Treatment Of SARS-CoV2 Research Articles

An in silico Drug Repurposing Study to Inhibit the Spike Protein of SARS-CoV2

SARS-CoV2 has caused the recent mortal pandemic known as COVID-19. The drug repurposing approach can be employed to find the potential drugs capable of binding SARS-CoV2 structural and nonstructural proteins. The present study aimed to repurpose some common FAD-approved antiviral and non-antiviral drugs computationally for SARS-CoV2 treatment. In the in silico study, 89 FDA-approved drugs and Remdesivir, as the control, were analyzed by molecular docking to inhibit the SARS-CoV2 spike (S) protein as the key player in virus-cell binding. First, the Uniport website was used to find receptor and ganglioside binding domains (RBD and GBD, respectively) of the S protein as the target. The structure of the target was downloaded from RCSB, and 'the ligands' structures were downloaded from PubChem. All structures were refined using SPDV and PyRx software. AutoDock Vina was employed for the docking process. The result showed that 8 drugs, including Ledipasvir, Montelukast, Domperidone, Aprepitant, Folic acid, Losartan, Ticagrelor, and Rivaroxaban, can bind S protein and then inhibit the protein function. In addition, Ledipasvir, Montelukast, and Domperidone can bind GBD of the S protein with higher binding energy (-8.2, -8, -7.9 kcal/mol, respectively). On the other hand, higher RBD binding energy was calculated for Ticagrelor (-6.9 kcal/mol), Folic acid, Montelukast, and Domperidone (-6.5 kcal/mol). Generally, the ligands could inhibit GBD more than RBD. According to the binding energy to S protein and low side effects of the studied medications, Ledipasvir and Losartan can be introduced as the most effective candidates for repurposed drugs. Also, Gly496 and Asn137 are the most engaged amino acids in the ligand-receptor interaction from RBD and GBD, respectively.

THE METABOLISM OF LUFOTRELVIR, A PRODRUG INVESTIGATED FOR THE TREATMENT OF SARS-COV-2, IN HUMANS FOLLOWING INTRAVENOUS ADMINISTRATION.

The metabolism of lufotrelvir, a novel phosphate prodrug of PF-00835231 for the treatment of COVID-19, was evaluated in healthy human volunteers and clinical trial participants with COVID-19 following intravenous infusion. The prodrug was completely converted to PF-00835231 which was subsequently cleared by hydrolysis, hydroxylation, ketoreduction, epimerization, renal clearance, and secretion into the feces. The main circulating metabolite was a hydrolysis product (M7) which was present at concentrations greater than PF-00835231, and this was consistent between healthy volunteers and participants with COVID-19. Upon administration of [14C]lufotrelvir, only 63% of the dose was obtained in excreta over 10 days and total drug-related material demonstrated a prolonged terminal phase half-life in plasma. A considerable portion of the labelled material was unextractable from fecal homogenate and plasma. The position of the carbon-14 atom in the labelled material was at a leucine carbonyl, and pronase digestion of the pellet derived from extraction of the fecal homogenate showed that [14C]leucine was released. Significance Statement Lufotrelvir is an experimental phosphate prodrug intravenous therapy investigated for the potential treatment of COVID-19 in a hospital setting. The overall metabolism of lufotrelvir was determined in human healthy volunteers and clinical trial participants with COVID-19. Conversion of the phosphate prodrug to the active drug PF-00835231 was complete and the subsequent metabolic clearance of the active drug was largely via amide bond hydrolysis. Substantial drug-related material was not recovered due to loss of the carbon-14 label to endogenous metabolism.

The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2

BackgroundSince the beginning of SARS-CoV2 pandemic, the mortality rate among elderly patients (60–90 years) has been around 50%, so age has been a determining factor of a worse COVID-19 prognosis. Associated with age, the thymic function involution and depletion plays an important role, that could be related to a dysregulated and ineffective innate and adaptive immune response against SARS-CoV2. Our study aims to further in vitro effect of human Thymosin-alpha-1 (α1Thy) treatment on the immune system in population groups with different thymic function levels in the scenario of SARS-CoV2 infection.ResultsActivation markers such as CD40, CD80 and TIM-3 were upregulated in α1Thy presence, especially in plasmacytoid dendritic cells (pDCs) and, with increased TNFα production was observed compared to untreated condition. Co-cultures of CD4 + and CD8 + T cells with DCs treated with α1Thy in response to SARS-CoV2 peptides showed a decrease in the cytokine production compared to the condition without α1Thy pre-treated. A decrease in CD40L activation co-receptor expression in CD8 + LTs was also observed, as well as an increase in PD1 in CD4 + TLs expression in both age groups. In fact, there are no age-related differences in the immunomodulatory effect of the hormone, and it seems that effector memory and terminally differentiated memory T lymphocyte subsets were the most actively influenced by the immunomodulatory α1Thy effect. Finally, the polyfunctionality measured in SARS-CoV2 Specific-T cells response was maintained in α1Thy presence in total and memory subpopulations CD4 + and CD8 + T-cells, despite decreased proinflammatory cytokines production.ConclusionThe hormone α1Thy could reduce, through the modulation of DCs, the amount of proinflammatory cytokines produced by T cells. Moreover, α1Thy improve lymphocyte functionality and could become a beneficial therapeutic alternative as an adjuvant in SARS-CoV2 treatment either in the acute phase after infection or reinfection. In addition, the effect on the T immune response means that α1Thy can be incorporated into the vaccination regimen, especially in the most immunologically vulnerable individuals such as the elderly.SubjectsThymosin alpha 1, Dendritic cells, SARS-CoV2-specific T cells response, Immunomodulation

Self-medication in the Bahian population during the Covid-19 pandemic period

Objective: To analyze the prevalence and possible factors associated with self-medication in the population of Bahia during the pandemic caused by Covid-19. Methods: This is an exploratory research that has a descriptive character, with a quantitative nature and approach. The research universe was composed of residents of the State of Bahia. The study was approved by the Research Ethics Committee (CEP) under protocol 4.941.863. The collected information was tabulated using Microsoft Office Excel® and the statistical analysis was carried out in a descriptive, univariate way using the Statiscal Package For Social Science (SPSS) software. Results: There were five hundred and thirty participants in this research. Among the medications contained in the questionnaire, the most used was Vitamin D, being used by 41.7% of respondents. Among the reasons for using the drug, the most prevalent was Cold/Flu with 18.4%, followed by regular consumption as cause (18.0%). Conclusion: More studies need to be carried out to confirm the effectiveness of the drugs both as prophylaxis and for the treatment of SARSCoV-2 to avoid the dissemination of information without scientific basis.

Cardiopulmonary and hematological effects of infrared LED photobiomodulation in the treatment of SARS-COV2.

COVID-19 disease is caused by SARS-CoV-2 which can trigger acute respiratory syndrome, which presents with dense alveolar and interstitial infiltrates and pulmonary edema, causing severe hypoxemia and significant alteration to pulmonary mechanics with reduced pulmonary compliance. The photobiomodulation technique alters cellular and molecular metabolism, showing promising results regarding the reduction of acute pulmonary inflammation. To compare the photomodulation technique using near-infrared LED to conventional respiratory physiotherapy treatment in patients with COVID-19 in reversing acute conditions, reducing hospitalization time, and decreasing the need for oxygen therapy. The cohort was comprised of 30 patients undergoing COVID-19 treatment who were divided and allocated into two equal groups randomly: the LED group (LED), treated with infrared LED at 940nm and conventional therapy, and the control group (CON), who received conventional treatment (antibiotic therapy for preventing superimposed bacterial infections, and physiotherapy) with LED irradiation off. Phototherapy used a vest with an array of 300 LEDs (940nm) mounted on a 36cm×58cm area and positioned in the patient's anterior thoracic and abdominal regions. The total power was 6W, with 15min irradiation time. Cardiopulmonary functions and blood count were monitored before and after treatment. The patients were treated daily for 7days. Statistical analysis was conducted using a two-tailed unpaired Student's t-test at a significance level of α=0.05. Post-treatment, the LED group showed a reduction in hospital discharge time and a statistically significant improvement for the following cardiopulmonary functions: Partial Oxygen Saturation, Tidal Volume, Maximum Inspiratory, and Expiratory Pressures, Respiratory Frequency, Heart Rate, and Systolic Blood Pressure (p<0.05). Regarding blood count, it was observed that post-treatment, the LED group presented with significant differences in the count of leukocytes, neutrophils, and lymphocytes. Photobiomodulation therapy can be used as a complement to conventional treatment of COVID-19, promoting the improvement of cardiopulmonary functions, and minimization of respiratory symptoms.

Turkish Thoracic Society Early Career Members Task Force Group's Virtual Congress Notes: European Respiratory Society International Congress 2020.

In this article, Early Career Task Force Group members of the Turkish Thoracic Society summarize the European Respiratory Society 2020 virtual congress. Current developments in the field of respiratory diseases were compiled with the addition of sessions specific to coronavirus disease 2019 this year. Almost all of the congress sessions were examined, and the important and striking results of the congress were highlighted. Congress sessions were attended by expert researchers, and the prominent messages of each session were highlighted in short summaries. They were then grouped under relevant titles and ranked in order of meaning and relation. It was finalized by a team of researchers.

Cardiopulmonary and Hematological Effects of Infrared Led Photobiomodulation in the Treatment of Sars-Cov2

Cardiopulmonary and Hematological Effects of Infrared Led Photobiomodulation in the Treatment of Sars-Cov2

First-generation antipsychotics use and reduced risk of pneumonia—Clinical implications in SARS-CoV2 treatment: A systematic review and meta-analysis of observational studies

Penfluridol Induced Extrapyramidal symptoms (EPS): A Case ReportSereen Rose Thomson, Balaji Ommurugan, Shalini Adiga, Navin Patil, Saurish Reddy

Timing methylprednisolone pulse therapy in COVID-19 infection-finding the sweet spot: a case series

Steroid therapy has been proven beneficial in the treatment of SARS-CoV2 in various trials all around the world. However, the dosing and timing of this therapy are crucial and still under debate. Studies exist regarding the use of Pulse IV therapy of steroids in this illness, but it has still not been widely used and accepted throughout the world. Here we describe four cases of SARS-CoV2 who presented to a tertiary care center in India within the first week of illness, with moderate to severe disease activity. These patients were treated with Pulse doses of intravenous MethylPrednisolone. All four patients showed positive outcomes in terms of oxygen requirement and early recovery.

Docking Studies on the Effects of Some Bioactive Compounds from Pistacia atlantica Desf. against Main Protease SARS-CoV2

Novel coronavirus which was named later as SARS-CoV2 appeared in Wuhan, China, in the end of December 2019. Actually, no precise drugs are existed and research concerning SARS-CoV2 treatment is deficient. SARS-CoV2 main protease (Mpro) was crystallized by Liu et al. (2020) and represented a crucial drug target. The present work aimed to evaluate some bioactive compounds from Pistacia atlantica as possible SARS-CoV2 Mpro inhibitors, based on molecular docking approach. Molecular docking was carried out using AutoDock Vina software. The results indicated that Beta-Eudesmol, Elemol, Verbenol, Pinocarvone, Myrtenal, Myrtenol and Trans-Carveol have a potential inhibitor activity of SARS-CoV2 Mpro. Nevertheless, further investigations are required to develop and optimize drug process to combat SARS-CoV2.

Treatment of COVID-19 patients with quercetin: a prospective, single center, randomized, controlled trial.

Scientific research continues on new preventive and therapeutic strategies against severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). So far, there is no proven curative treatment, and a valid alternative therapeutic approach needs to be developed. This study is designed to evaluate the effect of quercetin in COVID-19 treatment. This was a single-centre, prospective randomized controlled cohort study. Routine care versus QCB (quercetin, vitamin C, bromelain) supplementation was compared between 429 patients with at least one chronic disease and moderate-to-severe respiratory symptoms. Demographic features, signs, laboratory results and drug administration data of patients were recorded. The endpoint was that QCB supplementation was continued throughout the follow-up period from study baseline to discharge, intubation, or death. The most common complaints at the time of hospital admission were fatigue (62.4%), cough (61.1%), anorexia (57%), thirst (53.7%), respiratory distress (51%) and chills (48.3%). The decrease in CRP and ferritin levels was higher in the QCB group (all Ps were < 0.05). In the QCB group, the increase in platelet and lymphocyte counts was higher (all Ps were < 0.05). QCB did not reduce the risk of events during follow-up. Adjustments for statistically significant parameters, including the lung stage, use of favipiravir and presence of comorbidity did not change the results. While there was no difference between the groups in terms of event frequency, the QCB group had more advanced pulmonary findings. QCB supplement is shown to have a positive effect on laboratory recovery. While there was no difference between the groups in terms of event frequency, QCB supplement group had more advanced pulmonar findings, and QCB supplement is shown to have a positive effect on laboratory recovery/results. Therefore, we conclude that further studies involving different doses and plasma level measurements are required to reveal the dose/response relationship and bioavailability of QCB for a better understanding of the role of QCB in the treatment of SARS CoV-2.

Insuffisance rénale aiguë chez les patients COVID-19 en soins intensifs

L’insuffisance rénale aigue au cours de l’infection sévère par le SARS-CoV2 est fréquente, et est associée à une surmortalité. Elle est multifactorielle, associant des mécanismes non spécifiques (défaillance hémodynamique, PEP, iatrogénie) et des mécanismes plus spécifiques au COVID-19 (invasion virale, endothélite et thrombose, activation du système rénine angiotensine aldostérone, et élévation de cytokines pro-inflammatoires). Les troubles ioniques observés au cours de l’infection par la COVID-19 sont des marqueurs de gravité. La lésion histologique la plus fréquemment rencontrée est la nécrose tubulaire aiguë mais elle peut révéler des glomérulopathies. Il n’existe à ce jour aucun traitement spécifique de l’atteinte rénale du COVID-19.

Tongue ulcer in a patient with COVID-19: a case presentation

BackgroundThe emergence of COVID-19 has devastated many parts of the world. From asymptomatic to symptomatic, the virus causes a wide spectrum of presentations. COVID-19 patients may present with oral manifestations. In Afghanistan, where COVID-19 has severely strained the health care system, much of the population lacks proper oral hygiene. This makes the oral cavity a perfect site for SARS-CoV-2 to manifest clinical signs.Case presentationA 62-year-old male was evaluated in the Dentistry Teaching Clinic of Kabul University of Medical Sciences for a painful erosive lesion on dorsal surface of his tongue. He also complained of fever, cough, and taste alteration. He was referred to Afghan Japan Hospital for COVID-19 testing and tested positive. He was followed on for the treatment of SARS-CoV2. After 2 weeks, the patient tested negative and returned to the dentistry clinic for follow-up. Although there were no other signs of COVID-19, the painful erosive lesion on his tongue persisted. Oral evaluation were performed and the patient was advised to practice good hygiene. After 10 days, we observed an asymptomatic geographic tongue without fever and myalgias and the lesion of dorsal surface of tongue improved from severe condition to moderate.ConclusionIn conclusion, patients with suspected or confirmed SARS-CoV-2 should be screened for symptoms and physical findings in the oral mucosa To prevent such an outcome, awareness programs need to be implemented for the diagnosis and management of clinical symptoms among patients.

Interplay of Opposing Effects of the WNT/β-Catenin Pathway and PPARγ and Implications for SARS-CoV2 Treatment

The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has quickly reached pandemic proportions. Cytokine profiles observed in COVID-19 patients have revealed increased levels of IL-1β, IL-2, IL-6, and TNF-α and increased NF-κB pathway activity. Recent evidence has shown that the upregulation of the WNT/β-catenin pathway is associated with inflammation, resulting in a cytokine storm in ARDS (acute respire distress syndrome) and especially in COVID-19 patients. Several studies have shown that the WNT/β-catenin pathway interacts with PPARγ in an opposing interplay in numerous diseases. Furthermore, recent studies have highlighted the interesting role of PPARγ agonists as modulators of inflammatory and immunomodulatory drugs through the targeting of the cytokine storm in COVID-19 patients. SARS-CoV2 infection presents a decrease in the angiotensin-converting enzyme 2 (ACE2) associated with the upregulation of the WNT/β-catenin pathway. SARS-Cov2 may invade human organs besides the lungs through the expression of ACE2. Evidence has highlighted the fact that PPARγ agonists can increase ACE2 expression, suggesting a possible role for PPARγ agonists in the treatment of COVID-19. This review therefore focuses on the opposing interplay between the canonical WNT/β-catenin pathway and PPARγ in SARS-CoV2 infection and the potential beneficial role of PPARγ agonists in this context.

Mechanism and Pathways of Inhibitor Binding to the Human ACE2 Receptor for SARS-CoV1/2

Angiotensin converting enzyme 2 (ACE2) plays a key role in renin-angiotensin system regulation and amino acid homeostasis. Human ACE2 acts as the receptor for severe acute respiratory syndrome coronaviruses SARS-CoV and SARS-CoV2. ACE2 is widely expressed in epithelial cells of lungs, heart, kidney, and pancreas. It is an important drug target for treating pulmonary diseases, heart failure, hypertension, renal diseases and diabetes. It is also considered one of the primary targets for developing the treatment of SARS-CoV2.

559. Outcomes of Convalescent Plasma Transfusion for SARS-CoV2 Patients in the Intensive Care Unit

BackgroundSARS-CoV2 is a grave illness and few therapeutic agents have yielded benefit or reduced mortality. Administration of convalescent plasma (CP) in viral illnesses in the past, including SARS, before day 14, has been associated with a shorter hospital course. In the present study, we are interested in determining the benefit of administering CP to critically ill patients in the intensive care unit, and the impact on mortality and other clinical markers.Methods5 critically ill patients with confirmed SARS-CoV2 infection were observed in the uncontrolled case series study. Mechanically ventilated patients with severe ARDS (PaO2/FiO2 < 100) were eligible to receive CP transfusion. We reviewed daily vital signs, inflammatory markers, PaO2/FiO2 ratio and SOFA scores before and after CP transfusions. SARS-CoV2 PCR viral load testing was completed on day 0 of transfusion and repeated on day 3 and 6. Complications during the hospitalization and 30-day mortality were assessed.ResultsAll 5 patients were mechanically ventilated at the time of transfusion and between day 7 to 31 of their illness. Following plasma transfusion, body temperature and inflammatory markers remained elevated in four patients (figure 1). SOFA score and PaO2/FiO2 ratios continued to worsen in three and four patients respectively (figure 2). SARS-CoV2 PCR remained positive in 4 patients. 4 of the 5 patients had died at the end of the follow up period. One patient was successfully extubated on day 29 (table 1) and discharged after a long hospital course.Fever curve and trends of inflammatory markers Trends of SOFA socre and PaO2:FiO2 ratio Patient characteristics ConclusionIn our patient cohort, the administration of CP did not improve laboratory markers or clinical outcomes. Some notable limitations of this study are the small sample size, and that the patients received CP late in their disease course. Further investigation is necessary to draw definitive conclusions about the utility of CP in the treatment of SARS-CoV2.Disclosures All Authors: No reported disclosures

Potential drug interactions between hydroxychloroquine and anticholinesterase drugs

BackgroundOne of the main aggravating factors in the Covid‐19 pandemic is the lack of effective treatments capable of promoting a cure to date. Unfortunately, contrary to the recommendations of WHO and health authorities, in Brazil the use of Hydroxychloroquine in the treatment of SarsCov‐2 has been approved.MethodWe selected guidelines with recommendations for treatment of Covid 19, with an emphasis on the proposed treatments. Then we evaluate the main drug interactions and their potential risks.ResultThe risk of using Hydroxychloroquine in patients with Alzheimer's Disease is high, both due to the aspect of the disease itself, but also due to the drug interactions found.ConclusionHydroxychloroquine is not recommended for patients with Alzheimer's Disease.

Emetine Is Not Ipecac: Considerations for Its Use as Treatment for SARS-CoV2.

Emetine is a potent antiviral that acts on many viruses in the low-nM range, with several studies in animals and humans demonstrating antiviral activity. Historically, emetine was used to treat patients with Spanish influenza, in the last stages of the pandemic in the early 1900s. Some of these patients were “black” with cyanosis. Emetine rapidly reversed the cyanosis and other symptoms of this disease in 12–24 h. However, emetine also has been shown to have anti-inflammatory properties and it appears it is these anti-inflammatory properties that were responsible for the effects seen in patients with Spanish influenza. Emetine, in the past, has also been used in 10s to 100s of millions of people at a dose of ~60 mg daily to treat amoebiasis. Based on viral inhibition data we can calculate a likely SARS-CoV2 antiviral dose of ~1/10th the amoebiasis dose, which should dramatically reduce the risk of any side effects. While there are no anti-inflammatory dose response data available, based on the potential mode of action, the anti-inflammatory actions may also occur at low doses. This paper also examines the toxicity of emetine seen in clinical practice and that seen in the laboratory, and discusses the methods of administration aimed at reducing side effects if higher doses were found to be necessary. While emetine is a “pure drug” as it is extracted from ipecac, some of the differences between emetine and ipecac are also discussed.

The treatment of SARS-CoV2 with antivirals and mitigation of the cytokine storm syndrome: the role of gene expression.

In the absence of a vaccine, the treatment of SARS-CoV2 has focused on eliminating the virus with antivirals or mitigating the cytokine storm syndrome (CSS) that leads to the most common cause of death: respiratory failure. Herein we discuss the mechanisms of antiviral treatments for SARS-CoV2 and treatment strategies for the CSS. Antivirals that have shown invitro activity against SARS-CoV2, or the closely related SARS-CoV1 and MERS-CoV, are compared on the enzymatic level and by potency in cells. For treatment of the CSS, we discuss medications that reduce the effects or expression of cytokines involved in the CSS with an emphasis on those that reduce IL-6 because of its central role in the development of the CSS. We show that some of the medications covered influence the activity or expression of enzymes involved in epigenetic processes and specifically those that add or remove modifications to histones or DNA. Where available, the latest clinical data showing the efficacy of the medications is presented. With respect to their mechanisms, we explain why some medications are successful, why others have failed, and why some untested medications may yet prove useful.

In Search of Herbal Anti-SARS-Cov2 Compounds.

On March 11, 2020, the World Health Organization (WHO) announced that the spread of the new coronavirus had reached the stage of a pandemic. To date (23.10.2020), there are more than 40 million confirmed cases of the disease in the world, at the same time there is still no effective treatment for the disease. For management and treatment of SARS-Cov2, the development of an antiviral drug is needed. Since the representatives of all human cultures have used medicinal plants to treat viral diseases throughout their history, plants can be considered as sources of new antiviral drug compounds against emerging viruses. The huge metabolic potential of plants allows us to expect discovery of plant compounds for the prevention and treatment of coronavirus infection. This idea is supported by number of papers on the anti-SARS-Cov2 activity of plant extracts and specific compounds in the experiments in silico, in vitro, and in vivo. Here, we summarize information on methods and approaches aimed to search for anti-SARS-Cov2 compounds including cheminformatics, bioinformatics, genetic engineering of viral targets, interacting with drugs, biochemical approaches etc. Our mini-review may be useful for better planning future experiments (including rapid methods for screening compounds for antiviral activity, the initial assessment of the antiviral potential of various plant species in relation to certain pathogens, etc.) and giving a hand to those who are making first steps in this field.