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1.
Medicina (Kaunas) ; 59(4)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37109600

RESUMO

Background and Objectives: The study of clinical pharmacokinetics of inhaled antivirals is particularly important as it helps one to understand the therapeutic efficacy of these drugs and how best to use them in the treatment of respiratory viral infections such as influenza and the current COVID-19 pandemic. The article presents a systematic review of the available pharmacokinetic data of inhaled antivirals in humans, which could be beneficial for clinicians in adjusting doses for diseased populations. Materials and Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search was conducted using multiple databases, and studies were screened by two independent reviewers to assess their eligibility. Data were extracted from the eligible studies and assessed for quality using appropriate tools. Results: This systematic review evaluated the pharmacokinetic parameters of inhaled antiviral drugs. The review analyzed 17 studies, which included Zanamivir, Laninamivir, and Ribavirin with 901 participants, and found that the non-compartmental approach was used in most studies for the pharmacokinetic analysis. The outcomes of most studies were to assess clinical pharmacokinetic parameters such as the Cmax, AUC, and t1/2 of inhaled antivirals. Conclusions: Overall, the studies found that the inhaled antiviral drugs were well tolerated and exhibited favorable pharmacokinetic profiles. The review provides valuable information on the use of these drugs for the treatment of influenza and other viral respiratory infections.


Assuntos
COVID-19 , Influenza Humana , Humanos , Antivirais/uso terapêutico , Influenza Humana/tratamento farmacológico , Pandemias , Zanamivir/efeitos adversos
2.
Medicina (Kaunas) ; 59(4)2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37109718

RESUMO

(1) Background and Objectives: Pneumonia is a major cause of morbidity and mortality worldwide, including in Saudi Arabia, and the prevalence and etiology of the disease varies depending on the setting. The development of effective strategies can help reduce the adverse impact of this disease. Therefore, this systematic review was conducted to explore the prevalence and etiology of community-acquired and hospital-acquired pneumonia in Saudi Arabia, as well as their antimicrobial susceptibility. (2) Materials and Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations were followed for this systematic review. Several databases were used to perform a thorough literature search, and papers were then assessed for eligibility by two independent reviewers. The Newcastle-Ottawa Scale (NOS) was used to extract the data from the relevant research and evaluate its quality. (3) Results: This systematic review included 28 studies that highlighted the fact that gram-negative bacteria, particularly Acinetobacter spp. and Pseudomonas aeruginosa, were the common cause of hospital-acquired pneumonia, while Staphylococcus aureus and Streptococcus spp. were responsible for community-acquired pneumonia in children. The study also found that bacterial isolates responsible for pneumonia showed high resistance rates against several antibiotics, including cephalosporins and carbapenems. (4) Conclusions: In conclusion, the study found that different bacteria are responsible for community- and hospital-acquired pneumonia in Saudi Arabia. Antibiotic resistance rates were high for several commonly used antibiotics, highlighting the need for rational antibiotic use to prevent further resistance. Moreover, there is a need to conduct more regular multicenter studies to assess etiology, resistance, and susceptibility patterns of pneumonia-causing pathogens in Saudi Arabia.


Assuntos
Antibacterianos , Pneumonia , Criança , Humanos , Prevalência , Arábia Saudita/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pneumonia/epidemiologia , Pneumonia/etiologia , Pneumonia/tratamento farmacológico , Hospitais
3.
Curr Issues Mol Biol ; 44(7): 2887-2902, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35877423

RESUMO

Diabetic nephropathy (DN) is a serious kidney illness characterized by proteinuria, glomerular enlargement, reduced glomerular filtration, and renal fibrosis. DN is the most common cause of end-stage kidney disease, accounting for nearly one-third of all cases of diabetes worldwide. Hyperglycemia is a major factor in the onset and progression of diabetic nephropathy. Many contemporary medicines are derived from plants since they have therapeutic properties and are relatively free of adverse effects. Glycosides, alkaloids, terpenoids, and flavonoids are among the few chemical compounds found in plants that are utilized to treat diabetic nephropathy. The purpose of this review was to consolidate information on the clinical and pharmacological evidence supporting the use of a variety of medicinal plants to treat diabetic nephropathy.

4.
Molecules ; 27(9)2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35566101

RESUMO

COVID-19 has had an impact on human quality of life and economics. Scientists have been identifying remedies for its prevention and treatment from all possible sources, including plants. Nigella sativa L. (NS) is an important medicinal plant of Islamic value. This review highlights the anti-COVID-19 potential, clinical trials, inventions, and patent literature related to NS and its major chemical constituents, like thymoquinone. The literature was collected from different databases, including Pubmed, Espacenet, and Patentscope. The literature supports the efficacy of NS, NS oil (NSO), and its chemical constituents against COVID-19. The clinical data imply that NS and NSO can prevent and treat COVID-19 patients with a faster recovery rate. Several inventions comprising NS and NSO have been claimed in patent applications to prevent/treat COVID-19. The patent literature cites NS as an immunomodulator, antioxidant, anti-inflammatory, a source of anti-SARS-CoV-2 compounds, and a plant having protective effects on the lungs. The available facts indicate that NS, NSO, and its various compositions have all the attributes to be used as a promising remedy to prevent, manage, and treat COVID-19 among high-risk people as well as for the therapy of COVID-19 patients of all age groups as a monotherapy or a combination therapy. Many compositions of NS in combination with countless medicinal herbs and medicines are still unexplored. Accordingly, the authors foresee a bright scope in developing NS-based anti-COVID-19 composition for clinical use in the future.


Assuntos
Tratamento Farmacológico da COVID-19 , Nigella sativa , Plantas Medicinais , Humanos , Invenções , Nigella sativa/química , Qualidade de Vida , SARS-CoV-2
5.
Int J Mol Sci ; 22(21)2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34769383

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains spike proteins that assist the virus in entering host cells. In the absence of a specific intervention, efforts are afoot throughout the world to find an effective treatment for SARS-CoV-2. Through innovative techniques, monoclonal antibodies (MAbs) are being designed and developed to block a particular pathway of SARS-CoV-2 infection. More than 100 patent applications describing the development of MAbs and their application against SARS-CoV-2 have been registered. Most of them target the receptor binding protein so that the interaction between virus and host cell can be prevented. A few monoclonal antibodies are also being patented for the diagnosis of SARS-CoV-2. Some of them, like Regeneron® have already received emergency use authorization. These protein molecules are currently preferred for high-risk patients such as those over 65 years old with compromised immunity and those with metabolic disorders such as obesity. Being highly specific in action, monoclonal antibodies offer one of the most appropriate interventions for both the prevention and treatment of SARS-CoV-2. Technological advancement has helped in producing highly efficacious MAbs. However, these agents are known to induce immunogenic and non-immunogenic reactions. More research and testing are required to establish the suitability of administering MAbs to all patients at risk of developing a severe illness. This patent study is focused on MAbs as a therapeutic option for treating COVID-19, as well as their invention, patenting information, and key characteristics.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Enzima de Conversão de Angiotensina 2/imunologia , Animais , Anticorpos Monoclonais/imunologia , COVID-19/diagnóstico , COVID-19/virologia , Proteínas M de Coronavírus/imunologia , Humanos , Patentes como Assunto , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/imunologia
6.
Molecules ; 26(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34641339

RESUMO

The COVID-19 pandemic needs no introduction at present. Only a few treatments are available for this disease, including remdesivir and favipiravir. Accordingly, the pharmaceutical industry is striving to develop new treatments for COVID-19. Molnupiravir, an orally active RdRp inhibitor, is in a phase 3 clinical trial against COVID-19. The objective of this review article is to enlighten the researchers working on COVID-19 about the discovery, recent developments, and patents related to molnupiravir. Molnupiravir was originally developed for the treatment of influenza at Emory University, USA. However, this drug has also demonstrated activity against a variety of viruses, including SARS-CoV-2. Now it is being jointly developed by Emory University, Ridgeback Biotherapeutics, and Merck to treat COVID-19. The published clinical data indicate a good safety profile, tolerability, and oral bioavailability of molnupiravir in humans. The patient-compliant oral dosage form of molnupiravir may hit the market in the first or second quarter of 2022. The patent data of molnupiravir revealed its granted compound patent and process-related patent applications. We also anticipate patent filing related to oral dosage forms, inhalers, and a combination of molnupiravir with marketed drugs like remdesivir, favipiravir, and baricitinib. The current pandemic demands a patient compliant, safe, tolerable, and orally effective COVID-19 treatment. The authors believe that molnupiravir meets these requirements and is a breakthrough COVID-19 treatment.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Citidina/análogos & derivados , Descoberta de Drogas , Hidroxilaminas/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Administração Oral , Animais , Antivirais/administração & dosagem , Antivirais/química , Ensaios Clínicos como Assunto , Citidina/administração & dosagem , Citidina/química , Citidina/uso terapêutico , Humanos , Hidroxilaminas/administração & dosagem , Hidroxilaminas/química , Patentes como Assunto , DNA Polimerase Dirigida por RNA/metabolismo , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/química , Inibidores da Transcriptase Reversa/uso terapêutico , SARS-CoV-2/enzimologia , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/metabolismo
7.
J Biomol Struct Dyn ; 42(3): 1307-1318, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37139557

RESUMO

Ubiquitin specific protease 30 (USP30) has been attributed to mitochondrial dysfunction and impediment of mitophagy in Parkinson's disease (PD). This happens once ubiquitin that supposed to bind with deformed mitochondria at the insistence of Parkin, it's been recruited by USP30 via the distal ubiquitin binding domain. This is a challenge when PINK1 and Parkin loss their functions due to mutation. Although, there are reports on USP30s' inhibitors but no study on the repurposing of inhibitors approved against MMP-9 and SGLT-2 as potential inhibitors of USP30 in PD. Thus, the highlight therein, is to repurpose approved inhibitors of MMP-9 and SGLT-2 against USP30 in PD using extensive computational modelling framework. 3D structures of Ligands and USP30 were obtained from PubChem and protein database (PDB) servers respectively, and were subjected to molecular docking, ADMET evaluation, DFT calculation, molecular dynamics simulation (MDS) and free energy calculations. Out of the 18 drugs, 2 drugs showed good binding affinity to the distal ubiquitin binding domain, moderate pharmacokinetic properties and good stability. The findings showed canagliflozin and empagliflozin as potential inhibitors of USP30. Thus, we present these drugs as repurposing candidates for the treatment of PD. However, the findings in this current study needs to be validated experimentally.Communicated by Ramaswamy H. Sarma.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/genética , Metaloproteinase 9 da Matriz , Simulação de Acoplamento Molecular , Reposicionamento de Medicamentos , Proteínas Quinases/metabolismo , Proteínas Mitocondriais/química , Tioléster Hidrolases/química , Tioléster Hidrolases/genética , Tioléster Hidrolases/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina/metabolismo , Proteases Específicas de Ubiquitina/metabolismo
8.
J Biomol Struct Dyn ; : 1-21, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517058

RESUMO

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by the neoplastic transformation of hematopoietic stem cells, driven by the Philadelphia (Ph) chromosome resulting from a translocation between chromosomes 9 and 22. This Ph chromosome harbors the breakpoint cluster region (BCR) and the Abelson (ABL) oncogene (BCR-ABL1) which have a constitutive tyrosine kinase activity. However, the tyrosine kinase activity of BCR-ABL1 have been identified as a key player in CML initiation and maintenance through c-Abl kinase. Despite advancements in tyrosine kinase inhibitors, challenges such as efficacy, safety concerns, and recurring drug resistance persist. This study aims to discover potential c-Abl kinase inhibitors from plant compounds with anti-leukemic properties, employing drug-likeness assessment, molecular docking, in silico pharmacokinetics (ADMET) screening, density function theory (DFT), and molecular dynamics simulations (MDS). Out of 58 screened compounds for drug-likeness, 44 were docked against c-Abl kinase. The top hit compound (isovitexin) and nilotinib (control drug) were subjected to rigorous analyses, including ADMET profiling, DFT evaluation, and MDS for 100 ns. Isovitexin demonstrated a notable binding affinity (-15.492 kcal/mol), closely comparable to nilotinib (-16.826 kcal/mol), showcasing a similar binding pose and superior structural stability and reactivity. While these findings suggest isovitexin as a potential c-Abl kinase inhibitor, further validation through urgent in vitro and in vivo experiments is imperative. This research holds promise for providing an alternative avenue to address existing CML treatment and management challenges.Communicated by Ramaswamy H. Sarma.

9.
Pharmaceutics ; 15(2)2023 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-36839940

RESUMO

A mucoadhesive microemulsion of lipophilic silymarin (SLMMME) was developed to treat Parkinson's disease (PD). Optimization of the SLM microemulsion (ME) was performed using Central Composite Design (CCD). The composition of oil, surfactant, co-surfactant, and water was varied, as per the design, to optimize their ratio and achieve desirable droplet size, zeta potential, and drug loading. The droplet size, zeta potential, and drug loading of optimized SLMME were 61.26 ± 3.65 nm, -24.26 ± 0.2 mV, and 97.28 ± 4.87%, respectively. With the addition of chitosan, the droplet size and zeta potential of the developed ME were both improved considerably. In vitro cell toxicity investigations on a neuroblastoma cell line confirmed that SLMMME was non-toxic and harmless. In comparison to ME and drug solution, mucoadhesive ME had the most flow through sheep nasal mucosa. Further, the in vitro release showed significantly higher drug release, and diffusion of the SLM loaded in MEs than that of the silymarin solution (SLMS). The assessment of behavioral and biochemical parameters, as well as inflammatory markers, showed significant (p < 0.05) amelioration in their level, confirming the significant improvement in neuroprotection in rats treated with SLMMME compared to rats treated with naïve SLM.

10.
Biomedicines ; 11(2)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36830816

RESUMO

The monkeypox disease (MPX) outbreak of 2022 has been reported in more than one hundred countries and is becoming a global concern. Unfortunately, only a few treatments, such as tecovirimat (TCV), are available against MPX. Brincidofovir (BCV) is a United States Food and Drug Administration (USFDA)-approved antiviral against smallpox. This article reviews the potential of BCV for treating MPX and other Orthopoxvirus (OPXVs) diseases. The literature for this review was collected from PubMed, authentic websites (USFDA, Chimerix), and freely available patent databases (USPTO, Espacenet, and Patentscope). BCV (a lipophilic derivative of cidofovir) has been discovered and developed by Chimerix Incorporation, USA. Besides smallpox, BCV has also been tested clinically for various viral infections (adenovirus, cytomegalovirus, ebola virus, herpes simplex virus, and double-stranded DNA virus). Many health agencies and reports have recommended using BCV for MPX. However, no health agency has yet approved BCV for MPX. Accordingly, the off-label use of BCV is anticipated for MPX and various viral diseases. The patent literature revealed some important antiviral compositions of BCV. The authors believe there is a huge opportunity to create novel, inventive, and patentable BCV-based antiviral therapies (new combinations with existing antivirals) for OPXVs illnesses (MPX, smallpox, cowpox, camelpox, and vaccinia). It is also advised to conduct drug interaction (food, drug, and disease interaction) and drug resistance investigations on BCV while developing its combinations with other medications. The BCV-based drug repurposing options are also open for further exploration. BCV offers a promising opportunity for biosecurity against OPXV-based bioterrorism attacks and to control the MPX outbreak of 2022.

11.
Biomedicines ; 11(2)2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36831009

RESUMO

On a global scale, lung cancer is acknowledged to be the major driver of cancer death attributable to treatment challenges and poor prognosis. Classical cancer treatment regimens, such as chemotherapy or radiotherapy, can be used to treat lung cancer, but the appended adverse effects limit them. Because of the numerous side effects associated with these treatment modalities, it is crucial to strive to develop novel and better strategies for managing lung cancer. Attributes such as enhanced bioavailability, better in vivo stability, intestinal absorption pattern, solubility, prolonged and targeted distribution, and the superior therapeutic effectiveness of numerous anticancer drugs have all been boosted with the emergence of nano-based therapeutic systems. Lipid-based polymeric and inorganic nano-formulations are now being explored for the targeted delivery of chemotherapeutics for lung cancer treatment. Nano-based approaches are pioneering the route for primary and metastatic lung cancer diagnosis and treatment. The implementation and development of innovative nanocarriers for drug administration, particularly for developing cancer therapies, is an intriguing and challenging task in the scientific domain. The current article provides an overview of the delivery methods, such as passive and active targeting for chemotherapeutics to treat lung cancer. Combinatorial drug therapy and techniques to overcome drug resistance in lung cancer cells, as potential ways to increase treatment effectiveness, are also discussed. In addition, the clinical studies of the potential therapies at different stages and the associated challenges are also presented. A summary of patent literature has also been included to keep readers aware of the new and innovative nanotechnology-based ways to treat lung cancer.

12.
Healthcare (Basel) ; 11(8)2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37107916

RESUMO

The symptoms of psychiatric infirmities have variability, and selected drug regimens for mental illness are comparatively complex and individualized; therefore, pharmacy services vary with respect to patients, diseases, healthcare settings, community structures, and countries. Clinical pharmacy services for mental health (MH) are continuously being upgraded. A structured search of the literature was performed in the Cochrane, PubMed (Medline), PsycINFO, Google scholar, Scopus, Science Direct, and Springer Links databases. The title and abstract of each retrieved article were evaluated for relevance. To remove uncertainty and ambiguity, the full-text articles were retrieved and examined for relevance. The articles were further assessed on the basis of inclusion and exclusion criteria. Narrative synthesis was performed, creating new categories and relevant subcategories and further subsections. The articles and the results were assessed for quality and bias. Pharmacists have a range of expertise in psychiatric care. The services can be classified as conventional, extended, and advanced pharmacy services. Conventional services include the quality use of medicines in healthcare settings and medication support services in communities that ensure medication adherence. Pharmacists perform extended roles in collaborative medication therapy management, multidisciplinary community mental health teams, collaborative care, patient education, home medication review, hospital-to-home transit, and screening services. In the USA, the role of pharmacists was advanced by prescribing as collaborative and interim prescribers. Australia launched an accredited program for psychiatric first-aid pharmacists. Pharmacists can provide mental care to rural populations using health technology. The role of pharmacists in MH is appreciated either independently or as a team member. Patients and healthcare providers rank the services of pharmacists in MH highly. Still, there is a margin for improvement in the training of pharmacists. Pharmacists cannot provide sufficient time to their patients. Public awareness about the role of pharmacists in MH needs more attention. Moreover, the training of psychiatric pharmacists should be standardized around the world.

13.
Curr Neuropharmacol ; 21(7): 1558-1574, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35950245

RESUMO

Quercetin (Qu), a dietary flavonoid, is obtained from many fruits and vegetables such as coriander, broccoli, capers, asparagus, onion, figs, radish leaves, cranberry, walnuts, and citrus fruits. It has proven its role as a nutraceutical owing to numerous pharmacological effects against various diseases in preclinical studies. Despite these facts, Qu and its nanoparticles are less explored in clinical research as a nutraceutical. The present review covers various neuroprotective actions of Qu against various neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis. A literature search was conducted to systematically review the various mechanistic pathways through which Qu elicits its neuroprotective actions and the challenges associated with raw Qu that compromise therapeutic efficacy. The nanoformulations developed to enhance Qu's therapeutic efficacy are also covered. Various ongoing/completed clinical trials related to Qu in treating various diseases, including NDs, are also tabulated. Despite these many successes, the exploration of research on Qu-loaded nanoformulations is limited mostly to preclinical studies, probably due to poor drug loading and stability of the formulation, time-consuming steps involved in the formulation, and their poor scale-up capacity. Hence, future efforts are required in this area to reach Qu nanoformulations to the clinical level.


Assuntos
Nanopartículas , Doenças Neurodegenerativas , Humanos , Quercetina/uso terapêutico , Quercetina/farmacologia , Doenças Neurodegenerativas/tratamento farmacológico
14.
Expert Opin Ther Pat ; 32(5): 591-604, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35220857

RESUMO

INTRODUCTION: Leishmaniasis is a neglected tropical infectious disease. The available limited therapeutic options for leishmaniasis are inadequate due to their poor pharmacokinetic profile, resistance, toxicity, high cost, and compliance problems. This warrants identification of new targets for the development of safer and effective anti-Leishmania therapy. The kinetoplastid specific proteasome (KSP) is a novel validated target to develop drugs against leishmaniasis. AREA COVERED: This review focuses on all the published patent applications and granted patents related to the studied small molecules as KSP inhibitors (KSPIs) against Leishmania from 1998 to 31 December 2021. EXPERT OPINION: A little amount of work has been done on KSPIs, but the study results are quite encouraging. LXE408 and GSK3494245 are two KSPIs in different phases of clinical trials. Some other small molecules have also shown KSP inhibitory potential, but they are not in clinical trials. The KSPIs are promising next-generation orally active patient compliant drugs against kinetoplastid diseases, including leishmaniasis. However, the main challenge to discover the KSPIs will be the resistance development and their selectivity against the proteasome of eukaryotic cells.


Assuntos
Antiprotozoários , Leishmaniose , Antiprotozoários/farmacologia , Humanos , Leishmaniose/tratamento farmacológico , Oxazóis , Patentes como Assunto , Complexo de Endopeptidases do Proteassoma , Inibidores de Proteassoma/efeitos adversos , Pirimidinas
15.
Antioxidants (Basel) ; 11(5)2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35624740

RESUMO

Quercetin is a phenolic flavonol compound with established antioxidant, anti-inflammatory, and immuno-stimulant properties. Recent studies demonstrate the potential of quercetin against COVID-19. This article highlighted the prophylactic/therapeutic potential of quercetin against COVID-19 in view of its clinical studies, inventions, and patents. The literature for the subject matter was collected utilizing different databases, including PubMed, Sci-Finder, Espacenet, Patentscope, and USPTO. Clinical studies expose the potential of quercetin monotherapy, and also its combination therapy with other compounds, including zinc, vitamin C, curcumin, vitamin D3, masitinib, hydroxychloroquine, azithromycin, and ivermectin. The patent literature also examines claims that quercetin containing nutraceuticals, pharmaceuticals, and dietary supplements, alone or in combination with other drugs/compounds, including favipiravir, remdesivir, molnupiravir, navitoclax, dasatinib, disulfiram, rucaparib, tamarixin, iota-carrageenan, and various herbal extracts (aloe, poria, rosemary, and sphagnum) has potential for use against COVID-19. The literature reveals that quercetin exhibits anti-COVID-19 activity because of its inhibitory effect on the expression of the human ACE2 receptors and the enzymes of SARS-CoV-2 (MPro, PLPro, and RdRp). The USFDA designated quercetin as a "Generally Recognized as Safe" substance for use in the food and beverage industries. It is also an inexpensive and readily available compound. These facts increase the possibility and foreseeability of making novel and economical drug combinations containing quercetin to prevent/treat COVID-19. Quercetin is an acidic compound and shows metabolic interaction with some antivirals, antibiotics, and anti-inflammatory agents. Therefore, the physicochemical and metabolic drug interactions between quercetin and the combined drugs/compounds must be better understood before developing new compositions.

16.
Saudi J Biol Sci ; 29(5): 3326-3337, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35185356

RESUMO

COVID-19 (coronavirus disease-2019) is a contagious illness that has been declared a global epidemic by the World Health Organization (WHO). The coronavirus causes diseases ranging in severity from the common cold to severe respiratory diseases and death. Coronavirus primarily affects blood pressure by attaching to the angiotensin converting enzyme 2 (ACE 2) receptor. This virus has an impact on multiple organ systems, including the central nervous system, immune system, cardiovascular system, peripheral nervous system, gastrointestinal tract, endocrine system, urinary system, skin, and pregnancy. For the prevention of COVID-19, various vaccines such as viral-like particle vaccines, entire inactivated virus vaccines, viral vector vaccines, live attenuated virus vaccines, subunit vaccines, RNA vaccines, and DNA vaccines are now available. Some of the COVID-19 vaccines are reported to cause a variety of adverse effects that range from mild to severe in nature. SARS-CoV-2 replication is controlled by the RNA-Dependent RNA-Polymerase enzyme (RdRp). The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection. RdRp inhibitors, such as remdesivir (an anti-Ebola virus experimental drug) and favipiravir (an anti-influenza drug), inhibit RdRp and thus slow the progression of COVID-19 and associated clinical symptoms, as well as significantly shorten recovery time. Molnupiravir, an orally active RdRp inhibitor and noval broad spectrum antiviral agent, is an isopropyl pro-drug of EIDD-1931 for emergency use. Galidesivir's in vitro and in vivo activities are limited to RNA of human public health concern. Top seeds for antiviral treatments with high potential to combat the SARS-CoV-2 strain include guanosine derivatives (IDX-184), setrobuvir, and YAK. The goal of this review is to compile scattered information on available COVID-19 vaccines and other treatments for protecting the human body from their harmful effects and to provide options for making better choices in a timely manner.

17.
Pharmaceuticals (Basel) ; 15(2)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35215241

RESUMO

Human African trypanosomiasis (HAT or 'sleeping sickness') is a neglected tropical disease. If untreated, it is always fatal and leads to death. A few treatments are available for HAT, but most of them require a skilled professional, which increases the financial burden on the patient. Recently, fexinidazole (FEX) has been approved by the European Medicine Agency (EMA) and the United States Food and Drug Administration (USFDA) as the first all-oral therapy for the treatment of stage-1 (hemolymphatic) as well as stage-2 (meningoencephalitic) of HAT. Before the FEX approval, there were separate treatments for stage-1 and stage-2 of HAT. This study reviews the discovery, development timeline, inventions, and patent literature of FEX. It was first approved by EMA and USFDA in 2018 and 2021, respectively. FEX was also added to the World Health Organization's list of essential drugs in 2019. The patent literature search revealed many types of patents/patent applications (compound, salt, process, method of treatment, drug combinations, and compositions) related to FEX, which have been summarized in this article. The authors foresee a great scope to develop more inventions based on FEX (novel salts, polymorphs, drug conjugates, cyclodextrin complex, etc.) for the treatment of many protozoal diseases (Leishmaniasis and Chagas disease), inflammatory diseases, and other microbial infections. New combinations of FEX with other treatments of HAT may also provide fruitful results. This review might be useful to the scientists working on the HAT and other neglected diseases to develop novel inventions and innovations of therapeutic relevance.

18.
Nutrients ; 14(6)2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35334884

RESUMO

Zinc is an essential nutrient for human health; it is involved in the catalytic, structural, and regulatory functions of the human cellular system. Different compositions of zinc, as well as its pharmaceutically acceptable salts, are available on the market. Recent studies have demonstrated the role of zinc in combating COVID-19. It has been determined that zinc prevents the entry of SARS-CoV-2 into cells by lowering the expression of ACE-2 receptors and inhibiting the RNA-dependent RNA polymerase of SARS-CoV-2. Zinc also prevents the cytokine storm that takes place after the entry of SARS-CoV-2 into the cell, via its anti-inflammatory activity. The authors believe that no study has yet been published that has reviewed the trends, inventions, and patent literature of zinc compositions to treat/prevent COVID-19. Accordingly, this review has been written in order to fill this gap in the literature. The information about the clinical studies and the published patents/patent applications was retrieved from different databases. This review covers patent literature on zinc compositions up to 31 January 2022. Many important patents/patent applications for zinc-based compositions filed by innovative universities and industries were identified. The patent literature revealed zinc compositions in combination with zinc ionophores, antioxidants, antivirals, antibiotics, hydroxychloroquine, heparin, ivermectin, and copper. Most of these studies were supported by clinical trials. The patent literature supports the potential of zinc and its pharmaceutical compositions as possible treatments for COVID-19. The authors believe that countless zinc-based compositions are still unexplored, and there is an immense opportunity to evaluate a considerable number of the zinc-based compositions for use against COVID-19.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Invenções , COVID-19/prevenção & controle , Humanos , Preparações Farmacêuticas , SARS-CoV-2 , Zinco/uso terapêutico
19.
PeerJ ; 10: e13219, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35415012

RESUMO

Background: Coronavirus infection (COVID-19) has resulted in an unprecedented number of human deaths and economic losses. Analyzing the role of disease in different groups of people is useful for determining the burden of disease. As a result, the purpose of this study was to investigate the influence of COVID-19 on the Saudi Arabian population's quality of life, with a particular emphasis on the likely fall in their life expectancy. Methods: A cross-sectional and retrospective analysis of 2,988 patients' databases was performed to assess COVID-19-induced mortality and complications in the community. The data was gathered from official websites that track the disease's impact daily between July and October 2021. On the acquired data, disability-adjusted life years (DALYs) and relative risk analysis were performed. The data was statistically analyzed using SPSS IBM 25. The Pearson's correlation test was used to examine the relationship between age and disease impact. The significance of the findings was determined by using a P value of less than 0.05. Results: The data from the study indicated that the positive test rate, infection rate, and mortality rate in the population were 1.84% [+0.11/-0.39 of 95% confidence interval (CI)], 1.54% (+0.38/-0.52 of CI), and 1.59% (+0.4/-0.7 of CI), respectively. Highest percentage of mortality was observed in Riyadh (17%), followed by Jeddah (8.7%) and Makkah (7.5%). The DALYs/100,000 inhabitants increased progressively as the age of the population increased, and the highest value was found for those over 70 years old (25.73 ± 2.09). Similarly, the risk outcome (55%) increased significantly (p = 0.037) from 40 years onwards, and the maximum was observed at above 70 years (184%, p = 0.006). The correlation analysis indicated a significant association (p = 0.032) between age and COVID-19 induced mortality from the 40-year-old population onwards. Conclusion: The current study found that the COVID-19 load in Saudi Arabia was comparable to that in nations that were said to have performed well during the pandemic. DALYs increased from 40 years to 60 years, although people over 60 years had a lower life expectancy and were more susceptible to infection. After 60 years, the occurrence of numerous co-morbid illnesses may have added to the population's burden of COVID-19. Further research in this area may yield a more precise estimate of the COVID-19-induced burden on the entire population.


Assuntos
COVID-19 , Humanos , Idoso , Adulto , Arábia Saudita/epidemiologia , COVID-19/epidemiologia , Qualidade de Vida , Estudos Retrospectivos , Estudos Transversais , Carga Global da Doença
20.
J Infect Public Health ; 15(11): 1225-1233, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36265330

RESUMO

Selenium is an indispensable trace element for all living organisms. It is an essential structural component of several selenium-dependent enzymes, which support the human body's defense mechanism. Recently, the significance of selenium in preventing/treating COVID-19 has been documented in the literature. This review highlights the clinical studies, compositions, and patent literature on selenium to prevent/treat COVID-19. Selenium exerts its anti-COVID-19 action by reducing oxidative stress, declining the expression of the ACE-2 receptor, lowering the discharge of pro-inflammatory substances, and inhibiting the 3CLPro (main protease) and PLpro enzyme of SARS-CoV-2. The data of clinical studies, inventive compositions, and patent literature revealed that selenium monotherapy and its compositions with other nutritional supplements/drugs (vitamin, iron, zinc, copper, ferulic acid, resveratrol, spirulina, N-acetylcysteine, fish oil, many herbs, doxycycline, azithromycin, curcumin, quercetin, etc.,) might be practical to prevent/treat COVID-19. The studies have also suggested a correlation between COVID-19 and selenium deficiency. This indicates that adequate selenium supplementation may provide promising treatment outcomes in COVID-19 patients. The authors foresee the development and commercialization of Selenium-based compositions and dosage forms (spray, inhalers, control release dosage forms, etc.) to battle COVID-19. We also trust that numerous selenium-based compositions are yet to be explored. Accordingly, there is good scope for scientists to work on developing novel and inventive selenium-based compositions to fight against COVID-19. However, there is also a need to consider the narrow therapeutic window and chemical interaction of selenium before developing selenium-based compositions.


Assuntos
COVID-19 , Selênio , Humanos , Selênio/uso terapêutico , SARS-CoV-2 , Vitaminas , Suplementos Nutricionais
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