thrombosis from the pulmonary capillary district and alveoli. The disease causes widespread endothelial inflammation, which can induce damage to various organs and systems. Therapy must be targeted in this consideration, and in this review, we demonstrate how early anti-inflammatory therapy may treat endothelia inflammation and immune-thrombosis caused by COVID-19, by using drugs we are going to recommend in this paper.
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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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Antiviral activity of green tea and black tea polyphenols in prophylaxis and treatment of COVID-19: A review.
Mhatre, S, Srivastava, T, Naik, S, Patravale, V
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2021;:153286
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Abstract
BACKGROUND The rapid spread of novel coronavirus called SARS-CoV-2 or nCoV has caused countries all over the world to impose lockdowns and undertake stringent preventive measures. This new positive-sense single-stranded RNA strain of coronavirus spreads through droplets of saliva and nasal discharge. PURPOSE US FDA has authorized the emergency use of Remdesivir looking at the increasing number of cases of COVID-19, however there is still no drug approved to treat COVID-19. An alternative way of treatment could be the use of naturally derived molecules with known antiviral properties. METHOD We reviewed the antiviral activities of two polyphenols derived from tea, epigallocatechin-3-gallate (EGCG) from green tea and theaflavins from black tea. Both green tea and black tea polyphenols have been reported to exhibit antiviral activities against various viruses, especially positive-sense single-stranded RNA viruses. RESULTS Recent studies have revealed the possible binding sites present on SARS-CoV-2 and studied their interactions with tea polyphenols. EGCG and theaflavins, especially theaflavin-3,3'-digallate (TF3) have shown a significant interaction with the receptors under consideration in this review. Some docking studies further emphasize on the activity of these polyphenols against COVID-19. CONCLUSION This review summarizes the available reports and evidences which support the use of tea polyphenols as potential candidates in prophylaxis and treatment of COVID-19.