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1.
Human Gene Therapy Methods ; 33(23-24):A186-A187, 2022.
Article in English | EMBASE | ID: covidwho-2188086

ABSTRACT

Human adenoviruses are phylogenetically divided across seven species, A-G, causing transient mild illnesses, except in immunocompromised individuals. Their double stranded DNA genome is amenable to genetic manipulations, enabling development of highly engineered virotherapies. Species D adenoviruses have naturally low seroprevalence rates, an important trait in avoiding neutralising anti-vector immunity. We previously demonstrated that HAdV-D26, the platform of the Janssen SARS-CoV2 vaccine, uses sialic acid as a primary cell entry receptor. Here, we structurally and biologically investigated sialic acid usage across species D. We solved multiple structures of species D adenovirus fiber knob proteins alone and in complex with sialic acid, identifying a conserved binding pocket common with known sialic acid binders HAdV-D26 and 37. Using fiber-knob pseudotyped viruses, we demonstrate significantly reduced transduction in cells treated with neuraminidase to remove sialic acid residues in HAdV-D26 and 53, with HAdV-D15, 24 and 29 also demonstrating non-significant reductions. IC50 data also showed highlighted binding to CAR, although at a significantly lower affinity compared to the CAR-binding HAdV-C5. Improved understanding of the usage of sialic acid as a receptor will enable better exploitation of the species D adenoviruses as therapeutic vectors. Our findings raise the possibility of a conserved sialic acid binding pocket within species D adenoviruses resulting in varying affinity levels. Further evaluation of specific glycan binding patterns used by these viruses, as observed between HAdV-D37 and GD1a glycan, will better inform the design of appropriate antivirals to contain adenovirus outbreaks as well as the engineering of targeted vectors for translational applications.

2.
Hematology, Transfusion and Cell Therapy ; 44(Supplement 2):S657-S658, 2022.
Article in English | EMBASE | ID: covidwho-2179212

ABSTRACT

Objetivos: A COVID-19 apresenta alta taxa de infectividade e um amplo espectro clinico no qual, aproximadamente 3%-20% dos infectados necessitam de internacao hospitalar sendo destes, 10%-30% cuidados intensivos. A forma grave parece estar associada a um descontrole da resposta imune do hospedeiro, desta forma, a caracterizacao do perfil imune e fundamental para a definicao prognostica e terapeutica. Materiais e Metodos: Estudo prospectivo realizado de maio de 2020 a maio de 2021, recrutou adultos com COVID-19 grave internados em UTI, para a avaliacao de 17 citocinas. Foram realizadas coletas laboratoriais na admissao na UTI (D0) e apos, a cada 4 dias por no maximo, 20 dias. O grupo controle incluiu doadores de sangue voluntarios. O desfecho primario avaliado foi a sobrevida livre de Ventilacao Mecanica (VM). Este projeto foi aprovado pelo Comite de etica. Resultados: Nos 62 pacientes avaliados a idade mediana foi de 58,7 anos, houve uma predominancia no sexo masculino (74.2%), e alta prevalencia de comorbidades. A taxa de mortalidade foi de 8%, sendo 55% a necessidade de suporte ventilatorio invasivo. Dentre as citocinas avaliadas, se destacaram os niveis sericos elevados de Granzima B, Perforina e sFAS (FAS soluvel) nos doentes em relacao aos controles. Os valores medianos de Granzima B no D0 foram maiores quanto menor o tempo de sintomas. A avaliacao no D0 atraves da curva ROC, demonstrou um papel preditivo nos niveis de Perforina, Granzima B e sFAS para a evolucao para VM. Nao obstante, os niveis de sFAS no decorrer da internacao apresentaram correlacao direta com pior desfecho sendo um potencial marcador prognostico. Discussao: A apoptose ocorre atraves de 3 mecanismos: mediada por granulos (granzimas e perforinas);citotoxicidade atraves de Fas-FasL;e citotoxicidade atraves do ligante TRAIL. Maucourant et al. documentaram no diagnostico de COVID-19 grave, o aumento nos niveis de Perforina, representando a resposta celular NK. Alem disso, foi descrito que no decorrer da infeccao ha uma reducao da citotoxicidade NK, decorrente da exaustao imune. Em nossa amostra, os niveis no D0 destas 2 moleculas se relacionaram a gravidade, alem disso, foi possivel observar o aumento de Granzima B relacionado a precocidade dos sintomas, desta forma, indicando uma reducao evolutiva. O receptor FAS e seu Ligante (FASL), integrantes da familia TNF, sao responsaveis pela apoptose das celulas infectadas no inicio da infeccao e, mais tardio, dos linfocitos maduros auto-reativos. As formas soluveis dos receptores regulam de forma competitiva as suas particulas de membrana (inibicao). No entanto, sFAS e sFASL parecem ter papeis diferentes conforme a patologia e o momento da infeccao, podendo inibir seus receptores transmembrana ou desenvolver funcoes analogas. Andre et al. encontraram uma relacao direta dos niveis de sFASL no COVID-19 grave com Fas-FasL linfocitarios, a linfopenia e o pior prognostico. Sendo responsaveis, portanto, pela apoptose de linfocitos T ativados. Diante disso, avaliaram o uso de um inibidor de caspase-1 para bloquear o Fas, o qual aumentou a resposta antiviral. Conclusao: O sFAS e um potencial biomarcador para a avaliacao preditiva prognostica, desta forma, nossos dados sugerem que as vias da apoptose devem ser estudadas a fim de confirmar estes dados e ainda, explorar seu potencial como alvo terapeutico. Copyright © 2022

3.
Journal of Pharmaceutical Negative Results ; 13:6206-6211, 2022.
Article in English | EMBASE | ID: covidwho-2206804

ABSTRACT

Combating the spread and deaths brought on by the new corona virus is a big challenge for the world today (COVID-19). The economic and medical costs of this infectious disease on the human population are enormous. Around the world, COVID-19 had a negative impact on education. There hasn't been a clear cure or vaccine recommended for COVID-19 as of yet. Different antiviral drug combinations are used by doctors. Additionally, plasma treatment is used. The only method to protect oneself is to keep a distance from others, practise good hygiene, and wear a mask. The use of nanotechnology can be particularly effective in the fight against COVID-19. Nanomedicine can make use of nanoparticles. For added protection, it can be coated or sprayed on a mask or PPE kit. It has also been used to identify Covid 19 patients early. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

4.
Journal of Pharmaceutical Negative Results ; 13:2802-2805, 2022.
Article in English | EMBASE | ID: covidwho-2206713

ABSTRACT

COVID-19 is a pandemic viral infection that caused a hesitated health state for all countries worldwide;being a healthcare professional puts you in crucial responsibilities and drive to be more aware and efficient in managing and controlling this pandemic;the pharmacist has a great role in preventing the COVID-19 from dissemination and providing all healthcare services such as drugs, vaccines, sterilized materials, and sterilization techniques for all healthcare settings, the pharmacist has an essential step in raising the degree of COVID-19 eradication in all countries, in this review, a collection of many articles were reviewed, discussed to conclude that the pharmacist is one of the biggest healthcare professionals. They are working continuously to control this COVID-19 pandemic. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

5.
Anesteziologie a Intenzivni Medicina ; 31(3):119-123, 2020.
Article in Czech | EMBASE | ID: covidwho-2206295

ABSTRACT

During the epidemic of COVID-19, there often arises an urgent need for the so-called off-label use of medicinal products, i.e. use of a medicinal product that is not in accordance with its Summary of Product Characteristics (SPC). Most often, a medicinal product registered for a different indication is used. The goal of this paper is to provide the reader with an analysis of legal conditions under which the off-label use of medicinal products in COVID-19 patients is legally safe. If the provider of health services fulfils these conditions, they will not be held liable for immaterial harm that could potentially occur to the patient. Copyright © 2020, Czech Medical Association J.E. Purkyne. All rights reserved.

6.
Acta Haematologica Polonica ; 53(5):301-302, 2022.
Article in English | EMBASE | ID: covidwho-2155686
7.
Pharmaceutical Journal ; 309(7966), 2022.
Article in English | EMBASE | ID: covidwho-2154185
8.
Medical Journal of Malaysia ; 77(Supplement 4):51, 2022.
Article in English | EMBASE | ID: covidwho-2147611

ABSTRACT

Introduction: The novel Coronavirus, SARS-CoV-2 causing the COVID-19 pandemic has become a serious public health issue worldwide. This has created a huge demand for discovering antiviral drugs for treating COVID-19. Phytocompounds especially terpenoids have potential for effective antiviral activities against SARS-CoV-2. In this study, a library of terpenoid compounds was screened for their interactions with protein targets of SARS-CoV-2 using the computational docking approach. Material(s) and Method(s): Terpenoid compounds were retrieved from data bases such as PubChem (NCBI, USA), Naturally-occurring Plantbased Anti-cancer Compound-activity Target (NPACT) and Kyoto Encyclopaedia for Gene and Genome (KEGG). Docking of terpenoid compounds with the main protease (Mpro) and RNA-dependent RNA-polymerase (RdRP) was performed using Autodock Vina. Drug-likeness properties were predicted using SwissADME web tool. Result(s) and Conclusion(s): Out of 850 terpenoid compounds docked with SARS-CoV-2 protein targets, Agavoside A showed the highest interaction energy value of - 9.1kcal/mol against Mpro and formed hydrogen bond (HB) interactions with Lys137, Asp197, Thr199 and Leu287. Labriformidin and Absinthin showed interaction energy values of -9 and -8.8kcal/mol, respectively, with Mpro. Against RdRp, Absinthin showed the highest interaction energy value of -9.9 kcal/mol and formed HB interactions with Asp760, Asp623 and Cys622. Agavoside A and Labriformidin showed interaction energy values of -9.6 and -9.4kcal/mol, respectively, with RdRp. ADMET analysis revealed that all three compounds possess non-toxic and non-carcinogenic properties. The lead terpenoid compounds Agavoside A, Labriformidin, and Absinthin could be potential antiviral agents for treating COVID-19. However, further in-vitro and in-vivo studies are required.

9.
Journal of Experimental and Clinical Medicine (Turkey) ; 39(4):1255-1269, 2022.
Article in English | EMBASE | ID: covidwho-2146844

ABSTRACT

While the COVID-19 pandemic is expanding at an alarming rate, there is currently no treatment option for this disease. Therefore, it is necessary to find an effective treatment special for hospitalized COVID-19 patients at the earliest possible time. One of the promising options which should be investigated is the possible effects of old drugs or drug repositioning. This strategy has less risk with more economic advantages and can benefit the long-term control of this pandemic. Our study aimed to give an overview, update the current status of drug candidates (both virus-targeting and host-targeting drugs) for repurposing in COVID-19 infection, and assess the possible mechanism of their effect, in vivo antiviral efficacy, and clinical studies. Copyright © 2022 Ondokuz Mayis Universitesi. All rights reserved.

10.
Deutsches Arzteblatt International ; 119(39):A1638-A1640, 2022.
Article in German | EMBASE | ID: covidwho-2125114
11.
Medicine Today ; 23(11):41-47, 2022.
Article in English | EMBASE | ID: covidwho-2124633

ABSTRACT

With the rapid introduction of new treatments for mild COVID-19, GPs need to be aware of the latest information to help them recognise which patients are candidates for available therapies. Treatment options for suitable patients with mild COVID-19 include antivirals and monoclonal antibodies, with the oral antivirals being most relevant for GPs. GPs should always refer to COVID-19 living guidelines to ensure they provide accurate advice to their patients. Copyright © MedicineToday 2022.

12.
Pakistan Journal of Medical and Health Sciences ; 16(8):24-26, 2022.
Article in English | EMBASE | ID: covidwho-2067738

ABSTRACT

Aim: To evaluate the potential use of ivermectin with standard therapy among mild to moderate covid-19 illness. Methods: This is a single-centered, prospective observational, randomized, parallel group (1:1 ratio), standard versus controlled ivermectin study recruited 210 confirmed COVID-19 positive patients who were admitted in COVID treatment center of Dr Ruth Kum Pafu Civil hospital Karachi, Pakistan from 1st November 2020 to 30th May 2021. Data were analyzed using SPSS version Results: Total of 210 patients were enrolled in the study and aged matched patients were divided in two groups 105 patients received ivermectin 6 mg twice a day for five days along with standard therapy while remaining 105 patients received standard therapy as per local and international guidelines. Male were 140(66.7%) and female 70(33.3%);age ranges between 26 to 77 years and majority 140( 66.7%) were more than 50 years of age. Fever, dry cough and dyspnea were the major symptoms seen;112(53.3%) patients had DM as a comorbid illness . Total of 21(20%) of 105 patients of ivermectin group had negative PCR for COVID 19 on day seven while the other group had positive covid test in all of 105 patients . On day 10 total of 49 more patients from ivermectin group found COVID negative along with 21 previously negative had second PCR was found negative in this way total of 70( 66.7%) of ivermectin group had negative PCR for COVID 19 while 21(20%) patients from non ivermectin got negative PCR for COVID 19 on day 10 . Conclusion: Use of ivermectin with standard therapy clear the virus earlier than standard therapy in mild to moderate COVID-19 infected patients admitted in COVID treatment center of Dr Ruth Kum Pafu Civil Hospital Karachi.

13.
NeuroQuantology ; 20(10):7528-7533, 2022.
Article in English | EMBASE | ID: covidwho-2067316

ABSTRACT

Background: The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China and spread around the world. Genomic analysis revealed that SARS-CoV-2 is phylogenetically related to severe acute respiratory syndrome-like (SARS-like) bat viruses, therefore bats could be the possible primary reservoir.The intermediate source of origin and transfer to humans is not known, however, the rapid human to human transfer has been confirmed widely. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. However, few broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery.The liver, the largest internal organ in the body, is essential in keeping the body functioning properly. It removes or neutralizes poisons from the blood, produces immune agents to control infection, and removes germs and bacteria from the blood. It makes proteins that regulate blood clotting and produces bile to help absorb fats and fat-soluble vitamins. Several studies have shown a significant risk of mortality in patients with cirrhosis and in liver transplantation recipients.2, 3, 4 The severity of presentation and risk of mortality is more in patients with decompensated cirrhosis.5,6 COVID-19 had lead to a significant decrease in number of liver transplant surgeries being performed, which would lead to an increased wait list mortality in these patients.

14.
Journal of Clinical and Diagnostic Research ; 16(9):FC15-FC19, 2022.
Article in English | EMBASE | ID: covidwho-2067197

ABSTRACT

Introduction: Long-term repercussions of Coronavirus Disease-2019 (COVID-19) on antimicrobial resistance have been raised as a grave concern due to the rampant use of antibiotics in the management of COVID-19. As per meta-analysis, the prevalence of antibiotic prescribing was 74.6% which was significantly higher than the estimated prevalence of bacterial co-infection. World Health Organisation (WHO) recommended that antibiotic therapy should not be used in patients with mild/moderate COVID-19 unless there is any bacterial suspicion. Also, the guidelines laid down by the Ministry of Health and Family Welfare, Government of India, does not recommend systematic empiric antibiotic therapy in patients hospitalised with COVID-19. Despite not being recommended, antimicrobials are still given in clinical practice. Aim(s): To analyse prescriptions for antimicrobials and to identify potential predictors for antibiotic prescription. Material(s) and Method(s): A retrospective observational study was conducted at a tertiary care teaching institute. Data (demographic profile, co-morbidities, disease category, prescribed antimicrobials, laboratory investigations, and duration of hospital stay) were collected from case files of patients with laboratory-confirmed Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection. These patients were admitted in the institute from January 2021 to May 2021. Logistic regression was used to analyse factors associated with the empirical use of antimicrobial agents. Result(s): A total of 184 case files were analysed. The mean age of patients was 55.84+/-15.72 years, with a male preponderance (70.10%). Among antimicrobials, antivirals were prescribed in 159 (86.41%) patients, and antibiotics in 152 patients (82.6%). Antivirals prescribed include Remdesivir [109(68.55%)] and Favipiravir [70(44.02%)]. Ceftriaxone was found to be the highest prescribed antibiotic, with a median duration of administration of six days. An association was found between disease severity and CRP level with antibiotic prescription. On multivariable analysis, the odds of receiving antibiotics were 6.7 times higher in patients with severe disease. Conclusion(s): More than 80% of COVID-19 patients received antibiotics. Duration of hospital stay was similar among patients whether they received antibiotics or not. Disease severity and raised CRP level were strong predictors for prescribing antibiotics for COVID-19. Copyright © 2022 Journal of Clinical and Diagnostic Research. All rights reserved.

15.
International Journal of Pharmacology ; 18(7):1340-1352, 2022.
Article in English | EMBASE | ID: covidwho-2066718

ABSTRACT

Paxlovid™ is a combination of Nirmatrelvir and Ritonavir antiviral pills with good oral bioavailability. In clinical studies, treatment of the patients infected with SARS-CoV-2 with Paxlovid™ within three to five days of the appearance of symptoms significantly reduced the hospitalization rate as well as mortality. It is the first oral antiviral treatment for the COVID-19 which received USFDA approval for EUA on 22nd December, 2021. Nirmatrelvir inhibits the replication of SARS-CoV-2 while another antiviral drug, Ritonavir, is given in combination to enhance the bioavailability of Nirmatrelvir. Molecular interaction studies have shown that Nirmatrelvir binds covalently with the catalytic triad of the active site of the viral protease enzyme (3CLPRO). It, therefore, acts by stopping the SARS-CoV-2 replication by its ability to block the translation of the viral genetic materials. Research studies conducted have proven the efficacy of this oral anti-viral drug in mild to moderate COVID-19 patients beside its ease of oral administration and good oral bioavailability. Alternative synthetic methods to scale up the synthesis of this potent molecule are needed to reduce the treatment cost of the COVID-19. Extensive clinical research on a larger group population is also underway for ensuring the safety and efficacy of this medication in the battle against the COVID-19 pandemic.

16.
Open Access Macedonian Journal of Medical Sciences ; 10:1058-1061, 2022.
Article in English | EMBASE | ID: covidwho-2066677

ABSTRACT

BACKGROUND: A novel coronavirus-caused pneumonia has been widespread worldwide since the end of 2019. The rapid widespread has prompted the repurposing of drugs based on promising in vitro and therapeutic results with other human coronavirus diseases. These repurposed drugs have mainly included remdesivir, favipiravir, lopinavirritonavir, ribavirin, interferons, and hydroxychloroquine. AIM: This study aims to evaluate the efficacy of any antiviral for 2019-nCoV infection in a national referral hospital. METHODS: This research was a retrospective study to evaluate all antiviral clinical responses used in a national referral hospital. RESULTS: Based on gender, there is a similar frequency from all patients. Hematology, followed by cardiovascular and pulmonary disease, is the most frequent comorbidity. There is no significant difference between the two groups antiviral treatment for a length of stay parameter. The most extended length of stay is 29 days. About 64.5% of patients are cured of SARS-Cov-2 infection. In the remdesivir group, we find that the mortality is significantly high. CONCLUSION: The clinical outcome of these antiviral treatments is similar, except for mortality. The severity of COVID-19 causes differences in mortality.

17.
Anti-Infective Agents ; 20(4) (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2065294

ABSTRACT

Background: SARS-CoV-2 infection has spread throughout the globe and has become a terrible epidemic. Researchers all around the globe are working to understand the characteristics of coronavirus and are trying to find antiviral compounds as an alternative to vaccines. Objective(s): The present study has been conceptualized to screen the various metabolites of traditional therapeutic plants that can have crucial antiviral activity against COVID-19. Method(s): Medicinal plants are rich sources of therapeutic agents of human origin. In this study, active metabolites from plants such as O. sanctum, C. longa, A. indica, Z. officinale, A. paniculata, G. glabra, A. sativum, P. guajava, V. negundo and S. aromaticum have been studied. This study aims to control COVID-19, either by interfering with the Cysteine-like protease (3CLpro) component of COVID-19 or by blocking viral entry via the human angiotensin-converting enzyme 2 (ACE 2) receptor. The molecular docking of forty plant metabolites was studied with the 3Clpro component and ACE 2 receptors. In addition to this, the binding capacity of these two targets was also compared with hydroxychloroquine used for its treatment. Result(s): The results reveal that Glycyrrhizin binds to 3CLpro in a highly stable manner with the lowest binding energy. Glabridin, beta-sitosterol, beta-Caryophyllene, alpha-Curcumene, and Apigenin, among others, have shown effective interactions with both ACE 2 and 3CLpro. The study reveals the ability of more than 20 plant-based compounds against the COVID-19 infection cycle, which are more effective than hydroxychloroquine. Conclusion(s): Medicinal plant-based therapeutic compounds might provide quickly, sensitive, precise, and cost-effective alternative therapies. To reduce adverse effects, many pharmacological characteristics of medicinal plant agents should be adjusted. Copyright © 2022 Bentham Science Publishers.

18.
Pharmaceutical Journal ; 307(7955), 2022.
Article in English | EMBASE | ID: covidwho-2065008
19.
Pharmaceutical Journal ; 306(7950), 2022.
Article in English | EMBASE | ID: covidwho-2064964
20.
Pharmaceutical Journal ; 305(7942), 2022.
Article in English | EMBASE | ID: covidwho-2064906
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