scholarly journals Study of Naturally-derived Biomolecules as Therapeutics against SARS-CoV-2 Viral Spike Protein

2021 ◽  
pp. 211-220
Author(s):  
Pitambar Khanal ◽  
Udeep Chawla ◽  
Shagufta Praveen ◽  
Zeenat Malik ◽  
Sheeba Malik ◽  
...  
Keyword(s):  
Side Effects ◽  
Binding Affinity ◽  
Bioactive Compounds ◽  
Safety Profile ◽  
Binding Free Energy ◽  
Antiviral Agents ◽  
Computational Prediction ◽  
Spike Protein ◽  
Co Morbidity

The SARS-CoV2 virus, the causative agent for COVID-19 disease has to lead to more than 3.1 million deaths and crossed 146 million infections worldwide so far. Although vaccines development and emergency authorization has been approved by several governments, there has been great concern about its side effects for the long term and its effectiveness against new mutated strains. A resurgence of COVID-19 or related disease can be catastrophic. There is an urgent need to look for effective antiviral agents for many coronavirus strains with minimum side-effects, and maximum efficacy globally. Several, naturally-derived biomolecules have proved their excellent effect on several infectious diseases in a multi-mode fashion by targeting several pathways as well as increasing efficacy with high safety profile. Integrate computational prediction design was used in the study to examine the pharmacology of bioactive compounds of natural origin against SARS-CoV2 spike protein. Keeping these facts we have computationally examined 16 naturally occurring compounds using to evaluate their effectiveness against the SARS-CoV2 virus using the molecular docking technique. Hesperidin derivatives are known to ameliorate diabetes, co-morbidity for coronavirus, as well as help in preventing post coronavirus complications. We found the binding free energy of Hesperidin with spike protein to be -7.57 kcal/mol, the aglycone derivative to be -6.93 kcal/mol, hesperidin monoacetyl derivative to be -7.82 kcal/mol, and hesperidin pentaacetyl derivative to be -8.39 kcal/mol. Our findings revealed that acetylated derivatives of hesperidin showed significant improved remarked binding affinity while aglycone derivative hesperetin showed a decrease in binding affinity. Our studies give a new direction where natural bioactive compounds and their derivatives can be modulated and used after clinical trials to effectively inhibit coronavirus infection as well as diabetes simultaneously with a high safety profile.   Graphical Abstract

scholarly journals Dual orexin receptor antagonist in treatment of insomnia

Engrami ◽  
2020 ◽  
Vol 42 (2) ◽  
pp. 57-68
Author(s):  
Nikola Trajanović
Keyword(s):  
Circadian Rhythm ◽  
Side Effects ◽  
Receptor Antagonist ◽  
Safety Profile ◽  
The Elderly ◽  
First Line ◽  
Future Studies ◽  
Good Safety Profile ◽  
Circadian Rhythm Disorders

A novel group of medications, dual orexin receptor antagonists, emerged as a competent group that challenges current first-line hypnotics. They have relatively infrequent and mostly well-tolerated side effects, primarily in the form of residual somnolence, fatigue and nightmares/disturbing dreams. The advantage over conventional hypnotics stems from the specifics of their target receptors, which translates into lack of tolerance after long term use and good safety profile. They are particularly favoured in some specific populations, including the elderly. Ongoing and future studies are set to explore their effect on selected conditions, such as addiction and psychiatric disorders, dementias, perimenopausal condition and circadian rhythm disorders, to name a few.

scholarly journals Safety, Efficacy, and Patient Acceptability of Montelukast in Exercise-Induced Asthma

2012 ◽  
Vol 4 ◽  
pp. CMT.S7389
Author(s):  
S. Kansra ◽  
A. Mazzei ◽  
J. Bhatt
Keyword(s):  
Abdominal Pain ◽  
Individual Differences ◽  
Side Effects ◽  
Safety Profile ◽  
Leukotriene Receptor Antagonist ◽  
Patient Acceptability ◽  
Asthmatic Children ◽  
Leukotriene Receptor ◽  
Exercise Induced

Exercise-induced bronchoconstriction (EIB) can be a troublesome problem in asthmatic children and in some children without asthma. Self-reported exercise related symptoms should be verified formally. EIB is mediated by changes in temperature and humidity in the airway and is secondary to release of several mediators of the bronchoconstriction including leukotrienes. Montelukast as a leukotriene receptor antagonist offers protection against but does not completely ameliorate EIB. Regular use does not appear to lead to tolerance. Nightmares, abdominal pain, fever, nausea and aggressiveness are commonly described side effects; however, the overall safety profile of montelukast is good and does not change with long term use. There are individual differences in response to montelukast for protection against EIB. Bronchoconstriction triggered by exercise responds to cessation of exercise in its natural course. Due to its pharamacokinetic profile, montelukast may be more useful as a prophylaxis than to relieve symptoms.

scholarly journals Molecular simulation of SARS-CoV-2 spike protein binding to pangolin ACE2 or human ACE2 natural variants reveals altered susceptibility to infection

2020 ◽  
Vol 101 (9) ◽  
pp. 921-924 ◽  
Author(s):  
Jingfang Wang ◽  
Xintian Xu ◽  
Xinbo Zhou ◽  
Ping Chen ◽  
Huiying Liang ◽  
...  
Keyword(s):  
Free Energy ◽  
Protein Binding ◽  
Binding Affinity ◽  
Binding Free Energy ◽  
Virus Transmission ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Susceptibility To Infection ◽  
Natural Variants ◽  
Complex Models

We constructed complex models of SARS-CoV-2 spike protein binding to pangolin or human ACE2, the receptor for virus transmission, and estimated the binding free energy changes using molecular dynamics simulation. SARS-CoV-2 can bind to both pangolin and human ACE2, but has a significantly lower binding affinity for pangolin ACE2 due to the increased binding free energy (9.5 kcal mol−1). Human ACE2 is among the most polymorphous genes, for which we identified 317 missense single-nucleotide variations (SNVs) from the dbSNP database. Three SNVs, E329G (rs143936283), M82I (rs267606406) and K26R (rs4646116), had a significant reduction in binding free energy, which indicated higher binding affinity than wild-type ACE2 and greater susceptibility to SARS-CoV-2 infection for people with them. Three other SNVs, D355N (rs961360700), E37K (rs146676783) and I21T (rs1244687367), had a significant increase in binding free energy, which indicated lower binding affinity and reduced susceptibility to SARS-CoV-2 infection.

scholarly journals Lipodystrophy of Abdominal Pannus: A Severe Complication of Phosphatidyl Choline Injections

2021 ◽  
Author(s):  
Parag S. Telang
Keyword(s):  
Side Effects ◽  
Surgical Management ◽  
Safety Profile ◽  
Phosphatidyl Choline ◽  
Subcutaneous Fat ◽  
Severe Complication ◽  
Acceptable Result ◽  
Injection Lipolysis

Abstract“Injection lipolysis” or “mesotherapy” is done for introducing various substances into deeper layers of the skin with the aim to dissolve subcutaneous fat. However, the safety profile of these chemicals is poorly regulated. Therefore, they may cause side effects or long-term sequelae that can be disastrous for the patient. We present such a case that required surgical management to salvage it and to give an aesthetically acceptable result.

scholarly journals COVID-19 Vaccines: A Review of the Safety and Efficacy of Current Clinical Trials

2021 ◽  
Vol 14 (5) ◽  
pp. 406
Author(s):  
Zhi-Peng Yan ◽  
Ming Yang ◽  
Ching-Lung Lai
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Safety Profile ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Herd Immunity ◽  
Short Term ◽  
Safety And Efficacy ◽  
Protection Time

Various strategies have been designed to contain the COVID-19 pandemic. Among them, vaccine development is high on the agenda in spite of the unknown duration of the protection time. Various vaccines have been under clinical trials with promising results in different countries. The protective efficacy and the short-term and long-term side effects of the vaccines are of major concern. Therefore, comparing the protective efficacy and risks of vaccination is essential for the global control of COVID-19 through herd immunity. This study reviews the most recent data of 12 vaccines to evaluate their efficacy, safety profile and usage in various populations.

scholarly journals High risk of cardiovascular side effects after treatment of Hodgkin’s lymphoma – is there a need for intervention in long-term survivors?

2021 ◽  
Vol 126 (1) ◽  
Author(s):  
Anne Andersson ◽  
Beatrice Melin ◽  
Gunilla Enblad ◽  
Martin Erlanson ◽  
Ann-Sofie Johansson ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Side Effects ◽  
Hodgkin Lymphoma ◽  
Clinical Symptoms ◽  
Medical Community ◽  
Adequate Treatment ◽  
Cardiac Symptoms ◽  
Cardiovascular Side Effects ◽  
Co Morbidity

Background: Hodgkin lymphoma (HL) patients have a good prognosis after adequate treatment. Previous treatment with mantle field irradiation has been accompanied by an increased long-term risk of cardiovascular disease (CVD). This study identified co-morbidity factors for the development of cardiovascular side effects and initiated an intervention study aimed to decrease morbidity and mortality of CVD in HL survivors. Design: Hodgkin lymphoma patients aged ≤45 years diagnosed between 1965 and 1995 were invited to participate. In total, 453 patients completed a questionnaire that addressed co-morbidity factors and clinical symptoms. Of these, 319 accepted to participate in a structured clinical visit. The statistical analyses compared individuals with CVD with those with no CVD. Results: Cardiovascular disease was reported by 27.9%. Radiotherapy (odds ratio [OR]: 3.27), hypertension and hypercholesterolemia were shown to be independent risk factors for the development of CVD. The OR for CVD and valve disease in patients who received radiotherapy towards mediastinum was 4.48 and 6.07, respectively. At clinical visits, 42% of the patients were referred for further investigation and 24% of these had a cardiac ultrasound performed due to previously unknown heart murmurs. Conclusion: Radiotherapy towards mediastinum was an independent risk factor for CVD as well as hypercholesterolemia and hypertension. A reasonable approach as intervention for this cohort of patients is regular monitoring of hypertension and hypercholesterolemia and referral to adequate investigation when cardiac symptoms appear. Broad knowledge about the side effects from radiotherapy in the medical community and well-structured information regarding late side effects to the patients are all reasonable approaches as late effects can occur even 40 years after cancer treatment.

scholarly journals Predicting the Potential Effect of E484K Mutation on the Binding of 28 Antibodies to the Spike Protein of SARS-CoV-2 by Molecular Dynamics Simulation and Free Energy Calculation

2021 ◽  
Author(s):  
Leyun Wu ◽  
Cheng Peng ◽  
Zhijian Xu ◽  
weiliang zhu
Keyword(s):  
Free Energy ◽  
Binding Affinity ◽  
Immune Escape ◽  
Binding Free Energy ◽  
Experimental Studies ◽  
Potential Effect ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Energy Calculation ◽  
Potential Impact

Vaccines and antibody therapeutic are needed to fight the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has spread since 2020. Experimental studies have shown that the E484K variant may escape the neutralization of antibodies. To explore the potential impact of E484K mutation on the antibody binding affinity, we calculated the binding free energy of 28 antibodies to the wild type and K484 mutant of the spike protein of SARS-CoV-2. We found that 71% of the antibodies show lower binding affinity to the E484K mutant, indicating the highly possible immune escape risk of the mutated virus. Further analysis revealed that the other mutations, e.g. F490 and V483, are also likely to cause immune escape.

scholarly journals Investigation of the Frequency of Adverse Effects in Patients Treated with Favipiravir as SARS-CoV-2 Treatment

2021 ◽  
pp. 1-4
Author(s):  
Ebru Dogan ◽  
Sevil Alkan Çeviker ◽  
Servan Vurucu ◽  
Alper Sener ◽  
Buse Yuksel ◽  
...  
Keyword(s):  
Side Effects ◽  
Demographic Data ◽  
Antiviral Agents ◽  
Good Alternative ◽  
Long Term Effects ◽  
Cardiac Side Effects ◽  
Significant Difference ◽  
Gastrointestinal Side Effects ◽  
Treatment Agent

Objective: For 2019 and 2020, SARS-CoV-2 has been a sensational virus. Unfortunately, a treatment agent specific for SARS-CoV-2 has not been developed yet. Favipiravir is one of the antiviral agents used experimentally in the treatment of SARS-CoV-2. This study aimed to determine the frequency of side effects seen in patients hospitalized in our hospital and received favipiravir at any stage of their treatment. Methods: Our study is a retrospective observational study. Definite and probable COVID-19 cases hospitalized in our hospital between March 23, 2020, May 31, 2020, were determined, and those receiving favipiravir as initial or secondary therapy were included in the study. The demographic data, laboratory tests, observed side effects of the patients were recorded and analyzed statistically. Results: A total of 134 patients, 37.3% using favipiravir at the beginning and 62.7% as secondary, were included in the study. The mean age of the patients was 66.8±15.7 years. 38.1% (n=51) of the group were female. Side effects were detected in 17 (13%) patients in the whole group. Hepatotoxicity (4.5%), increased serum uric acid (4.5%), nephrotoxicity (1.5%), gastrointestinal side effects (1.5%), cardiac side effects (0.7%) were detected. There was no statistically significant difference in terms of adverse events between the patients who received favipiravir initially or later on disease course. Conclusions: Although some results support the short-term safety of favipiravir, more studies are needed for its long-term effects. Studies on hyperuricemia, QTc prolongation, use in pregnancy, use during lactation and use in children are insufficient. Therefore, although Favipiravir appears to be a good alternative in the treatment of COVID-19, it should be used carefully because the data on its safety is still insufficient.

scholarly journals Predicting the Potential Effect of E484K Mutation on the Binding of 28 Antibodies to the Spike Protein of SARS-CoV-2 by Molecular Dynamics Simulation and Free Energy Calculation

2021 ◽  
Author(s):  
Leyun Wu ◽  
Cheng Peng ◽  
Zhijian Xu ◽  
weiliang zhu
Keyword(s):  
Free Energy ◽  
Binding Affinity ◽  
Immune Escape ◽  
Binding Free Energy ◽  
Experimental Studies ◽  
Potential Effect ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Energy Calculation ◽  
Potential Impact

Vaccines and antibody therapeutic are needed to fight the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has spread since 2020. Experimental studies have shown that the E484K variant may escape the neutralization of antibodies. To explore the potential impact of E484K mutation on the antibody binding affinity, we calculated the binding free energy of 28 antibodies to the wild type and K484 mutant of the spike protein of SARS-CoV-2. We found that 71% of the antibodies show lower binding affinity to the E484K mutant, indicating the highly possible immune escape risk of the mutated virus. Further analysis revealed that the other mutations, e.g. F490 and V483, are also likely to cause immune escape.

scholarly journals Bilastine as a modern antihistamine for the treatment of allergic rhinitis and urticaria

2020 ◽  
Vol 17 (1) ◽  
pp. 93-100
Author(s):  
Igor S Gushchin ◽  
Ekaterina N Medunitsyn
Keyword(s):  
Allergic Rhinitis ◽  
Side Effects ◽  
Safety Profile ◽  
Clinical Studies ◽  
Second Generation ◽  
High Efficiency ◽  
Fold Increase ◽  
Term Therapy ◽  
H1 Antihistamines

Antihistamines have long been an integral part of the treatment of allergic rhinitis and urticaria. Treatment of these diseases is usually long-term, so the drugs of choice are H1-antihistamines of the second generation, which have high efficiency and a good safety profile in the absence of clinically significant side effects. The variety of drugs in this group makes it possible to personalize the therapy, using the drug taking into account the individual sensitivity of the patient. One of the antihistamines used in practical allergy at the present time is bilastine. The article presents the data of clinical studies devoted to the research of the effectiveness, safety and tolerability of Hj-antihistamine of the second generation - bilastine. Short-term and long-term use of bilastine in patients with rhinitis (rhinoconjunctivitis) and chronic urticaria has demonstrated it’s good effectiveness and safety, which are due to the pharmacological properties of the medicine and the peculiarities of its metabolism. A number of sources provide data on the high safety profile of bilastine not only in the standard therapeutic dosage, but also with its four-fold increase. The results of these studies are of particular importance, since the clinical recommendations for the management of urticaria in various countries, including Russia, provide for the possibility of increasing the dose of H1 -antihistamines in case of insufficient effectiveness of therapy. Studies have also shown that bilastine has no clinically pronounced side effects that could significantly limit the use of the medicine, including in patients with concomitant diseases, or negatively affect patient’s compliance. According to the results of clinical studies, bilastine is characterized as an effective, safe, well-tolerated medicine for long-term therapy of allergic rhinitis and urticaria.

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