Due to the large-scale spread of COVID-19,which has a significant impact on human health and social economy,developing effective antiviral drugs for COVID-19 is vital to saving human lives.Various biomedical associati...Due to the large-scale spread of COVID-19,which has a significant impact on human health and social economy,developing effective antiviral drugs for COVID-19 is vital to saving human lives.Various biomedical associations,e.g.,drug-virus and viral protein-host protein interactions,can be used for building biomedical knowledge graphs.Based on these sources,large-scale knowledge reasoning algorithms can be used to predict new links between antiviral drugs and viruses.To utilize the various heterogeneous biomedical associations,we proposed a fusion strategy to integrate the results of two tensor decomposition-based models(i.e.,CP-N3 and Compl Ex-N3).Sufficient experiments indicated that our method obtained high performance(MRR=0.2328).Compared with CP-N3,the mean reciprocal rank(MRR)is increased by 3.3%and compared with Compl Ex-N3,the MRR is increased by 3.5%.Meanwhile,we explored the relationship between the performance and relationship types,which indicated that there is a negative correlation(PCC=0.446,P-value=2.26 e-194)between the performance of triples predicted by our method and edge betweenness.展开更多
We performed density functional theory (DFT) calculations for ribonucleotides and active triphosphate metabolites of candidate drugs against Coronavirus disease 2019 (Covid-19). Frontier orbitals (highest occupied mol...We performed density functional theory (DFT) calculations for ribonucleotides and active triphosphate metabolites of candidate drugs against Coronavirus disease 2019 (Covid-19). Frontier orbitals (highest occupied molecular orbital and lowest unoccupied molecular</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">orbital) at optimized structure of each molecule were obtained. T-705RTP (active triphosphate metabolite of favipiravir) and cytidine triphosphate (CTP) have similar shapes of frontier orbitals. We also obtained similar shapes of frontier orbitals among dihydroxy GS-441524 triphosphate (GS-441524 is an active triphosphate metabolite of remdesivir) and adenosine triphosphate (ATP). From a theoretical </span><span style="font-family:Verdana;">viewpoint, we suggest T-705RTP is a CTP analogue and dihydroxy GS-441524</span><span style="font-family:Verdana;"> triphosphate is an</span></span><span style="font-family:""> </span><span style="font-family:Verdana;">ATP analogue.展开更多
Low-level laser therapy (LLLT) or cold laser has been used in medicine for several decades. However, the method utilizes a direct contact of the light beam with a patient. Further research resulted in development of a...Low-level laser therapy (LLLT) or cold laser has been used in medicine for several decades. However, the method utilizes a direct contact of the light beam with a patient. Further research resulted in development of another method that enables remote transmission of the pharmacological properties of a medicament into a human body with the application of low-level laser radiation as the light source. 18 patients with different viral diseases were treated with the antiviral drugs placed into the field formed by the unexplained properties of low-level laser radiation of the “device for transfer of the pharmacological properties of a drug into the patient’s body”. This resulted in improvement of the patient’s condition, the absence of side effects and adverse reactions when using drugs in the proposed device and shortened therapy period for patients with chronic hepatitis C infection and Covid-19 patients. The long-term follow-up of the patients with chronic hepatitis B infection showed that hepatitis B virus remained at low replication levels under the influence of the therapy, which made it possible to avoid such formidable complications of the disease as cirrhosis of the liver and liver cancer.展开更多
During the outbreak of the coronavirus disease 2019(COVID-19)pandemic,particular interest rose regarding the interaction between metabolic dysfunctionassociated fatty liver disease(MAFLD)and the COVID-19 infection.Sev...During the outbreak of the coronavirus disease 2019(COVID-19)pandemic,particular interest rose regarding the interaction between metabolic dysfunctionassociated fatty liver disease(MAFLD)and the COVID-19 infection.Several studies highlighted the fact that individuals with MAFLD had higher probability of severe acute respiratory syndrome coronavirus 2 infection and more severe adverse clinical outcomes.One of the proposed mechanisms is the inflammatory response pathway,especially the one involving cytokines,such as interleukin 6,which appeared particularly elevated in those patients and was deemed responsible for additional insult to the already damaged liver.This should increase our vigilance in terms of early detection,close follow up and early treatment for individuals with MAFLD and COVID-19 infection.In the direction of early diagnosis,biomarkers such as cytokeratin-18 and scoring systems such as Fibrosis-4 index score are proposed.COVID-19 is a newly described entity,expected to be of concern for the years to come,and MAFLD is a condition with an ever-increasing impact.Delineating the interaction between these two entities should be brought into the focus of research.Reducing morbidity and mortality of patients with COVID-19 and MAFLD should be the ultimate objective,and the optimal way to achieve this is by designing evidence-based prevention and treatment policies.展开更多
The world has been dealing with a novel severe acute respiratory syndrome(SARS-CoV-2)since the end of 2019,which threatens the lives of many peopleworldwide.COVID-19 causes respiratory infection with different symptom...The world has been dealing with a novel severe acute respiratory syndrome(SARS-CoV-2)since the end of 2019,which threatens the lives of many peopleworldwide.COVID-19 causes respiratory infection with different symptoms,from sneezing and coughing to pneumonia and sometimes gastric symptoms.Researchers worldwide are actively developing novel drug delivery systems(DDSs),such as stimuli-responsive DDSs.The ability of these carriers to respond to external/internal and even multiple stimuli is essential in creating“smart”DDS that can effectively control dosage,sustained release,individual variations,and targeted delivery.To conduct a comprehensive literature survey for this article,the terms“Stimuli-responsive”,“COVID-19”and“Drug delivery”were searched on databases/search engines like“Google Scholar”,“NCBI”,“PubMed”,and“Science Direct”.Many different types of DDSs have been proposed,including those responsive to various exogenous(light,heat,ultrasound andmagnetic field)or endogenous(microenvironmental changes in pH,ROS and enzymes)stimuli.Despite significant progress in DDS research,several challenging issues must be addressed to fill the gaps in the literature.Therefore,this study reviews the drug release mechanisms and applications of endogenous/exogenous stimuli-responsive DDSs while also exploring their potential with respect to COVID-19.展开更多
The goals of global vaccination are to control,eliminate,or eradicate infectious diseases in a sustainable way that strengthens public health systems.Although the use of vaccines is essential for the control of epidem...The goals of global vaccination are to control,eliminate,or eradicate infectious diseases in a sustainable way that strengthens public health systems.Although the use of vaccines is essential for the control of epidemics,the vaccines against coronavirus disease 2019(COVID-19)proved to be inadequate to end the pandemic and thus are considered incomplete.These vaccines failed to prevent infection,so their primary purpose has been shifted to prevent severe disease and reduce hospitalizations and deaths.Therefore,we believe that all the strategies available to reduce transmission,hospitalizations and deaths due to COVID-19 will be put in place.It is reported that uncontrolled inflammation and thrombosis are the principal mechanisms for aggravation and death in patients with COVID-19.Unlike corticosteroids that should not be administered at the beginning of the symptoms for their immunosuppressive action,which could worsen the evolution of the disease,the usefulness of non-steroidal anti-inflammatory drugs in the early at-home treatment of the disease is becoming evident.展开更多
Objective To study the feasibility of developing botanical drugs to treat intractable diseases and play an important role in dealing with major public health crises.Methods From January 1990 to May 2021,a bibliographi...Objective To study the feasibility of developing botanical drugs to treat intractable diseases and play an important role in dealing with major public health crises.Methods From January 1990 to May 2021,a bibliographic search was carried out on the use of botanical drugs,rare disease drugs,related registration management policies and regulations in PubMed and CNKI.The following keywords were searched in the database:Rare disease policies and regulations,orphan drugs,botanical drugs for intractable diseases,botanical drugs for the treatment of new coronary pneumonia,traditional Chinese medicine,and emergency guidelines for major public health crisis.Other data were obtained from“Chinese Pharmacopoeia”and relevant Chinese government websites for sorting and analysis.Results and Conclusion Based on 39 Chinese corresponding policies and regulations,challenges and opportunities of developing and researching drugs for treating rare diseases were found out after the analysis and comparison.Based on the study of national policies on drugs for rare diseases,the priority review and approval procedures in the drug registration,as well as China’s emergency guidelines and policies for major public health events,some problems in the use of drugs for rare diseases are found out.Therefore,it is recommended to actively adopt the property rights protection system,explore the folk prescriptions of traditional Chinese medicine and the potential of hospital preparations,and the registration review strategy of giving priority to the use of botanical drugs for rare diseases.Thus,the international status of botanical drugs for rare disease and the influence of responding to major public health events can be enhanced.展开更多
The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has caused a devastating health crisis worldwide.In this review,we have discussed that prop...The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has caused a devastating health crisis worldwide.In this review,we have discussed that prophylactic phytochemical quercetin supplementation in the form of foods or nutraceuticals may help manage the COVID-19 pandemic.The following evidence supports our argument.First,nuclear factor erythroid-derived 2-like 2(NRF2)agonists abrogate replication of SARS-CoV-2 in lung cells,and quercetin is a potent NRF2 agonist.Second,quercetin exerts antiviral activity against several zoonotic coronaviruses,including SARS-CoV-2,mainly by inhibiting the entry of virions into host cells.Third,inflammatory pathways activated by nuclear factor kappa B,inflammasome,and interleukin-6 signals elicit cytokine release syndrome that promotes acute respiratory distress syndrome in patients with COVID-19,and quercetin inhibits these pro-inflammatory signals.Fourth,patients with COVID-19 develop thrombosis,and quercetin mitigates coagulation abnormalities by inhibiting plasma protein disulfide isomerase.This review provides a strong rationale for testing quercetin for the management of COVID-19.展开更多
<strong>Background:</strong> SARS-CoV-2 (COVID-19) is a viral pandemic with no current vaccine or effective treatment. Hydroxychloroquine and azithromycin are not without cardiovascular risk or complicatio...<strong>Background:</strong> SARS-CoV-2 (COVID-19) is a viral pandemic with no current vaccine or effective treatment. Hydroxychloroquine and azithromycin are not without cardiovascular risk or complications, and these treatments can fail to aid in full recovery from COVID-19. As new treatments become approved for the pandemic, an inexpensive, non-toxic, and safe adjunctive therapy is needed. <strong>Case Presentation:</strong> A 59-year-old male presented with respiratory symptoms. Chest X-ray revealed classic indications of COVID-19 pneumonia. A PCR nasopharyngeal swab test confirmed a COVID-19 infection and hospital doctors prescribed Rocephin, azithromycin, and hydroxychloroquine. The patient was then prescribed Quercinex, a nebulized formula of quercetin-(cyclodextrin) (20 mg/mL) and N-acetylcysteine (100 mg/mL) three times daily for 14 days by physicians at Envita Medical Center for continued COVID-19 respiratory symptoms. Following 30 minutes after each nebulization treatment, the patient experienced immediate deep breathing relief that lasted for multiple hours. Within the following 48 hours after the first treatment, respiratory symptoms continued to diminish and resolve quickly. Finally, post-treatment follow-up chest X-rays revealed no pulmonary fibrosis (scarring) and clear lung fields. <strong>Conclusion: </strong>The Quercinex formula appeared to greatly alleviate the unresolved respiratory symptoms rapidly. Several mechanisms of the formula, namely antiviral and anti-inflammatory action, with direct administration via nebulizer to the deep lung tissue, could potentially explain the fast and complete recovery. We recommend that the Quercinex formula be considered for further clinical study as an adjuvant or on its own for COVID-19 and possibly other viral pulmonary conditions.展开更多
The global incidence of coronavirus disease 2019(COVID-19)continues to increase despite health care efforts.The disease is caused by coronavirus 2 with high transmission and mortality rates.Little is known about the m...The global incidence of coronavirus disease 2019(COVID-19)continues to increase despite health care efforts.The disease is caused by coronavirus 2 with high transmission and mortality rates.Little is known about the management of COVID-19 in advanced liver disease.The aim of work was to propose a plan for management of this drastic disease in case of this specific population with review of medications that could be suitable for advanced liver disease.All the guidelines and medications available for treatment of COVID-19 were reviewed with selection of the less toxic medications that could be used in advanced liver disease.Drugs suitable to manage COVID-19 in patients with liver disease might include remdesivir intravenously,nitazoxanide+sofosbuvir,ivermectin,tocilizumab,convalescent plasma,and low molecular weight heparin in certain situations.Advanced liver disease is associated with portal hypertension and splenomegaly with reduction of blood elements and immune dysfunction and impaired T cell function.Thus,when confronted by cytokine storm as an immune response to COVID-19,there may be an increase in the mortality rate of these patients.Through this review,a plan to treat COVID-19 in this special group of patients with advanced cirrhosis is proposed.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the pathogen of the ongoing coronavirus disease 2019(COVID-19)global pandemic.Here,by centralizing published cell-based experiments,clinical trials,and vir...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the pathogen of the ongoing coronavirus disease 2019(COVID-19)global pandemic.Here,by centralizing published cell-based experiments,clinical trials,and virtual drug screening data from the NCBI PubMed database,we developed a database of SARS-CoV-2 inhibitors for COVID-19,dbSCI,which includes 234 SARS-CoV-2 inhibitors collected from publications based on cell-based experiments,81 drugs of COVID-19 in clinical trials and 1305 potential SARS-CoV-2 inhibitors from bioinformatics analyses.dbSCI provides four major functions:(1)search the drug target or its inhibitor for SARS-CoV-2,(2)browse target/inhibitor information collected from cell experiments,clinical trials,and virtual drug screenings,(3)download,and(4)submit data.Each entry in dbSCI contains 18 types of information,including inhibitor/drug name,targeting protein,mechanism of inhibition,experimental technique,experimental sample type,and reference information.In summary,dbSCI provides a relatively comprehensive,credible repository for inhibitors/drugs against SARS-CoV-2 and their potential targeting mechanisms and it will be valuable for further studies to control COVID-19.展开更多
SARS-CoV-2 has been marked as a highly pathogenic coronavirus of COVID-19 disease into the human population,causing over 5.5 million confirmed cases worldwide.As COVID-19 has posed a global threat with significant hum...SARS-CoV-2 has been marked as a highly pathogenic coronavirus of COVID-19 disease into the human population,causing over 5.5 million confirmed cases worldwide.As COVID-19 has posed a global threat with significant human casualties and severe economic losses,there is a pressing demand to further understand the current situation and develop rational strategies to contain the drastic spread of the virus.Although there are no specific antiviral therapies that have proven effective in randomized clinical trials,currently,the rapid detection technology along with several promising therapeutics for COVID-19 have mitigated its drastic transmission.Besides,global institutions and corporations have commenced to parse out effective vaccines for the prevention of COVID-19.Herein,the present review will give exhaustive details of extensive researches concerning the drug discovery and therapeutic options for COVID-19 as well as some insightful discussions of the status of COVID-19.展开更多
BACKGROUND Hospitalized and severely ill coronavirus disease 2019(COVID-19)patients necessitate prophylactic or therapeutic anticoagulation to minimize the risk of thrombosis at different sites.Life-threatening bleedi...BACKGROUND Hospitalized and severely ill coronavirus disease 2019(COVID-19)patients necessitate prophylactic or therapeutic anticoagulation to minimize the risk of thrombosis at different sites.Life-threatening bleeding complications include spontaneous iliopsoas hematoma,peritoneal bleeding,and extra-abdominal manifestations such as intracranial hemorrhage.CASE SUMMARY Bleeding in the abdominal wall results in less severe complications than seen with iliopsoas hematoma or peritoneal bleeding.In our case series of 9 patients,we present retroperitoneal and abdominal bleeding complications following anticoagulation in hospitalized COVID-19 patients with severe acute respiratory syndrome coronavirus 2 pneumonia.Contrast-enhanced computed tomography(CE-CT)is the best imaging modality for assessing hematoma secondary to anticoagulation and determines the therapeutic approach,whether interventional,surgical,or conservative management.CONCLUSION We present the role of CE-CT for rapid and precise localization of the bleeding site and prognostic counseling.Finally,we provide a brief review of the literature.展开更多
Transgender persons constitute a non-negligible percentage of the general population.Physical gender-transitioning in trans persons is mainly achieved with hormonal cross-sex therapy and sex reassignment surgeries tha...Transgender persons constitute a non-negligible percentage of the general population.Physical gender-transitioning in trans persons is mainly achieved with hormonal cross-sex therapy and sex reassignment surgeries that aim to align bodily appearance with gender identity.Hormonal treatment acts via suppressing the secretion of the endogenous sex hormones and replacing them with the hormones of the desired sex.The administration of testosterone is the typical masculinizing treatment in trans men,whilst trans women are routinely treated with estradiol agents in combination with anti-androgens or gonadotrophinreleasing hormone agonists if testes are present.Exogenous androgenic steroids,estradiol agents,and anti-androgens have been implicated in a series of hepatotoxic effects.Thus,liver integrity is a major concern with the long-term administration of cross-sex therapy.Hepatic tissue is susceptible to coronavirus disease 19(COVID-19)through various pathophysiological mechanisms.Special consideration should be paid to minimize the risk of hepatic damage from the potential cumulative effect of COVID-19 and gender-affirming treatment in transgender patients.Appropriate care is significant,with continuous laboratory monitoring,clinical observation and,if needed,specific treatment,especially in severe cases of infection and in persons with additional liver pathologies.The pandemic can be an opportunity to provide equal access to care for all and increase the resilience of the transgender population.展开更多
This study investigated water samples collected from the surface water and groundwater in Wuhan City,Hubei Province,China in different stages of the outbreak of the coronavirus disease 2019(hereinafter referred to as ...This study investigated water samples collected from the surface water and groundwater in Wuhan City,Hubei Province,China in different stages of the outbreak of the coronavirus disease 2019(hereinafter referred to as COVID-19)in the city,aiming to determine the distribution characteristics of antiviral drugs in the city’s waters.The results are as follows.The main hydrochemical type of surface water and groundwater in Wuhan was Ca-HCO3.The major chemical components in the groundwater had higher concentrations and spatial variability than those in the surface water.Two antiviral drugs and two glucocorticoids were detected in the surface water,groundwater,and sewage during the COVID-19 outbreak.Among them,chloroquine phosphate and cortisone had higher detection rates of 32.26%and 25.80%,respectively in all samples.The concentrations of residual drugs in East Lake were higher than those in other waters.The main drug detected in the waters in the later stage of the COVID-19 outbreak in Wuhan was chloroquine phosphate,whose detection rates in the surface water and the groundwater were 53.85%and 28.57%,respectively.Moreover,the detection rate and concentration of chloroquine phosphate were higher in East Lake than in Huangjia Lake.The groundwater containing chloroquine phosphate was mainly distributed along the river areas where the groundwater was highly vulnerable.The residual drugs in the surface water and the groundwater had lower concentrations in the late stage of the COVID-19 outbreak than in the middle of the outbreak,and they have not yet caused any negative impacts on the ecological environment.展开更多
Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019(COVID...Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019(COVID-19)vaccination protocols.All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations,e.g.,BNT162b2,mRNA-1273,and ChAdOx1-S,can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration.Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination.The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies.Novel vaccine delivery platforms,e.g.,mRNA-containing lipid nanoparticles and adenoviral vectors,contribute to the inflammatory background that leads to an exaggerated immune response,while patterns of molecular mimicry between the spike(S)protein and prominent liver antigens may account for the autoimmune presentation.Immune mediators triggered by vaccination or vaccine ingredients per se,including autoreactive antibodies,cytokines,and cytotoxic T-cell populations,may inflict hepatocellular damage through wellestablished pathways.We aim to review available data associated with immunemediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.展开更多
Lately there has been a lot of interest worldwide in studies on the antiviral activities of marine natural secondary metabolites,notably marine polysaccharides.It has been established that polysaccharides made from ma...Lately there has been a lot of interest worldwide in studies on the antiviral activities of marine natural secondary metabolites,notably marine polysaccharides.It has been established that polysaccharides made from marine sources and their derivatives have antiviral effects against potent viruses.Agricultural,biological,food,and pharmaceutical industries all make extensive use of goods obtained from algae.The most well-known chemical components found in algae are polysaccharides,which have been the subject of a variety of studies because of their varied bioactivities.Polysaccharides made from algae have recently risen to the top of pharmaceutical research due to their fascinating antiviral potential.Currently,COVID-19 can be prevented with vaccination,but the brown alga Sargassum wightii has several bioactive compounds that have the following qualities and may be a better option.S.wightii is one of the marine algae species that is rich in sulfated polysaccharides,the secondary metabolites which have antiviral action and the capacity to prevent viral proliferation.Fucoidan,a long-chain sulfated polysaccharide found in various brown algae,has potent antiviral effects.Additionally,sulfated polysaccharides from green algae(such as ulvans)and red algae(such as carrageenan),and lectins from red algae(such as griffithsin)have antiviral therapeutic agents against coronaviruses and other viruses.This research focuses on screening seaweeds for possible antiviral compounds to treat viral infections notably COVID-19.展开更多
Introduction: Nursing students’ experiences during the pandemic provoked social isolation, the way to learn and every context increasing their stress and anxiety leading to drug use and abuse, among others. Problem-b...Introduction: Nursing students’ experiences during the pandemic provoked social isolation, the way to learn and every context increasing their stress and anxiety leading to drug use and abuse, among others. Problem-based learning (PBL) is a pedagogic strategy to strengthen significant learning;then the objective was to establish PBL influence in nursing students’ experiences on drug use and abuse during COVID-19 contingency. Methods: Qualitative, phenomenological and descriptive paradigm, 12 female and male nursing students aged 20 - 24 years old from the 5<sup>th</sup> and 6<sup>th</sup> semesters participated. Information collection was through semi-structured interview and a deep one in four cases. A guide of questions about: How the pandemic impacted your life? How did you face it? And what did you learn during this process? Those questions were used. Qualitative data analysis was based on De Souza Minayo, and signed informed consent was obtained from participants. Results: Students’ experiences allowed four categories to emerge, with six sub-categories. Category I. Students’ experiences on drug use and abuse facing the sanitary contingency;Category II. Students’ skills development to identify a problem and design of appropriate solutions;Category III. Developing skills to favor interpersonal relationships;Category IV. Influence of PBL in nursing students’ experiences on drug use and abuse during the COVID-19 contingency. Conclusion: PBL favored analysis and thoughts in nursing students’ experiences on drug use and abuse during the COVID-19 contingency, they worked collaboratively, developed resilience to daily life situations, and implemented stress coping strategies with their significant learning, which diminished their risk behavior.展开更多
There is a pressing need for effective therapeutics for coronavirus disease 2019(COVID-19),the respiratory disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The process of drug develop...There is a pressing need for effective therapeutics for coronavirus disease 2019(COVID-19),the respiratory disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The process of drug development is a costly and meticulously paced process,where progress is often hindered by the failure of initially promising leads.To aid this chal-lenge,in vitro human microphysiological systems need to be refined and adapted for mechanistic studies and drug screening,thereby saving valuable time and resources during a pandemic crisis.The SARS-CoV-2 virus attacks the lung,an organ where the unique three-dimensional(3D)structure of its functional units is critical for proper respiratory function.The in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between different cell types.Current model systems include Transwell,organoid and organ-on-a-chip or microphysiological systems(MPSs).We review models that have direct relevance toward modeling the pathology of COVID-19,including the processes of inflammation,edema,coagulation,as well as lung immune function.We also consider the practical issues that may influence the design and fabrication of MPS.The role of lung MPS is addressed in the context of multi-organ models,and it is discussed how high-throughput screening and artificial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.展开更多
基金partially supported by Beijing Natural Science Foundation(No.M21012)National Key Research and Development Program of China(No.2017YFC1703506,No.2018AAA0100302)National Natural Science Foundation of China(No.82174533)
文摘Due to the large-scale spread of COVID-19,which has a significant impact on human health and social economy,developing effective antiviral drugs for COVID-19 is vital to saving human lives.Various biomedical associations,e.g.,drug-virus and viral protein-host protein interactions,can be used for building biomedical knowledge graphs.Based on these sources,large-scale knowledge reasoning algorithms can be used to predict new links between antiviral drugs and viruses.To utilize the various heterogeneous biomedical associations,we proposed a fusion strategy to integrate the results of two tensor decomposition-based models(i.e.,CP-N3 and Compl Ex-N3).Sufficient experiments indicated that our method obtained high performance(MRR=0.2328).Compared with CP-N3,the mean reciprocal rank(MRR)is increased by 3.3%and compared with Compl Ex-N3,the MRR is increased by 3.5%.Meanwhile,we explored the relationship between the performance and relationship types,which indicated that there is a negative correlation(PCC=0.446,P-value=2.26 e-194)between the performance of triples predicted by our method and edge betweenness.
文摘We performed density functional theory (DFT) calculations for ribonucleotides and active triphosphate metabolites of candidate drugs against Coronavirus disease 2019 (Covid-19). Frontier orbitals (highest occupied molecular orbital and lowest unoccupied molecular</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">orbital) at optimized structure of each molecule were obtained. T-705RTP (active triphosphate metabolite of favipiravir) and cytidine triphosphate (CTP) have similar shapes of frontier orbitals. We also obtained similar shapes of frontier orbitals among dihydroxy GS-441524 triphosphate (GS-441524 is an active triphosphate metabolite of remdesivir) and adenosine triphosphate (ATP). From a theoretical </span><span style="font-family:Verdana;">viewpoint, we suggest T-705RTP is a CTP analogue and dihydroxy GS-441524</span><span style="font-family:Verdana;"> triphosphate is an</span></span><span style="font-family:""> </span><span style="font-family:Verdana;">ATP analogue.
文摘Low-level laser therapy (LLLT) or cold laser has been used in medicine for several decades. However, the method utilizes a direct contact of the light beam with a patient. Further research resulted in development of another method that enables remote transmission of the pharmacological properties of a medicament into a human body with the application of low-level laser radiation as the light source. 18 patients with different viral diseases were treated with the antiviral drugs placed into the field formed by the unexplained properties of low-level laser radiation of the “device for transfer of the pharmacological properties of a drug into the patient’s body”. This resulted in improvement of the patient’s condition, the absence of side effects and adverse reactions when using drugs in the proposed device and shortened therapy period for patients with chronic hepatitis C infection and Covid-19 patients. The long-term follow-up of the patients with chronic hepatitis B infection showed that hepatitis B virus remained at low replication levels under the influence of the therapy, which made it possible to avoid such formidable complications of the disease as cirrhosis of the liver and liver cancer.
文摘During the outbreak of the coronavirus disease 2019(COVID-19)pandemic,particular interest rose regarding the interaction between metabolic dysfunctionassociated fatty liver disease(MAFLD)and the COVID-19 infection.Several studies highlighted the fact that individuals with MAFLD had higher probability of severe acute respiratory syndrome coronavirus 2 infection and more severe adverse clinical outcomes.One of the proposed mechanisms is the inflammatory response pathway,especially the one involving cytokines,such as interleukin 6,which appeared particularly elevated in those patients and was deemed responsible for additional insult to the already damaged liver.This should increase our vigilance in terms of early detection,close follow up and early treatment for individuals with MAFLD and COVID-19 infection.In the direction of early diagnosis,biomarkers such as cytokeratin-18 and scoring systems such as Fibrosis-4 index score are proposed.COVID-19 is a newly described entity,expected to be of concern for the years to come,and MAFLD is a condition with an ever-increasing impact.Delineating the interaction between these two entities should be brought into the focus of research.Reducing morbidity and mortality of patients with COVID-19 and MAFLD should be the ultimate objective,and the optimal way to achieve this is by designing evidence-based prevention and treatment policies.
基金the financial support of Isfahan University of Medical Sciences by grant No.#199180.
文摘The world has been dealing with a novel severe acute respiratory syndrome(SARS-CoV-2)since the end of 2019,which threatens the lives of many peopleworldwide.COVID-19 causes respiratory infection with different symptoms,from sneezing and coughing to pneumonia and sometimes gastric symptoms.Researchers worldwide are actively developing novel drug delivery systems(DDSs),such as stimuli-responsive DDSs.The ability of these carriers to respond to external/internal and even multiple stimuli is essential in creating“smart”DDS that can effectively control dosage,sustained release,individual variations,and targeted delivery.To conduct a comprehensive literature survey for this article,the terms“Stimuli-responsive”,“COVID-19”and“Drug delivery”were searched on databases/search engines like“Google Scholar”,“NCBI”,“PubMed”,and“Science Direct”.Many different types of DDSs have been proposed,including those responsive to various exogenous(light,heat,ultrasound andmagnetic field)or endogenous(microenvironmental changes in pH,ROS and enzymes)stimuli.Despite significant progress in DDS research,several challenging issues must be addressed to fill the gaps in the literature.Therefore,this study reviews the drug release mechanisms and applications of endogenous/exogenous stimuli-responsive DDSs while also exploring their potential with respect to COVID-19.
文摘The goals of global vaccination are to control,eliminate,or eradicate infectious diseases in a sustainable way that strengthens public health systems.Although the use of vaccines is essential for the control of epidemics,the vaccines against coronavirus disease 2019(COVID-19)proved to be inadequate to end the pandemic and thus are considered incomplete.These vaccines failed to prevent infection,so their primary purpose has been shifted to prevent severe disease and reduce hospitalizations and deaths.Therefore,we believe that all the strategies available to reduce transmission,hospitalizations and deaths due to COVID-19 will be put in place.It is reported that uncontrolled inflammation and thrombosis are the principal mechanisms for aggravation and death in patients with COVID-19.Unlike corticosteroids that should not be administered at the beginning of the symptoms for their immunosuppressive action,which could worsen the evolution of the disease,the usefulness of non-steroidal anti-inflammatory drugs in the early at-home treatment of the disease is becoming evident.
文摘Objective To study the feasibility of developing botanical drugs to treat intractable diseases and play an important role in dealing with major public health crises.Methods From January 1990 to May 2021,a bibliographic search was carried out on the use of botanical drugs,rare disease drugs,related registration management policies and regulations in PubMed and CNKI.The following keywords were searched in the database:Rare disease policies and regulations,orphan drugs,botanical drugs for intractable diseases,botanical drugs for the treatment of new coronary pneumonia,traditional Chinese medicine,and emergency guidelines for major public health crisis.Other data were obtained from“Chinese Pharmacopoeia”and relevant Chinese government websites for sorting and analysis.Results and Conclusion Based on 39 Chinese corresponding policies and regulations,challenges and opportunities of developing and researching drugs for treating rare diseases were found out after the analysis and comparison.Based on the study of national policies on drugs for rare diseases,the priority review and approval procedures in the drug registration,as well as China’s emergency guidelines and policies for major public health events,some problems in the use of drugs for rare diseases are found out.Therefore,it is recommended to actively adopt the property rights protection system,explore the folk prescriptions of traditional Chinese medicine and the potential of hospital preparations,and the registration review strategy of giving priority to the use of botanical drugs for rare diseases.Thus,the international status of botanical drugs for rare disease and the influence of responding to major public health events can be enhanced.
基金the funding support from the Department of Biotechnology, Ramalingaswami Re-entry Fellowship (Grant No.: BT/RLF/Re-entry/37/2013)the Department of Science and Technology grant (Grant No.: DST/INT/SOUTH AFRICA/P13/2016)
文摘The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has caused a devastating health crisis worldwide.In this review,we have discussed that prophylactic phytochemical quercetin supplementation in the form of foods or nutraceuticals may help manage the COVID-19 pandemic.The following evidence supports our argument.First,nuclear factor erythroid-derived 2-like 2(NRF2)agonists abrogate replication of SARS-CoV-2 in lung cells,and quercetin is a potent NRF2 agonist.Second,quercetin exerts antiviral activity against several zoonotic coronaviruses,including SARS-CoV-2,mainly by inhibiting the entry of virions into host cells.Third,inflammatory pathways activated by nuclear factor kappa B,inflammasome,and interleukin-6 signals elicit cytokine release syndrome that promotes acute respiratory distress syndrome in patients with COVID-19,and quercetin inhibits these pro-inflammatory signals.Fourth,patients with COVID-19 develop thrombosis,and quercetin mitigates coagulation abnormalities by inhibiting plasma protein disulfide isomerase.This review provides a strong rationale for testing quercetin for the management of COVID-19.
文摘<strong>Background:</strong> SARS-CoV-2 (COVID-19) is a viral pandemic with no current vaccine or effective treatment. Hydroxychloroquine and azithromycin are not without cardiovascular risk or complications, and these treatments can fail to aid in full recovery from COVID-19. As new treatments become approved for the pandemic, an inexpensive, non-toxic, and safe adjunctive therapy is needed. <strong>Case Presentation:</strong> A 59-year-old male presented with respiratory symptoms. Chest X-ray revealed classic indications of COVID-19 pneumonia. A PCR nasopharyngeal swab test confirmed a COVID-19 infection and hospital doctors prescribed Rocephin, azithromycin, and hydroxychloroquine. The patient was then prescribed Quercinex, a nebulized formula of quercetin-(cyclodextrin) (20 mg/mL) and N-acetylcysteine (100 mg/mL) three times daily for 14 days by physicians at Envita Medical Center for continued COVID-19 respiratory symptoms. Following 30 minutes after each nebulization treatment, the patient experienced immediate deep breathing relief that lasted for multiple hours. Within the following 48 hours after the first treatment, respiratory symptoms continued to diminish and resolve quickly. Finally, post-treatment follow-up chest X-rays revealed no pulmonary fibrosis (scarring) and clear lung fields. <strong>Conclusion: </strong>The Quercinex formula appeared to greatly alleviate the unresolved respiratory symptoms rapidly. Several mechanisms of the formula, namely antiviral and anti-inflammatory action, with direct administration via nebulizer to the deep lung tissue, could potentially explain the fast and complete recovery. We recommend that the Quercinex formula be considered for further clinical study as an adjuvant or on its own for COVID-19 and possibly other viral pulmonary conditions.
文摘The global incidence of coronavirus disease 2019(COVID-19)continues to increase despite health care efforts.The disease is caused by coronavirus 2 with high transmission and mortality rates.Little is known about the management of COVID-19 in advanced liver disease.The aim of work was to propose a plan for management of this drastic disease in case of this specific population with review of medications that could be suitable for advanced liver disease.All the guidelines and medications available for treatment of COVID-19 were reviewed with selection of the less toxic medications that could be used in advanced liver disease.Drugs suitable to manage COVID-19 in patients with liver disease might include remdesivir intravenously,nitazoxanide+sofosbuvir,ivermectin,tocilizumab,convalescent plasma,and low molecular weight heparin in certain situations.Advanced liver disease is associated with portal hypertension and splenomegaly with reduction of blood elements and immune dysfunction and impaired T cell function.Thus,when confronted by cytokine storm as an immune response to COVID-19,there may be an increase in the mortality rate of these patients.Through this review,a plan to treat COVID-19 in this special group of patients with advanced cirrhosis is proposed.
基金supported by the Innovation and Entrepreneurship Training Program for College Students in Henan University(20221022009)the Key Scientific Research Project of Henan Province(22A310012)+1 种基金supporting program for Central Plain Young Top Talents(ZYQR201912176)the program from Academy for Advanced Interdisciplinary Studies of Henan University(Y21008L).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the pathogen of the ongoing coronavirus disease 2019(COVID-19)global pandemic.Here,by centralizing published cell-based experiments,clinical trials,and virtual drug screening data from the NCBI PubMed database,we developed a database of SARS-CoV-2 inhibitors for COVID-19,dbSCI,which includes 234 SARS-CoV-2 inhibitors collected from publications based on cell-based experiments,81 drugs of COVID-19 in clinical trials and 1305 potential SARS-CoV-2 inhibitors from bioinformatics analyses.dbSCI provides four major functions:(1)search the drug target or its inhibitor for SARS-CoV-2,(2)browse target/inhibitor information collected from cell experiments,clinical trials,and virtual drug screenings,(3)download,and(4)submit data.Each entry in dbSCI contains 18 types of information,including inhibitor/drug name,targeting protein,mechanism of inhibition,experimental technique,experimental sample type,and reference information.In summary,dbSCI provides a relatively comprehensive,credible repository for inhibitors/drugs against SARS-CoV-2 and their potential targeting mechanisms and it will be valuable for further studies to control COVID-19.
文摘SARS-CoV-2 has been marked as a highly pathogenic coronavirus of COVID-19 disease into the human population,causing over 5.5 million confirmed cases worldwide.As COVID-19 has posed a global threat with significant human casualties and severe economic losses,there is a pressing demand to further understand the current situation and develop rational strategies to contain the drastic spread of the virus.Although there are no specific antiviral therapies that have proven effective in randomized clinical trials,currently,the rapid detection technology along with several promising therapeutics for COVID-19 have mitigated its drastic transmission.Besides,global institutions and corporations have commenced to parse out effective vaccines for the prevention of COVID-19.Herein,the present review will give exhaustive details of extensive researches concerning the drug discovery and therapeutic options for COVID-19 as well as some insightful discussions of the status of COVID-19.
文摘BACKGROUND Hospitalized and severely ill coronavirus disease 2019(COVID-19)patients necessitate prophylactic or therapeutic anticoagulation to minimize the risk of thrombosis at different sites.Life-threatening bleeding complications include spontaneous iliopsoas hematoma,peritoneal bleeding,and extra-abdominal manifestations such as intracranial hemorrhage.CASE SUMMARY Bleeding in the abdominal wall results in less severe complications than seen with iliopsoas hematoma or peritoneal bleeding.In our case series of 9 patients,we present retroperitoneal and abdominal bleeding complications following anticoagulation in hospitalized COVID-19 patients with severe acute respiratory syndrome coronavirus 2 pneumonia.Contrast-enhanced computed tomography(CE-CT)is the best imaging modality for assessing hematoma secondary to anticoagulation and determines the therapeutic approach,whether interventional,surgical,or conservative management.CONCLUSION We present the role of CE-CT for rapid and precise localization of the bleeding site and prognostic counseling.Finally,we provide a brief review of the literature.
文摘Transgender persons constitute a non-negligible percentage of the general population.Physical gender-transitioning in trans persons is mainly achieved with hormonal cross-sex therapy and sex reassignment surgeries that aim to align bodily appearance with gender identity.Hormonal treatment acts via suppressing the secretion of the endogenous sex hormones and replacing them with the hormones of the desired sex.The administration of testosterone is the typical masculinizing treatment in trans men,whilst trans women are routinely treated with estradiol agents in combination with anti-androgens or gonadotrophinreleasing hormone agonists if testes are present.Exogenous androgenic steroids,estradiol agents,and anti-androgens have been implicated in a series of hepatotoxic effects.Thus,liver integrity is a major concern with the long-term administration of cross-sex therapy.Hepatic tissue is susceptible to coronavirus disease 19(COVID-19)through various pathophysiological mechanisms.Special consideration should be paid to minimize the risk of hepatic damage from the potential cumulative effect of COVID-19 and gender-affirming treatment in transgender patients.Appropriate care is significant,with continuous laboratory monitoring,clinical observation and,if needed,specific treatment,especially in severe cases of infection and in persons with additional liver pathologies.The pandemic can be an opportunity to provide equal access to care for all and increase the resilience of the transgender population.
基金This research was jointly by the China Geological Survey Project Multi-Factor Urban Geological Survey of Wuhan(DD20190282)Survey and Evaluation of Riverside Urban Geological Safety in Wuhan(DD20221734).
文摘This study investigated water samples collected from the surface water and groundwater in Wuhan City,Hubei Province,China in different stages of the outbreak of the coronavirus disease 2019(hereinafter referred to as COVID-19)in the city,aiming to determine the distribution characteristics of antiviral drugs in the city’s waters.The results are as follows.The main hydrochemical type of surface water and groundwater in Wuhan was Ca-HCO3.The major chemical components in the groundwater had higher concentrations and spatial variability than those in the surface water.Two antiviral drugs and two glucocorticoids were detected in the surface water,groundwater,and sewage during the COVID-19 outbreak.Among them,chloroquine phosphate and cortisone had higher detection rates of 32.26%and 25.80%,respectively in all samples.The concentrations of residual drugs in East Lake were higher than those in other waters.The main drug detected in the waters in the later stage of the COVID-19 outbreak in Wuhan was chloroquine phosphate,whose detection rates in the surface water and the groundwater were 53.85%and 28.57%,respectively.Moreover,the detection rate and concentration of chloroquine phosphate were higher in East Lake than in Huangjia Lake.The groundwater containing chloroquine phosphate was mainly distributed along the river areas where the groundwater was highly vulnerable.The residual drugs in the surface water and the groundwater had lower concentrations in the late stage of the COVID-19 outbreak than in the middle of the outbreak,and they have not yet caused any negative impacts on the ecological environment.
文摘Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019(COVID-19)vaccination protocols.All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations,e.g.,BNT162b2,mRNA-1273,and ChAdOx1-S,can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration.Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination.The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies.Novel vaccine delivery platforms,e.g.,mRNA-containing lipid nanoparticles and adenoviral vectors,contribute to the inflammatory background that leads to an exaggerated immune response,while patterns of molecular mimicry between the spike(S)protein and prominent liver antigens may account for the autoimmune presentation.Immune mediators triggered by vaccination or vaccine ingredients per se,including autoreactive antibodies,cytokines,and cytotoxic T-cell populations,may inflict hepatocellular damage through wellestablished pathways.We aim to review available data associated with immunemediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.
文摘Lately there has been a lot of interest worldwide in studies on the antiviral activities of marine natural secondary metabolites,notably marine polysaccharides.It has been established that polysaccharides made from marine sources and their derivatives have antiviral effects against potent viruses.Agricultural,biological,food,and pharmaceutical industries all make extensive use of goods obtained from algae.The most well-known chemical components found in algae are polysaccharides,which have been the subject of a variety of studies because of their varied bioactivities.Polysaccharides made from algae have recently risen to the top of pharmaceutical research due to their fascinating antiviral potential.Currently,COVID-19 can be prevented with vaccination,but the brown alga Sargassum wightii has several bioactive compounds that have the following qualities and may be a better option.S.wightii is one of the marine algae species that is rich in sulfated polysaccharides,the secondary metabolites which have antiviral action and the capacity to prevent viral proliferation.Fucoidan,a long-chain sulfated polysaccharide found in various brown algae,has potent antiviral effects.Additionally,sulfated polysaccharides from green algae(such as ulvans)and red algae(such as carrageenan),and lectins from red algae(such as griffithsin)have antiviral therapeutic agents against coronaviruses and other viruses.This research focuses on screening seaweeds for possible antiviral compounds to treat viral infections notably COVID-19.
文摘Introduction: Nursing students’ experiences during the pandemic provoked social isolation, the way to learn and every context increasing their stress and anxiety leading to drug use and abuse, among others. Problem-based learning (PBL) is a pedagogic strategy to strengthen significant learning;then the objective was to establish PBL influence in nursing students’ experiences on drug use and abuse during COVID-19 contingency. Methods: Qualitative, phenomenological and descriptive paradigm, 12 female and male nursing students aged 20 - 24 years old from the 5<sup>th</sup> and 6<sup>th</sup> semesters participated. Information collection was through semi-structured interview and a deep one in four cases. A guide of questions about: How the pandemic impacted your life? How did you face it? And what did you learn during this process? Those questions were used. Qualitative data analysis was based on De Souza Minayo, and signed informed consent was obtained from participants. Results: Students’ experiences allowed four categories to emerge, with six sub-categories. Category I. Students’ experiences on drug use and abuse facing the sanitary contingency;Category II. Students’ skills development to identify a problem and design of appropriate solutions;Category III. Developing skills to favor interpersonal relationships;Category IV. Influence of PBL in nursing students’ experiences on drug use and abuse during the COVID-19 contingency. Conclusion: PBL favored analysis and thoughts in nursing students’ experiences on drug use and abuse during the COVID-19 contingency, they worked collaboratively, developed resilience to daily life situations, and implemented stress coping strategies with their significant learning, which diminished their risk behavior.
基金funding from National Institutes of Health(No.1UG3TR003148-01)the American Heart Association(No.442611-NU-80922)+1 种基金California Institute for Regenerative Medicine(No.DISC2COVID19-11838)COVID-19 research funding from David Geffen School of Medicine at UCLA.
文摘There is a pressing need for effective therapeutics for coronavirus disease 2019(COVID-19),the respiratory disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The process of drug development is a costly and meticulously paced process,where progress is often hindered by the failure of initially promising leads.To aid this chal-lenge,in vitro human microphysiological systems need to be refined and adapted for mechanistic studies and drug screening,thereby saving valuable time and resources during a pandemic crisis.The SARS-CoV-2 virus attacks the lung,an organ where the unique three-dimensional(3D)structure of its functional units is critical for proper respiratory function.The in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between different cell types.Current model systems include Transwell,organoid and organ-on-a-chip or microphysiological systems(MPSs).We review models that have direct relevance toward modeling the pathology of COVID-19,including the processes of inflammation,edema,coagulation,as well as lung immune function.We also consider the practical issues that may influence the design and fabrication of MPS.The role of lung MPS is addressed in the context of multi-organ models,and it is discussed how high-throughput screening and artificial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.