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1.
International Journal of Current Pharmaceutical Research ; 14(3):1-8, 2022.
Article in English | EMBASE | ID: covidwho-1929014

ABSTRACT

The Covid sickness (COVID19) pandemic is quickly expanding across the world. There is no legitimate therapy for this illness except for by supporting our resistance we can battle with this infection so to battle Coronavirus contamination the famous dietary enhancement bovine colostrums having bunches of utilization to battle against viral disease. It go about an immunomodulatory, anti-inflammatory, Antibacterial effect. The most significant part found in colostrum is lactoferrin which is a 80 KDA glycoprotein containing around 703 amino corrosive and having its capacity to tie with iron by restricting with iron, lactoferrin retain iron from the climate and forestalls viral heap of pathogens. The Covid didn't get authoritative therapy because of viral transformation;this review is accommodating for helping the invulnerable framework in coronavirus patient.

2.
Veterinary Evidence ; 7(2), 2022.
Article in English | EMBASE | ID: covidwho-1928966

ABSTRACT

Objective: To assess outcomes of a limited period (7 months) of remote video consultation with prescribing of prescription-only (POM) or prescription-only-veterinary (POM-V) medications by Royal College of Veterinary Surgeons (RCVS) registered veterinary surgeons to UK clients via a veterinary telemedicine smartphone application. Background: Objective evidence is needed to inform the veterinary profession on the impact that remote prescribing, without physical examination in person, has on animal health and welfare. During the COVID-19 pandemic, the RCVS allowed remote prescribing temporarily. Methods: Clinical records from all veterinary video consultations from 1 April-31 October 2020 were reviewed. Details were assessed pertaining to: signalment, body system/disease categories managed, referrals into practice, medication classes prescribed and outcomes following POM-V/POM medications. Records of adverse events and antimicrobial prescribing were reviewed. Results: 16.6% (3,541/21,383) of video consults had a POM-V/POM prescribed;with a (mild) adverse event rate of 0.8% (30/3541). Antibacterials were prescribed in 5.88% of all consultations (1,258/21,383), 99.3% (1249/1258) being first line. Follow-up on prescribing was available in 67.7% (2,399/3541) of cases. 89% (2135/2399) of all known treatment outcomes were complete or had an expected response to treatment. Dermatological disease was the most common body system/disease category seen and prescribed for. Conclusion: Low prescribing rates (including antibacterials) were recorded, treatments were efficacious and no harm was done by prescribing remotely via a veterinary video consult app. Application: Veterinary surgeons and governing bodies are invited to use the information provided in this clinical audit to inform decisions on the suitability of remote consultations and prescribing in veterinary medicine.

3.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927752

ABSTRACT

Rationale. Acute respiratory distress syndrome (ARDS) is a heterogeneous clinical disease. ARDS immunopathology due to lung infection involves an array of immune cells and the importance of granulocytes, and in particular neutrophils and neutrophil extracellular trap production (NETosis), has recently come to light. Despite over 20 well run, randomized, controlled trials, no specific therapies for ARDS are available and mortality remains high. Current treatments for ARDS are primarily limited to supportive therapies, including lung protective ventilation, and in certain situations, systemic steroid administration. Recently, clinical studies adding intravenous immunoglobulin (IVIG), an FDA approved drug, to standard ARDS therapy have shown faster recovery with less severe symptoms, suggesting a complementary beneficial effect, but the mechanism(s) remain unknown. Interestingly, previous in vitro studies found that IVIG can impair some inflammatory pathways in neutrophils. Our study assessed effects of IVIG with and without dexamethasone (a key glucocorticoid used in COVID-19 ARDS) in neutrophils ex vivo and in vivo in COVID-19 patients. Methods. Ex vivo treatment of neutrophils with IVIG or dexamethasone was conducted, followed by assessment of NETosis, oxidative burst and phagocytosis. Additionally, cell-free DNA was quantified in the blood of COVID-19 patients before and after treatment with IVIG. Ex vivo NETosis and plasma cell-free DNA was quantified using the QuantiT ™ PicoGreen™ dsDNA Assay Kit (Invitrogen). Oxidative burst was assessed by OxyBURST™ Green H2DCFDA, SE (Invitrogen) and phagocytosis of pHrodo™ Red S. aureus Bioparticles™ (Invitrogen) was quantified. Results. IVIG inhibits crucial neutrophil inflammatory pathways such as NETosis and oxidative burst while concomitantly enhancing phagocytic activity (Figure panels A-C). Notably, dexamethasone does not impact any of these critical pathways. Moreover, COVID-19 patients undergoing standard treatment plus IVIG had decreased cell-free DNA in the circulation 5 days after initiation of a 4 day treatment course, suggesting decreased NETs in circulation (Figure panel D) which possibly reverted at a later timepoint. Conclusion. Our data demonstrate potential targeted beneficial effects of IVIG in the context of neutrophil-mediated immunopathology. We demonstrate an ex vivo inhibitory effect of IVIG on pro-inflammatory pathways in neutrophils, which may lead to diminished immunopathology in disease states worsened by neutrophil-driven destruction. Based on the compelling evidence of the contribution of neutrophils to development and severity in ARDS, our evidence of IVIG impairing key pro-inflammatory functions in neutrophils (where dexamethasone does not) suggests a theoretical potential complementary beneficial effect of adding IVIG to standard treatment for infection induced ARDS although further research is needed.

4.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927721

ABSTRACT

Introduction: First synthesized in 1869, Hydroxyurea is known for its efficacy in treating myeloproliferative disorders, cervical cancer, and sickle cell disease. Usually well-tolerated, Hydroxyurea has numerous documented adverse effects, including bone marrow suppression, fevers, gastrointestinal upset, anorexia, and maculopapular rash. In addition, one rare side effect is interstitial pneumonitis, a potentially devastating complication if overlooked. We present one such case of Hydroxyurea-induced interstitial pneumonitis. Case Description: A 65-year-old man with a six-month diagnosis of Chronic Granulocytic Leukemia (CGL) on Hydroxyurea developed acute hypoxemic respiratory failure saturating 80% on room air with HR 102, RR 24, and increasing oxygen requirements (10 Lpm) after being admitted with complaints of worsening dyspnea, fatigue, and productive cough with yellow/green sputum. Physical examination was notable for cachexia, ill appearance, generalized weakness, hoarse voice, tachycardia, tachypnea, diffusely diminished breath sounds, and scattered rales on auscultation of lung fields. Initial imaging was notable for bilateral airspace disease and pulmonary opacities on chest radiography and bilateral pneumonia (concerning for COVID-19 pneumonia), mediastinal adenopathy, and splenomegaly on chest computed tomography. Initial laboratory results were notable for leukocytosis 62.5 th/uL, lactic acidosis 2.5 mmol/L, procalcitonin level 4.95 ng/mL, and negative COVID-19 PCR test. Prompt initiation of Vancomycin/Cefepime therapy ensued upon collection of blood cultures in light of possible sepsis. Flagyl, Valacyclovir, and Posaconazole were added to antimicrobial coverage, along with steroid therapy, due to minimal clinical improvement. Tachycardia with significant oxygen requirements alternating between BiPAP and heated high flow nasal cannula with FiO2 ranging from 70-85% persisted. Daily imaging also showed worsening airspace disease. Negative viral, bacterial, and fungal cultures led to subsequent discontinuation of Hydroxyurea therapy due to suspicion of medicationinduced pneumonitis. Three days after cessation of Hydroxyurea, the patient's oxygen requirements began to decrease and imaging revealed interval resolution of pneumonitic changes in the absence of antimicrobial therapy. The patient was later transitioned to Ruxolitinib for his underlying CGL prior to his discharge home without the need for home oxygen therapy. Discussion: Thought to be caused by hypersensitivity pneumonitis, pulmonary toxicity from Hydroxyurea can easily be misdiagnosed. Unfortunately, while much is known about the pancytopenic, gastrointestinal, and cutaneous side effects of Hydroxyurea, few cases in the literature highlight the potentially fatal interstitial pneumopathy caused by Hydroxyurea, first reported in 1999. Thus, this case serves as an additional contribution to the minutiae of literature detailing Hydroxyurea's adverse pulmonary side effect profile. (Figure Presented).

5.
Journal of Young Pharmacists ; 14(2):140-155, 2022.
Article in English | EMBASE | ID: covidwho-1918025

ABSTRACT

Since December 2019 world faces a respiratory pandemic named Coronavirus disease-19 (COVID-19). COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The term epidemic was coined by Hippocrates who is considered the father of Unani medicine which is based on four humours. In the Unani System of Medicine (USM) equivalent term for the epidemic is Wabā'. In classical Unani literature symptoms of Nazla-i-Wabā'iyya and Humma-i-Wabā'iyya closely resemble the symptoms of COVID-19. Major manifestations of this outbreak are cough, fever, headache, nausea, and breathlessness. This pandemic takes place due to a change in the quality of the surrounding air. We searched different databases electronically using the terms “COVID-19 or Coronavirus”, “Wabā or infectious disease”, “Unani immunomodulators”, ''Herbal immunomodulators'', ''Anti-viral herbal drugs'', Herbal fumigation and “Nazla-i-Wabā'iyya or Nazla Wabā'ī”. We also gone through different classical textbooks of USM available in the NRIUMSD library. We reviewed the concept of Wabā', its prevention, and management strategies available in USM. We also searched antiviral, immunomodulation, fumigation activities of Unani drugs. Unani physicians advocated general measures of physical distancing, health hygiene, isolation, quarantine, and immunomodulation. As a preventive measure, various immunomodulatory drugs like Asgandh, Aam, Babuna, Gilo, Satawar, and Kalonji and antidotes such as Tiryāq Wabā'i have been described in the literature. The ingredients of Tiryāq-i-Wabā'i include Aloe barbedensis, Crocus sativus, and Commiphora myrrha. Several fumigants like Sandal, Ood, Kafoor, Loban, and Jhau are also mentioned in the management of the epidemic. For symptomatic management various antiviral, antipyretic and antitussive drugs are described well. Many evidence-based studies have already been reported for single drugs and formulations used in the USM.The Khamira Marwareed possesses antiviral, cardiotonic, and immunomodulatory activity. Single drugs such as Khaksi, Asgandh, Adusa, Chiriata, and Zanjabeel possess antipyretic, immunomodulatory, antitussive, antibacterial, and antiviral activities respectively. The knowledge from classical Unani literature and scientific researches may be useful in the prevention and management of COVID-19 like epidemic diseases. This review article aims to find out the concept of the pandemic, prevention, and management strategies existing in the USM.

6.
Clinical Toxicology ; 60(SUPPL 1):96-97, 2022.
Article in English | EMBASE | ID: covidwho-1915435

ABSTRACT

Objective: Numerous national and international publications highlight an increase in enquiries for exposures to disinfectants and antiseptics related to the COVID-19 pandemic. The data published in the literature, however, are limited to analyzing the months corresponding to the first period of confinement, while data relating to the second and third pandemic waves are lacking. Our aim was to analyse these exposures in the months following the wave of the pandemic. Methods: We used descriptive statistics to analyse toxicology consultation volumes to hypochlorite bleaches, disinfectants and antiseptic products for the period 1 February 2020-3 May 2020 (first lockdown), 1 October 2020-31 December 2020 (second lockdown) and we compared these data with that relating to the same periods of 2019 and the period 1 February 2021-3 May 2021. Results: Compared to 2019, accidental exposures to all the products considered in the study showed an increase of 67.9% in the period February-May 2020, an increase of 26.3% in the period October-December 2020 and an increase of 16.9% in the period February-May 2021. (Table 1). During the period February-May 2020 the respective increases compared to the same period of 2019 were: bleaches (+45.7%), antiseptics (+61.7%), disinfectants (+140.2%);for the period October-December 2020 the respective increases compared to the same period of 2019 were: bleaches (+0.3%), antiseptics (+43.2%), disinfectants (+113%). During the period from February to May 2021 compared to 2019 changes were as follows: bleaches (-9.7%), antiseptics (+44.3%), disinfectants (+59%). Respiratory symptoms were present in the majority of cases, followed by gastrointestinal, oropharyngeal, ocular and other routes. Conclusion: The data highlight how the effect of the COVID-19 pandemic on exposures to antiseptic and disinfectant products in Italy did not end with the first wave, but persists, although with smaller numbers, even in the period of the second wave and in early 2021. (Table Presented).

7.
Indian Journal of Animal Sciences ; 92(2):166-173, 2022.
Article in English | EMBASE | ID: covidwho-1913183

ABSTRACT

Antimicrobial resistance (AMR) is a silent pandemic faced parallel to COVID-19 pandemic, owing to indiscriminate usage of antimicrobial agents by large mass of people as part of self-medication and unsupervised therapy protocols. This similar kind of situation does exist in livestock and poultry farming sector, which has led to AMR issues like Methicillin-resistant Staphylococcus aureus (MRSA) mastitis. AMR is really an alarming issue which needs to be addressed or else in near future it would be difficult to treat or control infections in both humans and animals. Reduction in indiscriminate antimicrobial usage and AMR issues in animal husbandry sector requires intervention in animal husbandry practices. In order to device such intervention practices, first we need to document the field level antibiotic usage and knowledge level on AMR. But unfortunately, data on AMR issues at field level were deficit and poorly documented in India. Hence this cross-sectional study was carried out to explore the knowledge and usage pattern of antibiotics among livestock and poultry farmers of Telangana state of India through direct interview method. Cent per cent of the farmers responded that antibiotics were used mainly for therapeutic purpose followed by prophylactic (32%), metaphylactic purpose (44.5%) and as growth promoters (8.33%). Farmers (78%) responded that they purchase the antimicrobial agents over-the-counter. Oxytetracyclines and Enrofloxacin were the two major antibiotics used abundantly by the livestock farmers. Large proportions of famers (80%) were neither following full dosage regime of antimicrobial used nor the withdrawal period, while antimicrobial usage on their animals owing to lack of awareness and knowledge regarding the AMR. Significant differences were found amongst the livestock and poultry farmers with respect to their knowledge level on antimicrobial usage and AMR in animals.

8.
International Journal of Green Pharmacy ; 16(1):24-34, 2022.
Article in English | EMBASE | ID: covidwho-1897280

ABSTRACT

Withania somnifera (L.) Dunal is a valuable plant of family Solanaceae, which is commonly known as Asgand in Unani system of medicine (Tibb-e-Unani). The plant is found throughout the drier parts of India and other parts of the world. The main drug component comprises of the roots that is used for its therapeutic actions either singly or as an ingredient in compound formulations. Asgand is well described in Unani classics as Musakkin (sedative), Muqawwi (tonic) Muhallil-e-waram (anti-inflammatory), Muaddil (alterative), and Muqawwi-e-Bah (aphrodisiac). In Unani system, it is prescribed for rheumatism, gynecological disorders, cough, hiccup dropsy, and as a sedative in cases of senile debility. Studies indicate that the pharmacological activities of the root and leaf are attributed to the presence of several alkaloids and steroidal lactones including withanine, somniferine, somnine, and somniferinine. Leaves contain a group of (nearly twelve) “Withanolides” including “Withaferin-A” with antibiotic and anti-tumor activity. Asgand possesses anti-inflammatory, antioxidant, anxiolytic, adaptogenic, memory enhancing, antiparkinsonian, and antitumor properties. Several other effects such as immuno-modulation, cardiovascular protection, hypolipidemic, antibacterial, and sexual behavior, tolerance have also been studied. In conventional Unani system, enhancing immunity with immune-boosters is one of the key approaches for prevention of disease and maintenance of health. An attempt has been made in this review to explore the various dimensions of the drug viz;morphological, pharmacological, chemical studies and more specifically the therapeutic actions, uses and Unani perspective of Asgand in the time of Covid-19.

9.
International Journal of Research in Ayurveda and Pharmacy ; 13(3):21-26, 2022.
Article in English | EMBASE | ID: covidwho-1897166

ABSTRACT

Hand hygiene is crucial as it gets contaminated easily from direct contact with airborne microorganism droplets and droplet nuclei from coughs and sneezes. In situations like a pandemic outbreak of COVID-19, it is imperative to interrupt the transmission chain of the pathogens by the practice of proper hand sanitization. It can be achieved with contact isolation and strict infection control tools like maintaining good hand hygiene in the house, in hospital settings, and in public. The success of hand sanitization solely depends on practical hand disinfecting agents formulated in various types and forms, such as antimicrobial soaps and water-based or alcohol-based hand sanitiser, with the latter being widely used in hospital settings and by common people. Most effective hand sanitiser products are alcohol-based formulations containing 62%–95% of alcohol as they can denature the proteins of microbes and the ability to inactivate pathogens. Considering the need, we prepared five herbal hand sanitizers in Arka form using drugs of krimighna gana dravyas that have an antimicrobial property and are volatile. Among all the five preparations, it was noticed from the statistical analysis, that there was a significant reduction in the bacterial count in the ‘immediate application’ of Batch I (Tulsi Arka), and Batch II (Tulsi, Nimba Arka) showed a significant decrease in the bacterial count in ‘after 30 minutes of application’. However, Batch III (Tulsi, Nimba, Haridra arka) gave an intermediate result in ‘immediate application’ and ‘after 30 minutes of application’. None of the preparations showed any sort of irritation, dryness or discomfort to the subjects even after 30 minutes while conducting the study.

10.
Recent Patents on Biotechnology ; 16(1):79-80, 2022.
Article in English | EMBASE | ID: covidwho-1887056
11.
Medicine and Pharmacy Reports ; 95(2):1-4, 2022.
Article in English | EMBASE | ID: covidwho-1885098
12.
International Journal of Pharmaceutical Research ; 12(4):5329-5338, 2020.
Article in English | EMBASE | ID: covidwho-1884955

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), has been responsible for a respiratory tract disease which has taken the proportion of the pandemic (COVID-19) ravaging the planet for last 2 and half year. The COVID-19 pandemic has been responsible for about sixty-one million deaths and about 500 million infections worldwide. The medication of infected individuals has been mainly cantered around repurposing of available known antiviral drugs, immunosuppressor/ immunomodulator drugs, monoclonal antibody concoctions and various vaccines as prophylaxis measures. Use phytometabolites in studies have been found to very effective in counter the SARS-CoV-2 spike protein binding sites, the main step to virus attack on the respiratory epithelial cells. Lichen secondary metabolites are well known for their antimicrobial, immunomodulator and antiviral activities. Current study was done to assess the spike protein binding capabilities of some lichen secondary metabolites of SARS-CoV-2 (Wuhan strain) spike protein binding sites using in-silico docking modelling. The study found that some of the lichen metabolites such as Cryptostictic acid and Quaesitic acid were effective in blocking the target cell recognising regions of the SARS-CoV-2 spike protein and can be effectively developed as therapeutic medicine.

13.
Antibiotiki i Khimioterapiya ; 67(1-2):24-31, 2022.
Article in Russian | EMBASE | ID: covidwho-1870325

ABSTRACT

Although antibiotics (AB) are ineffective for the treatment of COVID-19, they are often prescribed to patients with the novel coronavirus infection (NCV) for a variety of reasons. They include the difficulty of excluding bacterial co-infection at the first contact with the patient, as well as the possibility of developing a secondary bacterial infection. The aim of the work is to assess the frequency and background of prescribing antibiotics to hospitalized patients with confirmed COVID-19. Material and methods. A retrospective analysis of 160 hospital records of patients with confirmed COVID-19, who were treated in various Infectious Diseases Departments during the period from September to October 2020, was carried out. The selection was done by the method of random sampling. The analysis did not include the records of patients admitted to the ICU for NCV. Results. Information aboutthe appointment of antibacterial drugs before hospitalization was found in 109 patients, of which only 51 patients did not receive AB on an outpatient basis. The remaining 58 (53.2%) patients began taking ABs on their own or based on the recommendation of an outpatient doctor, including 31 patients who took two or more drugs (successively or simultaneously). The most commonly used antibiotics were: macrolides (37 patients), cephalosporins (24 patients), respiratory fluoroquinolones (12 patients), and aminopenicillins (5 patients). On admission, AB was prescribed for almost all patients, except for one. The most frequently prescribed antibiotics were: macrolides (61%), mainly azithromycin, and respiratory fluoroquinolones (54.1%), mainly levofloxacin. In most cases, these drugs were combined with 3rd or 4th generation cephalosporins. Most patients received more than one AB: two drugs were prescribed to 86 (54.1%) patients, three - to 34 (21.4%) patients. AB therapy was carried out for a long time: the maximum number of days for macrolide administration (excluding previous AB therapy at the outpatient stage) was 16 days, respiratory fluoroquinolones - 22 days, 3rd generation cephalosporins - 19 days, 4th generation cephalosporins - 17 days, carbapenems - 34 days. In almost 100% of cases, ABs were prescribed on the first day of admission of patients, and their therapy continued until the patient was discharged from the hospital. Conclusion. The appointment of antibiotics at the hospital stage was established for the vast majority of patients in the absence of clear indications for their appointment. Such a frequent prescription of antibiotics is accompanied by a number of problems: immediate - side effects of such therapy (for example, antibiotic- associated diarrhea), long-term - an increase in antibiotic resistance of microorganisms.

14.
Vestnik Rossiiskoi Akademii Meditsinskikh Nauk ; 77(1):25-32, 2022.
Article in Russian | EMBASE | ID: covidwho-1870166

ABSTRACT

Background. One of the complications in patients hospitalized with COVID-19 is a secondary bacterial infection. Its frequency can reach 15%, which makes it important to determine the etiology and antimicrobial resistance of the key pathogens responsible for the development of this pathology, in order to further improve the practice of prescribing and increase the effectiveness of antimicrobial chemotherapy. Aims — to assess the etiological structure and antibiotic resistance of the main pathogens of SBIs to improve the practice of antibiotic prescription. Methods. This retrospective study reviewed medical records of the patients hospitalized with COVID-19 in the Moscow city hospital No. 4 between April 28 and November 1, 2020. Demographic, clinical outcomes, etiology, and antimicrobial resistance data of the SBIs were collected. Outcomes were also compared between patients who were classified as severe and critical on admission. Results. Among 3180 patients hospitalized with COVID-19, 220 (6.9%) patients had acquired SBIs, and 50.0% of cases were fatal. The mean age was 72.7 ± 13.07 years. A higher mortality rate was observed in the group of critical patients (63%). 560 strains of bacteria isolated from the SBIs (58.8% isolated from lungs, 21% from urine and 20.2% from blood). 330 strains (58.9%) were Gram-negative bacteria. 109 patients had infections with mixed bacteria. 45 of them (20.5% of the total number of patients included in the study) had 2 pathogens, and 64 patients (29.1%) 3 or more strains. The top three bacteria of SBIs were A. baumannii (23.6%;132/560), K. pneumoniae (22.9%;128/560), and S. epidermidis (10.4%;58/560). The isolation rates of carbapenem-resistant A. baumannii were 97%. Cefoperazone/sulbactam was the most active antibiotic against this pathogen with 62.1% sensitivity. Among K. pneumoniae strains, the level of resistance to carbapenems was 77.4% to meropenem and 54% to imipenem. The proportion of resistant strains to tigecycline and to colistin was 4 and 2.3% respectively. Meticillin resistance was present in 38.5% of S. aureus. 50% of E. faecium strains were vancomycinresistant. Conclusions. Gram-negative bacteria, especially A. baumannii and K. pneumoniae, were the main pathogens, and the resistance rates of the major isolated bacteria were generally high, which indicates that more accurate use of antibacterial agents is necessary for SBIs in patients hospitalized with COVID-19.

15.
Asian Pacific Journal of Tropical Medicine ; 15(2):87-89, 2022.
Article in English | EMBASE | ID: covidwho-1869925

ABSTRACT

Rationale: Human myiasis is the invasion of tissue or organs by fly larvae. This could be obligatory, facultative, or accidental. Patient concerns: A 4-year-old Saudi boy complained of fever over the past three days with multiple inflamed painful dermal furuncles and worms-like discharge. Diagnosis: Furuncular obligatory myiasis caused by Wohlfahrtia magnifica. Interventions: Maggots were removed for identification. The wounds were cleaned with antiseptic dressings. Topical and oral antibiotics were applied. Outcomes: Seven days later, the wounds completely healed. Lessons: Although several reports correlated human myiasis with old age, low health status, mental retardation, and low socioeconomic status, but the patient in our case was a healthy child from a family with good socioeconomic status, good hygiene, no history of diseases or mental disability, but traveled to a village where the climate is suitable for fly breeding.

16.
Letters in Drug Design and Discovery ; 19(5):413-427, 2022.
Article in English | EMBASE | ID: covidwho-1862452

ABSTRACT

Background: COVID-19, first reported in China, from the new strain of severe acute respiratory syndrome coronaviruses (SARS-CoV-2), poses a great threat to the world by claiming uncountable lives. SARS-CoV-2 is a highly infectious virus that has been spreading rapidly throughout the world. In the absence of any specific medicine to cure COVID-19, there is an urgent need to develop novel thera-peutics, including drug repositioning along with diagnostics and vaccines to combat the COVID-19. Many antivirals, antimalarials, antiparasitic, antibacterials, immunosuppressive anti-inflammatory, and immunoregulatory agents are being clinically investigated for the treatment of COVID-19. Objectives: The earlier developed one parameter regression model correlating the dock scores with in vitro anti-SARS-CoV-2 main protease activity well predicted the six drugs viz remdesivir, chloroquine, favipiravir, ribavirin, penciclovir, and nitazoxanide as potential anti-COVID agents. To further validate our earlier model, the biological activity of nine more recently published SARS-CoV-2 main protease inhibitors has been predicted using our previously reported model. Methods: In the present study, this regression model has been used to screen the existing antiviral, an-tiparasitic, antitubercular, and anti pneumonia chemotherapeutics utilizing dock score analyses to explore the potential including mechanism of action of these compounds in combating SARS-CoV-2 main prote-ase. Results: The high correlation (R=0.91) explaining 82.3% variance between the experimental versus predicted activities for the nine compounds is observed. It proves the robustness of our developed model. Therefore, this robust model has been further improved, taking a total number of 15 compounds to formu-late another model with an R-value of 0.887 and the explained variance of 78.6%. These models have been used for high throughput screening (HTS) of the 21 diverse compounds belonging to antiviral, an-tiparasitic, antitubercular, and anti pneumonia chemotherapeutics as potential repurpose agents to combat SARS-CoV-2 main protease. The models screened that the drugs bedaquiline and lefamulin have higher binding affinities (dock scores of-8.989 and-9.153 Kcal/mol respectively) than the reference compound {N}-[2-(5-fluoranyl-1~{H}-indol-3-yl)ethyl]ethanamide (dock score of-7.998 Kcal/Mol), as well as higher predicted activities with pEC50 of 0.783 and 0.937 µM and the 0.611 and 0.724 µM respectively. The clinically used repurposed drugs dexamethasone and cefixime have been predicted with pEC50 val-ues of-0.463 and-0.622 µM and-0.311 and-0.428 µM respectively for optimal inhibition. The drugs such as doxycycline, cefpodoxime, ciprofloxacin, sparfloxacin, moxifloxacin, and TBAJ-876 showed moderate binding affinity corresponding to the moderate predicted activity (-1.540 to-1.109 µM). Conclusion: In the present study, validation of our previously developed dock score-based one parametric regression model has been carried out by predicting 9 more SARS-CoV-2 main protease inhibitors. Another model has been formulated to explore the model's robustness. These models have been taken as a barometer for the screening of more potent compounds. The HTS revealed that the drugs such as bedaqui-line and lefamulin are highly predicted active compounds, whereas dexamethasone and cefixime have optimal inhibition towards SARS-CoV-2 main protease. The drugs such as doxycycline, cefpodoxime, ciprofloxacin, sparfloxacin, moxifloxacin, and TBAJ-876 have moderately active compounds towards the target inhibition.

17.
Deutsche Apotheker Zeitung ; 162(8), 2022.
Article in German | EMBASE | ID: covidwho-1857852
18.
RSC Drug Discov. Ser. ; 2022-January:101-128, 2022.
Article in English | EMBASE | ID: covidwho-1852525

ABSTRACT

Screening advanced compounds enables discovery of direct repurposing candidates, novel drug-like leads for optimization, and informative pharmacological probes. In this chapter, we describe different types of screening collections used in drug repurposing, discuss issues and considerations in preparing and executing a repurposing screen, and present examples of in vitro and in vivo repurposing assays. We further describe various data sources reporting information on de-risked compounds of different types and illustrate how data mining and chemoinformatic and chemogenomic searches can be used to access large numbers of advanced compounds and assemble collections most suitable for screening in a given disease model. We argue that a view of repurposing screening as a large-scale bet on finding candidates for clinical testing is narrow and incomplete. Rather, when thoughtfully executed, screening of re-risked compounds is informed by target pathobiology and offers a means to efficiently convert advances in the development of sophisticated non-clinical models and new insights in disease mechanisms into novel drug-like leads and candidates for development.

19.
Clinical Cancer Research ; 27(6 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1816879

ABSTRACT

The main causative agent for the global pandemic of COVID-19 is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Developing therapeutic strategies to stop the virus is the hour of need. According to the recent clinical reports, it is seen that an androgen-regulated host cell serine protease TMPRSS2 acts on the spike protein of the SARS-CoV-2 virus which interacts with the host angiotensin-converting enzyme 2 (ACE2) and enters the host cell to cause the infection. Reports also suggest that TMPRSS2 is regulated by androgen present in prostate cells and it is highly expressed in PCa patients. Our lab has recently synthesized a new cisplatin prodrug which is a conjugate of lauric acid and cisplatin that potentially works very effectively in various androgen dependent and independent prostate cancer (PCa) cells. The cisplatin prodrug unlike other conventional platinum drugs is involved in inhibition of one of the major metabolic pathways of the PCa cells. Preliminary results show that, the prodrug in combination with the anti-androgen bicalutamide has an increased inhibition on the expression of TMPRSS2 in androgen dependent PCa and lung carcinoma cells along with down-regulation of some the lipogenic enzymes in-vitro. Here, we propose that the prodrug inhibits one of the mitochondrial metabolic pathways making the PCa cells sensitive towards cisplatin-based chemotherapy along with reducing the expression of TMPRSS2. Once completed, our work will provide an inside story of cisplatin prodrug mediated alteration of lipogenesis of cells in PCa tumor microenvironment resulting in a platform that has the potential to reduce the burden of cancer aggressiveness in both androgen dependent and independent PCa and also can be used as a potent chemotherapeutic agent against COVID-19.

20.
International Journal of Pharmacy Practice ; 30(SUPPL 1):i6-i7, 2022.
Article in English | EMBASE | ID: covidwho-1816110

ABSTRACT

Introduction: Few qualitative studies have explored determinants of antimicrobial prescribing behaviour in hospitals, and none has made reference to behavioural theories. An understanding of these determinants is required for the successful development and implementation of behaviour change interventions (BCIs) in this area. Aim: To explore the determinants of clinicians' antimicrobial prescribing behaviour, using the Theoretical Domains Framework (TDF;a framework of behavioural theories). Methods: This work was part of a multi-phase explanatory, sequential mixed methods PhD programme of research. This qualitative part involved semi-structured, online (video) interviews via a videoconferencing software programme (Zoom) with clinicians (doctors and pharmacists) based in 12 Hamad Medical Corporation hospitals in Qatar. Clinicians were sampled purposively in strata of gender, profession, years of experience and area of practice. The interview schedule was developed based on a review of published literature (1), previous findings of quantitative research (2) and the TDF to ensure comprehensive coverage of key determinants (including barriers and facilitators) related to clinicians' antimicrobial prescribing behaviour. Interviews were conducted from December 2020 to February 2021, audio-recorded, transcribed and independently analysed by two research team members using the TDF as an initial coding framework. Results: Data saturation was achieved after interviewing eight doctors and eight pharmacists from a range of areas of practices and with a variety of experiences. A number of themes, linked to ten TDF domains, were identified as determinants of antimicrobial prescribing behaviour and these determinants were interrelated. In-depth analysis identified several barriers and facilitators that may contribute to inappropriate or appropriate antimicrobial prescribing. Main barriers identified were around hospital guidelines and electronic system deficiencies (environmental context and resources), gaps in the knowledge in relation to guidelines and appropriate prescribing (knowledge), restricted roles/responsibilities of microbiologists and pharmacists (professional role and identity), uncomfortable antimicrobial prescribing decisions (memory, attention and decision processes), as well as professional hierarchies and poor multidisciplinary teamworking/relationships (social influences). Sometimes, the barrier would be the ego of senior doctors who refuse our evidence-based recommendation and depend on their clinical judgement or experience (Pharmacist 470, Cardiology). Key facilitators highlighted included guidelines compliance goals and intentions, and the beliefs of consequences of appropriate or inappropriate prescribing. Further education and training sessions, and some changes to guidelines, including accessibility were also considered essential. We need to seriously consider getting an antibiotic guidelines app which is downloaded to clinicians' mobile phones. The mobile app is handy, you can access it anytime even at the patient's bedside (Doctor 514, Microbiology). Conclusion: This qualitative study, using a theoretically based approach, has identified that antimicrobial prescribing in hospitals is a complex process influenced by a broad range of behavioural determinants that described specific barriers and facilitators. The in-depth understanding of this complexity provided by this phase of the research may contribute to the design and development of theoretically based BCIs to improve clinicians' antimicrobial prescribing. Limitations include data collected with online interviews due to the Covid-19 restrictions. This may have excluded some clinicians who did not feel comfortable with or have access to the technology required.

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