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1.
Romanian Journal of Neurology/ Revista Romana de Neurologie ; 21(2):172-178, 2022.
Article in English | EMBASE | ID: covidwho-1957675

ABSTRACT

Objective. Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological symptoms. To compare the clinical features, imaging and treatments in patients with and without COVID 19. To compare the mortality and in-hospital stay among patients with and without COVID 19 and negative patients. Materials and methods. In this retrospective, single-center study, we included all the patients who attended the department of neurology with neurologic symptoms with confirmed COVID-19 and long COVID-19 from June 2020 to January 2021. Data on clinical signs, diagnosis, laboratory findings were collected and analyzed from the records for positive patients and compared with neurologic patients without COVID-19 admitted in the same period. Statistical analysis: The mean values between study groups were compared using an independent sample t-test and Mann Whitney u test. Categorical outcomes were compared using the Chi square test. Data was analyzed using coGuide soft-ware. Results. Headache was the common neurologic manifestation present in COVID positive patients compared to COVID negative patients (39.13%). There was no statistically significant difference between the two groups in baseline parame-ters. Laboratory parameters like CRP, Serum Ferritin, LDH, D-dimer, ESR, and IL-6 showed a significant increase in COVID positive patients (P <0.05). In-hospital mortality was more in COVID positive patients than COVID negative patients (P <0.011). Conclusion. The study showed varied neurologic symptoms in COVID patients, with headache as the common symptom. Hospital stay, morbidity, mortality, and inflammatory parameters were more in COVID positive patients compared to COVID negative patients.

2.
Indian Journal of Forensic Medicine and Toxicology ; 16(2):326-333, 2022.
Article in English | EMBASE | ID: covidwho-1957671

ABSTRACT

Coronavirus disease 2019 discovered in December 2019, Wuhan, China. It was transmitted globally producing the present COVID-19 pandemic. Concerns have been raised about the potential impact of COVID-19 on male reproductive organs and male fertility as the number of infections in the male community has increased. The objectives of current study are studying the relationship between the plasma levels of testosterone and the markers of immune reaction with the severity and mortality in a sample of COVID-19 patients. A cross section study included NO= 103 male patients affected by SARS-CoV-2 pneumonia, diagnosed by PCR and chest CT scan, (≥ 18 years old), and recovered in the respiratory intensive care unit (RICU). Several biochemical risk factors were determined Free Testosterone, sex hormone binding globulin (SHBG) were measured by Enzyme-Linked Immunosorbent Assay(ELISA), D-dimer, Ferritin, CRP, Urea, Creatinine were measured by automated method by using Abbott Architect c4000 and Complete Blood Count(CBC). The results show that the serum free testosterone and SHBG levels a significant lower in non-survivor patients than survivor patients with COVID-19. While the other biomarkers (D-dimer, Ferritin, Urea, Creatinine) were significant higher in non-survivor patients than survivor patients. The CRP, WBC and lymphocyte showed that no significant between the both group of patients. In conclusion the study showed that lower free testosterone and SHBG levels enable significant role in increasing risk of COVID-19 mortality amongst adult male patients.

3.
Indian Journal of Pharmaceutical Sciences ; 84(3):617-630, 2022.
Article in English | EMBASE | ID: covidwho-1957666

ABSTRACT

Drug repositioning may be a promising way to find potential therapies against coronavirus disease 2019. Although chloroquine and hydroxychloroquine showed controversial results against the coronavirus disease 2019 disease, the potential common and diverging mechanisms of action are not reported and need to be dissected for better understanding them. An integrated strategy was proposed to systematically decipher the common and diverging aspects of mechanism of chloroquine and hydroxychloroquine against coronavirus disease 2019-disease network based on network pharmacology and in silico molecular docking. Potential targets of the two drugs and coronavirus disease 2019 related genes were collected from online public databases. Target function enrichment analysis, tissue enrichment maps and molecular docking analysis were carried out to facilitate the systematic understanding of common and diverging mechanisms of the two drugs. Our results showed that 51 chloroquine targets and 47 hydroxychloroquine targets were associated with coronavirus disease 2019. The core targets include tumor necrosis factor, glyceraldehyde 3-phosphate dehydrogenase, lymphocyte-specific protein-tyrosine kinase, beta-2 microglobulin, nuclear receptor coactivator 1, peroxisome proliferator-activated receptor gamma and glutathione disulfide reductase. Both chloroquine and hydroxychloroquine had good binding affinity towards tumor necrosis factor (affinity=-8.6 and -8.4 kcal/mol, respectively) and glyceraldehyde 3-phosphate dehydrogenase (-7.5 and -7.5 kcal/mol). Chloroquine and hydroxychloroquine both had good affinity with angiotensin-converting enzyme 2, 3-chymotrypsin-like protease and transmembrane serine protease 2. However, hydroxychloroquine manifested better binding affinity with the three proteins comparing with that of chloroquine. Chloroquine and hydroxychloroquine could have potential to inhibit over-activated immunity and inflammation. The potential tissue-specific regulation of the two drugs against severe acute respiratory syndrome coronavirus 2 infection may related with the lung, liver, brain, placenta, kidney, blood, eye, etc. In conclusion, our data systematically demonstrated chloroquine and hydroxychloroquine may have potential regulatory effects on coronavirus disease 2019 disease network, which may affect multiple organs, protein targets and pathways. Routine measurements of the chloroquine and hydroxychloroquine blood concentrations and tailored therapy regimen may be essential. But, further rigorous and high quality randomized controlled clinical trials are warranted to validate the antiviral effects of chloroquine and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2. Our proposed strategy could facilitate the drug repurposing efforts for coronavirus disease 2019 treatment.

4.
Indian Journal of Pharmaceutical Sciences ; 84(3):519-531, 2022.
Article in English | EMBASE | ID: covidwho-1957665

ABSTRACT

The severe acute respiratory syndrome coronavirus 2, formerly known as 2019 novel coronavirus, the causative pathogen of coronavirus disease 2019 is a major source of disaster in the 21st century. In the second meeting of the Emergency Committee, the World Health Organization declared that coronavirus disease 2019 is a "public-health emergency of international concern" on 30 January, 2020. Coronavirus is transmitted via airborne droplets from human to human or human to animal. Through membrane angiotensin-converting enzyme 2 exopeptidase receptor coronavirus enters in human cell. For the treatment of this sudden and lethal disease during coronavirus disease 2019, there are no specific anti-virus drugs or vaccines. Still, the development of these medicines will take months, even years. Currently there is need of supportive care and non-specific treatment to improve the symptoms of coronavirus disease 2019 infected patient. For this specific indication, rapid performance of herbal medicine or phytochemicals can contribute as an alternative measure. Phytochemicals are a powerful group of chemicals that are derived from plants origin hence causing fewer side effects because of less use of additives, preservatives or excipients. Hence, this review will focus on some phytochemicals which may control and prevent severe acute respiratory syndrome coronavirus 2. Further, the existing healing options, drugs accessible, ongoing trials and current diagnostics to treat severe acute respiratory syndrome coronavirus 2 have been discussed. We suggested phytochemicals extracted from herbal plants are potential novel therapeutic approaches, completely targeting severe acute respiratory syndrome coronavirus 2 and its pathways.

5.
Trends in Pharmaceutical Sciences ; 8(2):95-106., 2022.
Article in English | EMBASE | ID: covidwho-1957649

ABSTRACT

We have explored the inhibitory capability of Thymus vulgaris compounds against ACE2 protein -the host receptor for SARS-CoV-2, papain-like and main protease of the SARS-CoV-2 through molecular simulations. The docking results showed that the compounds had a greater capability to inhibit ACE2 and papain-like protease in comparison to the main protease. The majority of compounds (61.7%) bind to the S2 active pocket of ACE2. The most powerful anticoronavirus activity is expressed in the order: Terpinolene > Thymol > Bicyclogermacrene. Pi interactions play key roles in the binding of three compounds to the active sites of ACE2 enzyme. 34 out of these 60 compounds were fitted in the PLpro active site. α-humulene followed by (+)-Spathulenol, and (-)-β-Bourbonene showed strong capacity to inhibit PLpro binding site. Except for (+)-Spathulenol which also formed H-bond with Asp165 and Tyr274 amino acids, α-humulene and (-)-β-Bourbonene conjugate with PLpro were stabilized mainly through alkyl and pi interactions. According to the Mpro docking results, 58.3% of thyme compounds could block the active site. The binding energy order was (-)-Spathulenol at highest, then Bicyclogermacrene, (+)-δ-cadinene, (+)-Spathulenol, and Viridiflorol, followed by (-)-β-Caryophyllene oxide. Cys145, His41, Met49, and Met165 are key residues in the interaction of these ligands with the enzyme binding site. The weakest interaction with all three enzymes was observed for (R)-(-)-1-Octen-3-ol and (3S)-Oct-1-en-3-ol. Based on the molecular dynamics simulation lowest conformational change was detected for ACE2 in the present of Terpinolene. (-)-Spathulenol and α-Humulene had the least and most displacement compared to its initial positions, respectively.

6.
Rational Pharmacotherapy in Cardiology ; 18(3):282-288, 2022.
Article in Russian | EMBASE | ID: covidwho-1957626

ABSTRACT

Aim. To study the dynamics of the lipid profile of hypertensive patients with dyslipidemia who underwent COVID-19. Material and methods. Hypertensive patients with dyslipidemia who underwent COVID-19 [n=126;58 men and 68 women;median age 60 (56.0;65.5) years] examined. Patients were included into two groups: group 1 (n=64) received a single pill combination of lisinopril + amlodipine + rosuvastatin;2 groups (n=62) continued the previous drug treatment. Clinical, demographic, office blood pressure (BP), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol, triglycerides, C-reactive protein (CRP) levels were assessed in all patients in 3 visits within 24 weeks. Results. The groups did not differ in prior antihypertensive therapy (except for more frequent use of angiotensin II receptor blockers in group 2, p<0.05), lipid profile and blood pressure parameters at study entry. A decrease in systolic (by 9.5%) and diastolic blood pressure (by 12.1%) after 24 weeks was found in group 1 compared with 4.29% and 5.56%, respectively, in group 2 (p<0.05). A decrease in the level of total cholesterol by 14.5% and LDL-c by 31.4% after 24 weeks was found in group 1 compared with 11.2% and 9.7%, respectively, in group 2 (p<0.05). The level of CRP during the observation period decreased by 53.7% in group 1 versus 43.4% in patients of group 2 (p<0.05). Conclusion. The single pill combination of lisinopril/amlodipine/rosuvastatin in hypertensive patients with dyslipidemia who underwent COVID-19 led to an improvement in lipid profile and blood pressure control.

7.
Avicenna Journal of Medical Biotechnology ; 14(3):233-238, 2022.
Article in English | EMBASE | ID: covidwho-1957621

ABSTRACT

Background: Evidence on seroconversion profile of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients is limited. We mainly aimed to evaluate seroconversion and persistence of virus-specific antibodies in patients infected by coronavirus disease 2019 (COVID-19). Methods: This prospective study was conducted on 118 patients with COVID-19 presen-tations admitted to three hospitals in Iran and recovered from the disease, during April and May 2020. Presence of COVID-19 was confirmed by Polymerase Chain Reaction (PCR) testing on nasopharyngeal swabs. Serum samples were collected at different time points, including 0-5, 6-15, 16-25, 26-35, and 36-95 days of clinical symptom onset. For measurement of SARS-CoV-2-specific IgG and IgM antibody titers, Iran's Food and Drug Administration-approved SARS-CoV-2 ELISA kits were used. Results: Serologic assay revealed that 37.3% of patients (n=44) were positive for IgM at 0-5 days interval after clinical symptom onset. This rate was 60.2% (n=71) for IgG. There were increasing IgM and IgG seroconversion rates during first 25 days of clinical symptom onset, but seropositivity started to decrease thereafter, which was more evi-dent for IgM (17.9%) than IgG (58.9%) at the 36-95 days post symptoms appearance. In other words, it was found that 83.6% of IgM-positive and 32.9% of IgG-positive patients in the first month of clinical symptom onset became seronegative in the third month of clinical symptom onset. Conclusion: The findings demonstrated that antibody responses to SARS-CoV-2 infection were developed in recovered COVID-19 patients;however, some of them were seronegative three months after onset of relevant symptoms. Furthermore, the stability of anti-SARS-CoV-2 antibodies could also correct our expectations from COVID-19 vaccination responses.

8.
Obstetrics, Gynecology and Reproduction ; 16(2):158-175, 2022.
Article in Russian | EMBASE | ID: covidwho-1957618

ABSTRACT

These days, anticoagulants are in great demand. They are used as a prophylaxis for thromboembolic complications in various diseases and conditions in general therapeutic practice, cardiology, neurology, as well as obstetrics to manage high-risk pregnancies. The relevance of anticoagulants competent use has come to the fore in connection with the emergence of a new disease – COVID-19 and its serious complications such as developing thrombotic storm, in which the timely applied anticoagulant therapy is the key to the success of therapy. The risk of bleeding should be considered when using any anticoagulant. Age, impaired renal function and concomitant use of antiplatelet agents are common risk factors for bleeding. Moreover, only vitamin K antagonists and heparin have specific antidotes – vitamin K and protamine, respectively. Inhibitors of other anticoagulants are universal presented as inactivated or activated prothrombin complex concentrate and recombinant factor VIIa. Hemodialysis effectively reduces dabigatran concentration, activated charcoal is effective in the case of recent oral administration of lipophilic drugs. Research on new antidotes of currently available anticoagulants is under way, similar to testing of new types of anticoagulants that are sufficiently effective in preventing and treating thromboembolic complications with minimal risk of hemorrhagic. The main contraindication to anticoagulants use is the doctor's ignorance of the mechanisms of drug action and opportunities for suppressing its effect.

9.
Biomedical Reviews ; 32:37-46, 2021.
Article in English | EMBASE | ID: covidwho-1957608

ABSTRACT

Butyrylcholinesterase (BChE), a hepatic enzyme produced by the liver is affected by and influences a variety of inflammatory, infectious and metabolic dysfunction processes. Considering that COVID-19 is a multisystem disorder related to conditions influenced by BChE, the potential interrelation of the two is reviewed. BChE is altered in a variety of infectious diseases, and serves as a prognostic marker in both infections and in non-infectious diseases. Closely related to acetylcholinesterase (AChE), BChE plays a role in modulating inflammation via the cholinergic system. It forms part of the signaling pathway linking the immune system, nervous system and the endocrine system. COVID-19 progresses to a stage of unregulated inflammation in a subset of subjects. Cholinergic dysfunction could be potentially responsible for a march to cytokine storm. BChE could influence the course of COVID-19 by acting through the brain-immune-endocrine axis via cholinergic transmission, as well as affecting factors predicting adverse outcomes of COVID-19 (obesity, insulin resistance, coronary artery disease, type 2 diabetes mellitus). Interestingly, variant forms of the enzyme with impaired hydrolytic activity are reported in endogamous ethnic populations. It would be instructive to study the effect of COVID-19 in these natural human knock-out equivalents. Biomed Rev 2021;32: 37-46.

10.
Nevrologiya, Neiropsikhiatriya, Psikhosomatika ; 14(2):91-97, 2022.
Article in Russian | EMBASE | ID: covidwho-1957599

ABSTRACT

The novel coronavirus infection is commonly referred to as COVID-19, sometimes by the name of the causative agent of a respiratory viral infection, as SARS-CoV-2. Frequently, the course of COVID-19 is divided into three main periods: acute COVID-19 (up to 4 weeks), post-acute COVID-19 (from 4 to 12 weeks), post-COVID (post-COVID;from 12 weeks to 6 months). If a more protracted course of COVID (over 6 months) is discussed, the term “long-COVID” is used. All observations demonstrated a high incidence of pain syndromes of various localization in the post-COVID period and long-COVID. According to survey data, 92.3% of patients with COVID-19 reported musculoskeletal problems at the time of admission. Pain syndrome is observed in 56.3% of cases 1 month after hospitalization. Three months after COVID-19, myalgia was observed in 40.55% of cases, joint pain in 39.18%, back pain in 31.62%, and lower back pain in 24.74%. After 6 months, joint pain continues to be observed in 18.59% of patients, myalgia - in 15.09%, back pain - in 14.39%, lower back pain - in 11.23%. In 50.8% of cases, patients reported new-onset pain, of which 38.5% had pain of moderate severity (≥3 points on the visual analog scale). Patients with new-onset pain during COVID had worse quality of life indicators and a negative correlation with the pain syndrome severity, which significantly hampered recovery. Data from a meta-analysis that included 47,910 patients with long-COVID and with a protracted course of COVID indicate that 19% of them had pain in the joints of various localization. The direct cytopathic effect of SARS-CoV-2 and the systemic immune inflammation that occurs in response to infection cause damage to the joint tissue. According to the Guidelines for the Treatment of Patients with the Consequences of COVID-19, it is recommended to use slow acting structure-modifying drugs - SYSADOA - in the pharmacological treatment regimen for patients with osteoarthritis, among which parenteral forms of pharmaceutically standardized drugs - chondroitin sulfate (CS) and glucosamine sulfate (GS) are preferred. GS and CS are inhibitors of the signaling cascade of the nuclear factor NF-κB, which is involved in the realization of biological effects of a pro-inflammatory cytokine (tumor necrosis factor α), the excessive activity of which is associated with the cytokine storm in COVID-19.

11.
Nevrologiya, Neiropsikhiatriya, Psikhosomatika ; 14(1):108-114, 2022.
Article in English | EMBASE | ID: covidwho-1957598

ABSTRACT

We present familial tuberous sclerosis (TS) case complicated by COVID-19. COVID-19 aggravates the course of TS and may lead to a fatal outcome. We review the role of mTORC1 (mechanistic/mammalian Target of Rapamycin Complex 1) in the development and functions of the nervous system and the pathogenesis of TS and COVID-19 with emphasis on the involvement of the brain and lungs. We observed that COVID-19 worsens the course of epilepsy in patients with TS. In TS patients, lymphangioleiomyomatosis may predispose to SARS-CoV-2 invasion into the respiratory system because of the increased expression of ACE2 and TMPRSS2 in type II pneumocytes and thus may worsen the prognosis. We also review the current data on the continuation/termination of everolimus administration in patients with TS associated with COVID-19.

12.
Journal of Clinical and Diagnostic Research ; 16(7):EC13-EC16, 2022.
Article in English | EMBASE | ID: covidwho-1957576

ABSTRACT

Introduction: There is inadequate information on infections with the Severe Acute Respiratory Syndrome Virus 2 (SARS-CoV-2) in children. Their clinical, as well as pathological correlation, is poorly understood. In India, children and adolescents account for 12% of all Coronavirus Disease 2019 (COVID-19) cases reported. Children accounted for roughly 11% of those impacted globally last year. However, this year, we are seeing around 20-40% of youngsters in positive instances over the world. Even babies and infants are testing positive for COVID-19, although their illness is under control and seldom becomes fatal. Children aged 5 to 12 years, on the other hand, are at a higher risk. Aim: To study the clinical, pathological and genomic characteristics among children with SARS-CoV-2 infection. Materials and Methods: This cross-sectional study was conducted among 48 paediatric positive patients for SARSCoV-2 at Government Institute of Medical Sciences, Noida, Uttar Pradesh, and CSIR-Institute of Genomics and Integrative Biology, New Delhi, India, from 2021 and May 2021. The laboratory testing was done by the real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) method. The patients were classified as mild, moderate, severe, or asymptomatic. Their clinical and pathological findings were recorded in the case sheet. Genomic analyses were done for identifying the genetic variant in the nine selected samples. Data entry and analysis were performed using Statistical Package for Social Sciences (SPSS) version 26.0. Chi-square test was used for categorical variables and the t-test was used for continuous variables. results: The study group has median age of 12 years. Male:Female ratio was 2:3. Most children had acquired infection from the community and 30% had the moderate illness and were admitted. Serum Glutamic-Oxalacetic Transaminase (SGOT) and Glutamic-Pyruvic Transaminase (SGPT) were raised in six patients. Alkaline Phosphatase (ALP) was raised in 21 patients and bilirubin was raised in two patients. The average duration of hospitalization was 6 days (range 2-13 days). No mortality among the 48 paediatric patients studied was identified in the hospital. Delta variant (B.1.617.2) was identified in seven patients with D614, P681R, L452R mutations and B.1.617.2 was identified in two patients. Delta variant was present in the paediatric patients but it did not prolong the hospital stay or cause mortality. conclusion: The findings of the study suggest that children may be a potential source of infection in the SARS CoV2 pandemic while having an asymptomatic to mild illness.

13.
Journal of Clinical and Diagnostic Research ; 16(7):NC01-NC05, 2022.
Article in English | EMBASE | ID: covidwho-1957574

ABSTRACT

Introduction: Rhino-orbito-cerebral Mucormycosis (ROCM) is an uncommon but devastating fungal infection caused by Mucoraceae family fungi, which are angiotropic and filamentous, with significantly high morbidity and mortality despite treatment. Post Coronavirus Disease-2019 (COVID-19), there was a sudden surge in ROCM cases nationwide due to immunologically and metabolically compromised status. Aim: To describe retinal manifestations in ROCM in a tertiary eye care centre of Northern India. Materials and Methods: An analytic, cross-sectional and hospital-based study was conducted in Regional Institute of Ophthalmology, PGIMS Rohtak, Haryana, India, from May 2021 to September 2021. This study was conducted on 200 admitted patients of RCOM in the institute, which was only designated Nodal centre in Haryana, India. Detailed history was recorded in every patient regarding presenting symptoms, history of COVID-19, hospital stay, oxygen inhalation, steroid intake and immunisation. Thorough ocular examination was done in every patient including visual acuity, ocular movements and pupillary reactions. Dilated fundus examination was done by Indirect Ophthalmoscopy (IDO) for posterior segment evaluation. Contrast Enhanced Magnetic Resonance Imaging (CE-MRI) brain with orbit and Paranasal Sinus (PNS) was done in every patient to see the extent of spread and planning further management. Results: Out of 200 patients of ROCM, majority of patients (64/200) were of 51-60 year age group (32%) followed by 41-50 year age group (28%). Out of 200 cases of ROCM, 146 patients (73%) had history of COVID-19 infection in past and 134 (67%) patients had history of hospital stay during COVID-19 infection. Oxygen (O2) supplementation was given to 98 patients either at home or during hospital stay. History of steroid intake was present in 34 patients and 46 patients received injection Remedsivir. Only 12 patients had vaccine against COVID-19 and none of them were fully vaccinated. Most common presenting symptom was unilateral nasal stiffness (22%) followed by loss of vision (17%). Most common predisposing factor was Diabetes Mellitus (DM) in 78 patients (39%) followed by steroid intake in 34 patients (17%). Out of 200 patients, only 60 patients had retinal manifestations and most common was Central Retinal Artery Occlusion (CRAO) (35/60) and the main mechanism is the direct infiltration of central retinal artery due to angioinvasion of fungi from the orbit. Conclusion: CE-MRI brain with orbit is an important tool in diagnosing and monitoring progression of RCOM but it cannot provide information regarding retinal findings like CRAO, central retinal venous occlusion (CRVO), disc pallor and optic atrophy. Thus, the fundus examination of every ROCM patient should be emphasised, as it not only helps in categorising ROCM but also tells about the visual potential of affected eye. Patients with CRAO and combined vascular occlusion should be considered for exenteration on urgent basis, so that intracranial spread can be prevented and patient's life can be saved.

14.
Pharmacognosy Journal ; 14(3):604-609, 2022.
Article in English | EMBASE | ID: covidwho-1957552

ABSTRACT

The global pandemic of coronavirus disease is still widely spread across the world causing catastrophic effect in both human life and global economy. By the end of year 2021, it has caused a total of 5.437.636 deaths across the world. Indonesia has rich plant biodiversity including medicinal plants that may be used for combating the virus. One of the commonly used medicinal plants comes from Allium species and it has been proved to have antiviral activity. Conducting an in silico study, we screened bioactive compounds that came from Allium sativum to fight against coronavirus through the inhibition of 3CL-Pro, one of the major protease that have an active role for viral replication. Molecular docking of compounds from Allium sativum to 3CL-Pro resulting in the discovery of 5 compounds that have the best binding affinity to 3CL-Pro, which are squalene, 1,4-dihydro-2,3-benzoxathiin 3-oxide, 1,2,3-propanetriyl ester, trans-13-octadecenoic acid and methyl-11-hexadecenoate with binding affinity of -7, -6.5, -5.9, -5.7 and -5.6 kcal/mol, respectively. It is very likely that these compounds can be candidates for therapeutic agents and these candidates need to be studied further.

15.
Pharmacognosy Journal ; 14(3):591-597, 2022.
Article in English | EMBASE | ID: covidwho-1957551

ABSTRACT

Currently, Canine coronavirus (CCoV) is an enteric pathogen of the Alphacoronavirus-1 species that causes mild to severe diarrhea in puppies. The pathogenesis of this infection will cause severe lymphopenia and lead to death in puppies. This study aimed to determine the administration of probiotics on TNF-α expression, histological findings of the liver and lung in mice infected with CCoV. A total of 28 mice were randomly assigned into seven treatment groups, i.e. (C-) placebo;(C+) active CCoV vaccine induction;(T1) CCov + Isopronosin;(T2) CCoV + Lactobacillus acidophilus probiotic;(T3) CCoV + Lactobacillus Acidophylus and Bifidobacterium probiotics;(T4) CCoV + colustrum fermentation probiotic;(T5) CCoV + ginger, turmeric and ginger probiotics. Thereafter, the expression of TNF-α in the duodenum was stained using immunohistochemistry, liver and lung were stained using hematoxylin eosin. The data were analyzed using the ANOVA test followed by the Tukey test with a significance level (p<0.05). TNF-α expression on T4 and T5 decreased significantly (p<0.05) compared to C+, T1, T2 and T3. Histologic findings of the liver in the C- and T4 groups showed normal features in the central vein. On the other hand, glycogen accumulation was found in hepatocyte cells, hemorrhage with sinusoid dilation, lymphocyte infiltration in centro lobular area in group C+. Lung histology showed normal features of sinusoids and alveolar septa in groups C- and T4. Meanwhile, intra-alveolar hemorrhage was found with neutrophil cell infiltration and fibrin plasma accumulation in group C+. In conclusion, colostrum fermentation probiotics can reduce TNF-α expression in the duodenum and improve the liver and lung physiology in mice infected with CCoV.

16.
Journal of Research in Medical Sciences ; 27(1):43, 2022.
Article in English | EMBASE | ID: covidwho-1957520

ABSTRACT

Background: Since December 2019, the world is struggling with an outbreak of coronavirus disease-2019 (COVID-19) infection mostly represented as an acute respiratory distress syndrome and has turned into the most critical health issue worldwide. Limited information is available about the association between dynamic changes in the naso/oropharyngeal viral shedding in infected patients and biomarkers, aiming to be assessed in the current study. Materials and Methods: This quasi-cohort study was conducted on 31 patients with moderate severity of COVID-19 manifestations, whose real-time polymerase chain reaction (RT-PCR) test was positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) RNA at baseline. RT-PCR was rechecked for patients every 3-4 days until achieving two negative ones. In parallel, biomarkers, including lymphocyte count, lactate dehydrogenase (LDH), and C-reactive protein (CRP), were assessed every other day, as well. Viral shedding also was assessed. Results: Spearman's correlation test revealed a significant direct correlation between the viral shedding from the symptom onset and the time, in which CRP (P = 0.0015, r = 0.54) and LDH (P = 0.001, r = 0.6207) return to normal levels after symptom onset, but not for lymphocyte count (P = 0.068, r = 0.34). Conclusion: Based on the current study's findings, the duration of SARS-CoV-2 RNA shedding was directly correlated with the required time for LDH and CRP return to normal levels. Therefore, these factors can be considered the determinants for patients' discharge, isolation, and return to social activities;however, further investigations are required to generalize the outcomes.

17.
International Journal of Pharmacology ; 18(5):1079-1083, 2022.
Article in English | EMBASE | ID: covidwho-1957491

ABSTRACT

Background and Objective: The fungal infection, caused by the newly discovered highly resistant Candida auris was a major health threat before COVID-19. The concept of drug repurposing not only addresses the issue of microbial resistance, but also is an easy way to bypass costly and time-consuming novel drug development. Rationale: Statins which are therapeutically used for the treatment of atherosclerosis, have exhibited some antifungal actions against various fungal spp. Although, no such study was conducted on C. auris. Based on the anti-HMG-CoA reductase activity on ergosterol synthesis, we elucidated the effect of Atorvastatin at the clinically administered human dose (0.055g), on Candida auris. Materials and Methods: Candida auris was isolated from an adult male diabetic patient and was identified on the VITEK system and confirmed on MALDI-TOF MS with 99% accuracy. It was cultured on 24 g potato Dextrose Agar (PDA). Pure atorvastatin was incorporated in culture plates, incubated at 37∘C observed for fungal growth. Results: Initially no growth was observed in the first twenty-four hours, but an unexpected growth was observed after 48 hours, and the colonization further doubled in 96 hours. Conclusion: Atorvastatin was repurposed in C. auris due to its anti-HMGCoA reductase activity on ergosterol synthesis. The observation raises cautions among the patients on atorvastatin therapy at the clinically administered human dose (0.055 g), on a clinical isolate of C. auris isolate. Our investigation provides an awareness that the patients on a statin-therapy should be highly cautious about C. auris infection and must take appropriate measures to prevent the infection.

18.
Drug Delivery Letters ; 12(1):54-61, 2022.
Article in English | EMBASE | ID: covidwho-1957135

ABSTRACT

Background: The COVID-19 pandemic emerged at the end of 2019 in China and spread rapidly all over the world. Scientists strive to find virus-specific antivirals against COVID-19 disease. This study aimed to assess bioactive coumarinolignans (Aquillochin, Grewin) as potential SARS-CoV-2 main protease (SARS-CoV-2 Mpro) inhibitors using a molecular docking study. Methods: The detailed interactions between coumarinolignans and SARS-CoV-2 Mpro were determined as hydrophobic bonds, hydrogen bonds, electronic bonds, inhibition activity, ligand efficiency, bonding type, and distance using Autodock 4.2 software. SARS-CoV-2 Mpro was docked with Aquillochin and Grewin, and the docking results were analyzed by Autodock 4.2 and Biovia Discovery Studio 4.5. Nelfinavir and Lopinavir were used as standards for comparison. Results: The binding energies of the SARS-CoV-2 Mpro-coumarinolignan’s complexes were identified from the molecular docking of SARS-CoV-2 Mpro. Aquillochin and Grewin were found to be-7.5 and-8.4 kcal/mol, respectively. The binding sites of the coumarinolignans to SARS-CoV-2 Mpro were identified with the main interactions being π-alkyl, alkyl, π-cation, π-π T-Shaped, and hydrogen bonding. Furthermore, SwissADME web tools were used to evaluate ADMET properties and pharmacokinetic parameters of Aquillochin and Grewin. The results of ADMET and pharmacokinetic results of the Aquillochin and Grewin showed that these coumarinolignans were consonant with the many accepted rules and the criteria of drug-likeness. Conclusion: Aquillochin and Grewin obey Lipinski’s rule of five. According to the results obtained from molecular docking studies and ADMET predictions, Aquillochin and Grewin have shown weak efficacy as drug candidates against COVID-19 disease.

19.
Letters in Drug Design and Discovery ; 19(8):741-756, 2022.
Article in English | EMBASE | ID: covidwho-1957133

ABSTRACT

Background: Coronavirus disease-2019 (COVID-19) has recently emerged as a pandemic respiratory disease with mild to severe pneumonia symptoms. No clinical antiviral agent is available so far. However, several repurposing drugs and vaccines are being given to individuals or in clinical trials against SARS-CoV-2 Objective: The aim of this study is to uncover the potential effects of Luteolin (Lut) as an inhibitor of SARS-CoV2 encoded proteins via utilizing computational tools. Methods: Molecular modelling to unfold the anti-SARS-CoV2 potential of Lut along with reference drugs namely remdesivir and nafamostat was performed by the use of molecular docking, molecular dynamic (MD) simulation, absorption, distribution, metabolism, excretion, toxicity (ADMET) and density functional theory (DFT) methods against the five different SARS-CoV-2 encoded key proteins and one human receptor protein. The chemical reactivity of Luteolin is done through prediction of HOMO-LUMO gap energy and other chemical descriptors analysis. Results: In the present study, Lut binds effectively in the binding pockets of spike glycoprotein (6VSB), ADP phosphatase of NSP3 (6W02), and RNA dependent RNA polymerase (7AAP) protein receptors with significant values of docking scores-7.00,-7.25, and-6.46 respectively as compared to reference drugs remdesivir and nafamostat. Conclusion: Thus, Lut can act as a therapeutic agent and is orally safe for human consumption as predicted by molecular modelling against SARS-CoV-2 in the treatment of COVID-19.

20.
Natural Product Communications ; 17(7), 2022.
Article in English | EMBASE | ID: covidwho-1956964

ABSTRACT

Objective: The Chinese herbal formula Huo-Xiang-Zheng-Qi (HXZQ) is effective in preventing and treating coronavirus disease 19 (COVID-19) infection;however, its mechanism remains unclear. This study used network pharmacology and molecular docking techniques to investigate the mechanism of action of HXZQ in preventing and treating COVID-19. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to search for the active ingredients and targets of the 10 traditional Chinese medicines (TCMs) of HXZQ prescription (HXZQP). GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledge Base (PharmGKB), Therapeutic Target Database (TTD), and DrugBank databases were used to screen COVID-19-related genes and intersect them with the targets of HXZQP to obtain the drug efficacy targets. Cytoscape 3.8 software was used to construct the drug-active ingredient–target interaction network of HXZQP and perform protein–protein interaction (PPI) network construction and topology analysis. R software was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, AutoDock Vina was utilized for molecular docking of the active ingredients of TCM and drug target proteins. Results: A total of 151 active ingredients and 250 HXZQP targets were identified. Among these, 136 active ingredients and 67 targets of HXZQP were found to be involved in the prevention and treatment of COVID-19. The core proteins identified in the PPI network were MAPK1, MAPK3, MAPK8, MAPK14, STAT3, and PTGS2. Using GO and KEGG pathway enrichment analysis, HXZQP was found to primarily participate in biological processes such as defense response to a virus, cellular response to biotic stimulus, response to lipopolysaccharide, PI3K-Akt signaling pathway, Th17 cell differentiation, HIF-1 signaling pathway, and other signaling pathways closely related to COVID-19. Molecular docking results reflected that the active ingredients of HXZQP have a reliable affinity toward EGFR, MAPK1, MAPK3, MAPK8, and STAT3 proteins. Conclusion: Our study elucidated the main targets and pathways of HXZQP in the prevention and treatment of COVID-19. The study findings provide a basis for further investigation of the pharmacological effects of HXZQP.

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