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1.
Infectious disorders drug targets ; 2023.
Article in English | EuropePMC | ID: covidwho-2197836
2.
Front Chem ; 10: 964446, 2022.
Article in English | MEDLINE | ID: covidwho-2089818

ABSTRACT

SARS-CoV-2 triggered a worldwide medical crisis, affecting the world's social, emotional, physical, and economic equilibrium. However, treatment choices and targets for finding a solution to COVID-19's threat are becoming limited. A viable approach to combating the threat of COVID-19 is by unraveling newer pharmacological and therapeutic targets pertinent in the viral survival and adaptive mechanisms within the host biological milieu which in turn provides the opportunity to discover promising inhibitors against COVID-19. Therefore, using high-throughput virtual screening, manually curated compounds library from some medicinal plants were screened against four main drivers of SARS-CoV-2 (spike glycoprotein, PLpro, 3CLpro, and RdRp). In addition, molecular docking, Prime MM/GBSA (molecular mechanics/generalized Born surface area) analysis, molecular dynamics (MD) simulation, and drug-likeness screening were performed to identify potential phytodrugs candidates for COVID-19 treatment. In support of these approaches, we used a series of computational modeling approaches to develop therapeutic agents against COVID-19. Out of the screened compounds against the selected SARS-CoV-2 therapeutic targets, only compounds with no violations of Lipinski's rule of five and high binding affinity were considered as potential anti-COVID-19 drugs. However, lonchocarpol A, diplacol, and broussonol E (lead compounds) were recorded as the best compounds that satisfied this requirement, and they demonstrated their highest binding affinity against 3CLpro. Therefore, the 3CLpro target and the three lead compounds were selected for further analysis. Through protein-ligand mapping and interaction profiling, the three lead compounds formed essential interactions such as hydrogen bonds and hydrophobic interactions with amino acid residues at the binding pocket of 3CLpro. The key amino acid residues at the 3CLpro active site participating in the hydrophobic and polar inter/intra molecular interaction were TYR54, PRO52, CYS44, MET49, MET165, CYS145, HIS41, THR26, THR25, GLN189, and THR190. The compounds demonstrated stable protein-ligand complexes in the active site of the target (3CLpro) over a 100 ns simulation period with stable protein-ligand trajectories. Drug-likeness screening shows that the compounds are druggable molecules, and the toxicity descriptors established that the compounds demonstrated a good biosafety profile. Furthermore, the compounds were chemically reactive with promising molecular electron potential properties. Collectively, we propose that the discovered lead compounds may open the way for establishing phytodrugs to manage COVID-19 pandemics and new chemical libraries to prevent COVID-19 entry into the host based on the findings of this computational investigation.

4.
Diagnostics (Basel) ; 12(9)2022 Aug 24.
Article in English | MEDLINE | ID: covidwho-1997542

ABSTRACT

Coronavirus disease 2019 (COVID-19) is primarily caused by various forms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants. COVID-19 is characterized by hyperinflammation, oxidative stress, multi-organ injury (MOI)-like acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Different biomarkers are used in the assessment of COVID-19 severity including D-dimer, ferritin, lactate dehydrogenase (LDH), and hypoxia-inducible factor (HIF). Interestingly, growth differentiation factor 15 (GDF15) has recently become a potential biomarker correlated with the COVID-19 severity. Thus, this critical review aimed to determine the critical association between GDF15 and COVID-19. The perfect function of GDF15 remains not well-recognized; nevertheless, it plays a vital role in controlling cell growth, apoptosis and inflammatory activation. Furthermore, GDF15 may act as anti-inflammatory and pro-inflammatory signaling in diverse cardiovascular complications. Furthermore, the release of GDF15 is activated by various growth factors and cytokines including macrophage colony-stimulating factor (M-CSF), angiotensin II (AngII) and p53. Therefore, higher expression of GDF15 in COVID-19 might a compensatory mechanism to stabilize and counteract dysregulated inflammatory reactions. In conclusion, GDF15 is an anti-inflammatory cytokine that could be associated with the COVID-19 severity. Increased GDF15 could be a compensatory mechanism against hyperinflammation and exaggerated immune response in the COVID-19. Experimental, preclinical and large-scale clinical studies are warranted in this regard.

5.
Biomedicines ; 10(8)2022 Aug 20.
Article in English | MEDLINE | ID: covidwho-1997513

ABSTRACT

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection can trigger the adaptive and innate immune responses, leading to uncontrolled inflammatory reactions and associated local and systematic tissue damage, along with thromboembolic disorders that may increase the risk of acute ischemic stroke (AIS) in COVID-19 patients. The neuropilin (NRP-1) which is a co-receptor for the vascular endothelial growth factor (VEGF), integrins, and plexins, is involved in the pathogenesis of AIS. NRP-1 is also regarded as a co-receptor for the entry of SARS-CoV-2 and facilitates its entry into the brain through the olfactory epithelium. NRP-1 is regarded as a cofactor for binding of SARS-CoV-2 with angiotensin-converting enzyme 2 (ACE2), since the absence of ACE2 reduces SARS-CoV-2 infectivity even in presence of NRP-1. Therefore, the aim of the present study was to clarify the potential role of NRP-1 in COVID-19 patients with AIS. SARS-CoV-2 may transmit to the brain through NRP-1 in the olfactory epithelium of the nasal cavity, leading to different neurological disorders, and therefore about 45% of COVID-19 patients had neurological manifestations. NRP-1 has the potential capability to attenuate neuroinflammation, blood-brain barrier (BBB) permeability, cerebral endothelial dysfunction (ED), and neuronal dysfunction that are uncommon in COVID-19 with neurological involvement, including AIS. Similarly, high NRP-1 serum level is linked with ED, oxidative stress, and the risk of pulmonary thrombosis in patients with severe COVID-19, suggesting a compensatory mechanism to overcome immuno-inflammatory disorders. In conclusion, NRP-1 has an important role in the pathogenesis of COVID-19 and AIS, and could be the potential biomarker linking the development of AIS in COVID-19. The present findings cannot provide a final conclusion, and thus in silico, experimental, in vitro, in vivo, preclinical, and clinical studies are recommended to confirm the potential role of NRP-1 in COVID-19, and to elucidate the pharmacological role of NRP-1 receptor agonists and antagonists in COVID-19.

7.
Biomedicines ; 10(8)2022 Jul 22.
Article in English | MEDLINE | ID: covidwho-1957221

ABSTRACT

Since its discovery in Wuhan, China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread over the world, having a huge impact on people's lives and health. The respiratory system is often targeted in people with the coronavirus disease 2019 (COVID-19). The virus can also infect many organs and tissues in the body, including the reproductive system. The consequences of the SARS-CoV-2 infection on fertility and pregnancy in hosts are poorly documented. Available data on other coronaviruses, such as severe acute respiratory syndrome (SARS-CoV) and Middle Eastern Respiratory Syndrome (MERS-CoV) coronaviruses, identified pregnant women as a vulnerable group with increased pregnancy-related complications. COVID-19 was also shown to impact pregnancy, which can be seen in either the mother or the fetus. Pregnant women more likely require COVID-19 intensive care treatment than non-pregnant women, and they are susceptible to giving birth prematurely and having their newborns admitted to the neonatal intensive care unit. Angiotensin converting enzyme 2 (ACE2), a key player of the ubiquitous renin-angiotensin system (RAS), is the principal host cellular receptor for SARS-CoV-2 spike protein. ACE2 is involved in the regulation of both male and female reproductive systems, suggesting that SARS-CoV-2 infection and associated RAS dysfunction could affect reproduction. Herein, we review the current knowledge about COVID-19 consequences on male and female fertility, pregnant women, and their fetuses. Furthermore, we describe the effects of COVID-19 vaccination on reproduction.

8.
Infect Disord Drug Targets ; 22(5): 47-57, 2022.
Article in English | MEDLINE | ID: covidwho-1951883

ABSTRACT

INTRODUCTION: SARS-CoV-2 is the novel coronavirus that causes severe acute respiratory syndrome and could afflict individuals from all walks of life. Children are usually asymptomatic or represent non-specific mild to moderate symptoms; therefore, they often remain undiagnosed and could be potential reservoirs and silent carriers of the virus. Despite the global attention to COVID-19 and its importance in public health, some clinical and paraclinical aspects of this disease in children are still unclear. Thus, we conducted a comprehensive systematic review of available literature to reflect on the current knowledge and practice of the disease among children. METHODS: This study was a systematic review of current evidence conducted in October 2020. We performed a systematic search using the keywords in online databases. The investigation adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to ensure the reliability and validity of extracted literature and results. RESULTS: We selected and reviewed 23 most related studies out of 1744 identified papers in an initial online search based on the inclusion and exclusion criteria of the present review; of whom 13 were original research studies, and 10 were letters to the editors, commentaries, viewpoints, consensus statements, and perspectives. Although due to the origin of the current pandemic, China was the country with the most publications (12 articles), data from several countries have been included in this review. CONCLUSION: COVID-19 can also affect children and cause systemic disease with several internal organ involvements. However, the prevalence, severity, and diversity of the symptoms in children are less than in adults. Cough and fever appear to be some of the most common symptoms, followed by other symptoms such as gastrointestinal manifestations. Comorbidities increase the risk of severe COVID-19 in children, and those without underlying conditions are very unlikely to suffer from severe disease. Mental health issues such as anxiety and depression due to the isolated situation caused by pandemics are common findings in children of early ages and should be seriously considered in current practice.


Subject(s)
COVID-19 , Adult , Child , Fever , Humans , Pandemics , Reproducibility of Results , SARS-CoV-2
9.
Molecules ; 27(12)2022 Jun 15.
Article in English | MEDLINE | ID: covidwho-1911483

ABSTRACT

We analyzed the epitope evolution of the spike protein in 1,860,489 SARS-CoV-2 genomes. The structural dynamics of these epitopes was determined by molecular modeling approaches. The D614G mutation, selected in the first months of the pandemic, is still present in currently circulating SARS-CoV-2 strains. This mutation facilitates the conformational change leading to the demasking of the ACE2 binding domain. D614G also abrogated the binding of facilitating antibodies to a linear epitope common to SARS-CoV-1 and SARS-CoV-2. The main neutralizing epitope of the N-terminal domain (NTD) of the spike protein showed extensive structural variability in SARS-CoV-2 variants, especially Delta and Omicron. This epitope is located on the flat surface of the NTD, a large electropositive area which binds to electronegatively charged lipid rafts of host cells. A facilitating epitope located on the lower part of the NTD appeared to be highly conserved among most SARS-CoV-2 variants, which may represent a risk of antibody-dependent enhancement (ADE). Overall, this retrospective analysis revealed an early divergence between conserved (facilitating) and variable (neutralizing) epitopes of the spike protein. These data aid in the designing of new antiviral strategies that could help to control COVID-19 infection by mimicking neutralizing antibodies or by blocking facilitating antibodies.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Antibodies, Neutralizing/genetics , COVID-19/genetics , Epitopes/genetics , Humans , Retrospective Studies , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
10.
Infect Disord Drug Targets ; 22(2): e230921196758, 2022.
Article in English | MEDLINE | ID: covidwho-1862463

ABSTRACT

INTRODUCTION: Many potential vaccines for COVID-19 are being studied and developed. Several studies have reported on the safety and efficacy of these vaccines. This systematic review aimed to report on the current evidence concerning the feasibility and effectiveness of vaccines for COVID-19. METHODS: A systematic search was carried out utilizing the keywords in the online databases, including Scopus, Web of Science, PubMed, Embase, and Cochrane. We included both human and non-human studies because of the vaccine novelty, limiting our ability to include sufficient human studies. RESULTS: This review showed several SARS-CoV-2 vaccines to be currently under development using different platforms, including eight vaccines that are adenovirus-based vectors, six vaccines that are RNA-based formulations, one vaccine being DNA-based formulation, and other vaccines using other platforms, including lipid nanoparticles. Although the safety and efficacy profiles of these vaccines are still under debate, some countries have allowed for emergency use of some vaccines in at-risk populations, such as healthcare workers and the elderly. CONCLUSION: It is crucial to gather as much clinically relevant evidence as possible regarding the immunogenicity, efficacy, and safety profiles of available vaccines and adhere wisely to CDC protocols and guidelines for vaccine production.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/prevention & control , COVID-19 Vaccines/classification , Feasibility Studies , Humans , Immunogenicity, Vaccine , Liposomes , Nanoparticles , SARS-CoV-2
11.
Molecules ; 27(9)2022 May 02.
Article in English | MEDLINE | ID: covidwho-1820343

ABSTRACT

COVID-19 has expanded across the world since its discovery in Wuhan (China) and has had a significant impact on people's lives and health. Long COVID is a term coined by the World Health Organization (WHO) to describe a variety of persistent symptoms after acute SARS-CoV-2 infection. Long COVID has been demonstrated to affect various SARS-CoV-2-infected persons, independently of the acute disease severity. The symptoms of long COVID, like acute COVID-19, consist in the set of damage to various organs and systems such as the respiratory, cardiovascular, neurological, endocrine, urinary, and immune systems. Fatigue, dyspnea, cardiac abnormalities, cognitive and attention impairments, sleep disturbances, post-traumatic stress disorder, muscle pain, concentration problems, and headache were all reported as symptoms of long COVID. At the molecular level, the renin-angiotensin system (RAS) is heavily involved in the pathogenesis of this illness, much as it is in the acute phase of the viral infection. In this review, we summarize the impact of long COVID on several organs and tissues, with a special focus on the significance of the RAS in the disease pathogenesis. Long COVID risk factors and potential therapy approaches are also explored.


Subject(s)
COVID-19 , Angiotensin-Converting Enzyme 2 , COVID-19/complications , Humans , Peptidyl-Dipeptidase A/metabolism , Renin-Angiotensin System/physiology , SARS-CoV-2
13.
Molecules ; 27(7):2048, 2022.
Article in English | MDPI | ID: covidwho-1762240

ABSTRACT

The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein to its cellular receptor, the angiotensin-converting enzyme 2 (ACE2), causes its downregulation, which subsequently leads to the dysregulation of the renin–angiotensin system (RAS) in favor of the ACE–angiotensin II (Ang II)–angiotensin II type I receptor (AT1R) axis. AT1R has a major role in RAS by being involved in several physiological events including blood pressure control and electrolyte balance. Following SARS-CoV-2 infection, pathogenic episodes generated by the vasoconstriction, proinflammatory, profibrotic, and prooxidative consequences of the Ang II–AT1R axis activation are accompanied by a hyperinflammatory state (cytokine storm) and an acute respiratory distress syndrome (ARDS). AT1R, a member of the G protein-coupled receptor (GPCR) family, modulates Ang II deleterious effects through the activation of multiple downstream signaling pathways, among which are MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases (PDGF, EGFR, insulin receptor), and nonreceptor tyrosine kinases (Src, JAK/STAT, focal adhesion kinase (FAK)), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. COVID-19 is well known for generating respiratory symptoms, but because ACE2 is expressed in various body tissues, several extrapulmonary pathologies are also manifested, including neurologic disorders, vasculature and myocardial complications, kidney injury, gastrointestinal symptoms, hepatic injury, hyperglycemia, and dermatologic complications. Therefore, the development of drugs based on RAS blockers, such as angiotensin II receptor blockers (ARBs), that inhibit the damaging axis of the RAS cascade may become one of the most promising approaches for the treatment of COVID-19 in the near future. We herein review the general features of AT1R, with a special focus on the receptor-mediated activation of the different downstream signaling pathways leading to specific cellular responses. In addition, we provide the latest insights into the roles of AT1R in COVID-19 outcomes in different systems of the human body, as well as the role of ARBs as tentative pharmacological agents to treat COVID-19.

14.
Health Sci Rep ; 5(2): e00516, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1701245

ABSTRACT

BACKGROUND AND AIMS: Scientists and healthcare workers have expressed their concerns on the impacts of the COVID-19 pandemic on vaccination coverage in children and adolescents. Therefore, we aimed to systematically review the studies addressing this issue worldwide. METHODS: We conducted a systematic search of relevant studies using the keywords on databases of PubMed, Web of Science, and Cochrane on May 22, 2021. The identified records were imported into EndNote software and underwent a two-phase screening process consisting of title/abstract and full-text screenings against inclusion criteria. The data of the included studies were summarized into a table and the findings were analyzed in a systematic approach. RESULTS: From 26 eligible studies, 21 studies demonstrated decreased vaccination rates in the children during the COVID-19 pandemic, while three studies found increased or no significant changes only in influenza vaccination. The two remaining studies from Brazil and Sweden also showed no significant changes in vaccination rates in the children during the pandemic. CONCLUSION: Most of the reports worldwide reported a decline or delay in vaccination at the time of the COVID-19 pandemic. A sustained catch-up program seems to be necessary, especially in low-income countries, to avoid any vaccine dose missing. Facilitating the vaccination process is recommended, such as decreasing the waiting time for vaccination at the health center, addressing the fear and concerns related to COVID infection for parents, and enhancing vaccine availability, and promoting access in remote areas. Countries should ensure proper vaccination to prevent future pandemics related to vaccine-preventable diseases.

15.
Immun Inflamm Dis ; 10(3): e580, 2022 03.
Article in English | MEDLINE | ID: covidwho-1568102

ABSTRACT

INTRODUCTION: Patients with COVID-19 may present different viral loads levels. However, the relationship between viral load and disease severity in COVID-19 is still unknown. Therefore, this study aimed to systematically review the association between SARS-CoV-2 viral load and COVID-19 severity. METHODS: The relevant studies using the keywords of "COVID-19" and "viral load" were searched in the databases of PubMed, Scopus, Google Scholar, and Web of Science. A two-step title/abstract screening process was carried out and the eligible studies were included in the study. RESULTS: Thirty-four studies were included from the initial 1015 records. The vast majority of studies have utilized real-time reverse transcription-polymerase chain reaction of the nasopharyngeal/respiratory swabs to report viral load. Viral loads were commonly reported either as cycle threshold (Ct ) or log10 RNA copies/ml. CONCLUSION: The results were inconclusive about the relationship between COVID-19 severity and viral load, as a similar number of studies either approved or opposed this hypothesis. However, the studies denote the direct relationship between older age and higher SARS-CoV-2 viral load, which is a known risk factor for COVID-19 mortality. The higher viral load in older patients may serve as a mechanism for any possible relationships between COVID-19 viral load and disease severity. There was a positive correlation between SARS-CoV-2 viral load and its transmissibility. Nonetheless, further studies are recommended to precisely characterize this matter.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Humans , Serologic Tests , Severity of Illness Index , Viral Load/methods
16.
Molecules ; 26(22)2021 Nov 17.
Article in English | MEDLINE | ID: covidwho-1524085

ABSTRACT

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), was first identified in Eastern Asia (Wuhan, China) in December 2019. The virus then spread to Europe and across all continents where it has led to higher mortality and morbidity, and was declared as a pandemic by the World Health Organization (WHO) in March 2020. Recently, different vaccines have been produced and seem to be more or less effective in protecting from COVID-19. The renin-angiotensin system (RAS), an essential enzymatic cascade involved in maintaining blood pressure and electrolyte balance, is involved in the pathogenicity of COVID-19, since the angiotensin-converting enzyme II (ACE2) acts as the cellular receptor for SARS-CoV-2 in many human tissues and organs. In fact, the viral entrance promotes a downregulation of ACE2 followed by RAS balance dysregulation and an overactivation of the angiotensin II (Ang II)-angiotensin II type I receptor (AT1R) axis, which is characterized by a strong vasoconstriction and the induction of the profibrotic, proapoptotic and proinflammatory signalizations in the lungs and other organs. This mechanism features a massive cytokine storm, hypercoagulation, an acute respiratory distress syndrome (ARDS) and subsequent multiple organ damage. While all individuals are vulnerable to SARS-CoV-2, the disease outcome and severity differ among people and countries and depend on a dual interaction between the virus and the affected host. Many studies have already pointed out the importance of host genetic polymorphisms (especially in the RAS) as well as other related factors such age, gender, lifestyle and habits and underlying pathologies or comorbidities (diabetes and cardiovascular diseases) that could render individuals at higher risk of infection and pathogenicity. In this review, we explore the correlation between all these risk factors as well as how and why they could account for severe post-COVID-19 complications.


Subject(s)
COVID-19/virology , Renin-Angiotensin System/genetics , SARS-CoV-2/physiology , COVID-19/genetics , Habits , Humans , Life Style , Polymorphism, Genetic , Sex Factors
18.
Virologie (Montrouge) ; 25(4): 213-223, 2021 08 01.
Article in French | MEDLINE | ID: covidwho-1381321

ABSTRACT

Epidemiological and observational studies converge to suspect today a risk of contracting Covid-19 around shared meals and drinks. Contamination of table objects (plates, cutlery, glasses) or food and beverages put in the mouth is possible through droplets projected during speech or through direct contacts by dirty hands. This contamination could involve employees in the food chain, restaurant or bar staff and diners among themselves. Biopersistence on hands and cold food supports the hypothesis of contamination by the food route. The oral-digestive route is also supported by the clinical presentation of the patients, the presence of ACE2 and TMPRSS2 receptors and the SARS-CoV-2 virus found in the entire digestive tract. In addition, the reproduction of the disease via the oral route in experimental animal models confirms this hypothesis. Prevention around the food chain and around the meal by strict hygiene measures, especially hand hygiene, is essential and may be extended to other fields of application of everyday life.


Subject(s)
COVID-19 , Animals , Humans , Hygiene , Meals , Restaurants , SARS-CoV-2
19.
Infect Disord Drug Targets ; 22(2): e270821195910, 2022.
Article in English | MEDLINE | ID: covidwho-1378162
20.
Front Nutr ; 8: 629440, 2021.
Article in English | MEDLINE | ID: covidwho-1332129

ABSTRACT

Coronavirus disease (COVID-19) is a global health challenge, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) triggers a plethora of respiratory disturbances and even multiple organs failure that can be fatal. Nutritional intervention is one of the key components toward to a proper management of COVID-19 patients, especially in those requiring medication, and should thus be considered the first-line treatment. Immuno-modulation and -stimulation are currently being explored in COVID-19 management and are gaining interest by food and pharmaceutical industries. Various dietary combinations, bioactive components, nutrients and fortified foods have been reported to modulate inflammation during disease progression. Dietary combinations of dairy-derived products and eggs are gaining an increasing attention given the huge immunomodulatory and anti-inflammatory properties attributed to some of their chemical constituents. Eggs are complex dietary components containing many essential nutrients and bioactive compounds as well as a high-quality proteins. Similarly, yogurts can replenish beneficial bacteria and contains macronutrients capable of stimulating immunity by enhancing cell immunity, reducing oxidative stress, neutralizing inflammation and regulating the intestinal barriers and gut microbiome. Thus, this review highlights the impact of nutritional intervention on COVID-19 management, focusing on the immunomodulatory and inflammatory effects of immune-enhancing nutrients.

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