Treatment Of COVID-19 Disease Research Articles

Medicinal Chemistry of Antisense Oligonucleotides for Therapeutic Use in SARS-CoV-2: Design Strategies and Challenges for Targeted Delivery

Background: The evolution of novel Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2) strains with greater degrees of infectivity, resistance to vaccine-induced acquired immunity, and more severe morbidity have contributed to the recent spread of COVID-19. In light of this, novel therapeutic alternatives with improved effectiveness and fewer side effects have become a necessity. Despite many new or repurposed antiviral agents recommended for Coronavirus disease (COVID-19) therapy, this objective remains unfulfilled. Under these circumstances, the scientific community holds the significant responsibility to develop classes of novel therapeutic modalities to combat SARS-CoV-2 with the least harmful side effects. Objective: Antisense Oligonucleotides (ASOs) are short single-stranded oligonucleotides that allow the specific targeting of RNA, leading to its degradation. They may also prevent cellular factors or machinery from binding to the target RNA. It is possible to improve the pharmacokinetics and pharmacodynamics of ASOs by chemical modification or bioconjugation, which may provide conditions for customization of a particular clinical target. This study aimed to outline the potential use of ASOs in the treatment of COVID-19 disease, along with the use of antisense stabilization and transfer methods, as well as future challenges and limitations. Methods: We have reviewed the structure and properties of ASOs containing nucleobase, sugar, or backbone modifications, and provided an overview of the therapeutic potential, delivery challenges, and strategies of ASOs in the treatment of COVID-19. Results: The first-line therapy for COVID-19-infected individuals, as well as the development of oligonucleotide-based drugs, warrants further investigation. Chemical changes in the oligonucleotide structure can affect the biological processes. These chemical alterations may lead to enhanced potency, while changing the pharmacokinetics and pharmacodynamics. Conclusion: ASOs can be designed to target both coding and non-coding regions of the viral genome to disrupt or completely degrade the genomic RNA and thereby eliminate SARS-CoV-2. They may be very effective in areas, where vaccine distribution is challenging, and they may be helpful for future coronavirus pandemics.

QSPR/QSAR study of antiviral drugs modeled as multigraphs by using TI’s and MLR method to treat COVID-19 disease

The ongoing COVID-19 pandemic continues to pose significant challenges worldwide, despite widespread vaccination. Researchers are actively exploring antiviral treatments to assess their efficacy against emerging virus variants. The aim of the study is to employ M-polynomial, neighborhood M-polynomial approach and QSPR/QSAR analysis to evaluate specific antiviral drugs including Lopinavir, Ritonavir, Arbidol, Thalidomide, Chloroquine, Hydroxychloroquine, Theaflavin and Remdesivir. Utilizing degree-based and neighborhood degree sum-based topological indices on molecular multigraphs reveals insights into the physicochemical properties of these drugs, such as polar surface area, polarizability, surface tension, boiling point, enthalpy of vaporization, flash point, molar refraction and molar volume are crucial in predicting their efficacy against viruses. These properties influence the solubility, permeability, and bio availability of the drugs, which in turn affect their ability to interact with viral targets and inhibit viral replication. In QSPR analysis, molecular multigraphs yield notable correlation coefficients exceeding those from simple graphs: molar refraction (MR) (0.9860), polarizability (P) (0.9861), surface tension (ST) (0.6086), molar volume (MV) (0.9353) using degree-based indices, and flash point (FP) (0.9781), surface tension (ST) (0.7841) using neighborhood degree sum-based indices. QSAR models, constructed through multiple linear regressions (MLR) with a backward elimination approach at a significance level of 0.05, exhibit promising predictive capabilities highlighting the significance of the biological activity IC50\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$IC_{50}$$\\end{document} (Half maximal inhibitory concentration). Notably, the alignment of predicted and observed values for Remdesivir’s with obs pIC50=6.01\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${pIC_{50} = 6.01}$$\\end{document},pred pIC50=6.01\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${pIC_{50} = 6.01}$$\\end{document} (pIC50\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$pIC_{50}$$\\end{document} represents the negative logarithm of IC50\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$IC_{50}$$\\end{document}) underscores the accuracy of multigraph-based QSAR analysis. The primary objective is to showcase the valuable contribution of multigraphs to QSPR and QSAR analyses, offering crucial insights into molecular structures and antiviral properties. The integration of physicochemical applications enhances our understanding of factors influencing antiviral drug efficacy, essential for combating emerging viral strains effectively.

Flavonoids derived from medicinal plants as a COVID-19 treatment.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 disease. Through its viral spike (S) protein, the virus enters and infects epithelial cells by utilizing angiotensin-converting enzyme 2 as a host cell's receptor protein. The COVID-19 pandemic had a profound impact on global public health and economies. Although various effective vaccinations and medications are now available to prevent and treat COVID-19, natural compounds derived from medicinal plants, particularly flavonoids, demonstrated therapeutic potential to treat COVID-19 disease. Flavonoids exhibit dual antiviral mechanisms: direct interference with viral invasion and inhibition of replication. Specifically, they target key viral molecules, particularly viral proteases, involved in infection. These compounds showcase significant immunomodulatory and anti-inflammatory properties, effectively inhibiting various inflammatory cytokines. Additionally, emerging evidence supports the potential of flavonoids to mitigate the progression of COVID-19 in individuals with obesity by positively influencing lipid metabolism. This review aims to elucidate the molecular structure of SARS-CoV-2 and the underlying mechanism of action of flavonoids on the virus. This study evaluates the potential anti-SARS-CoV-2 properties exhibited by flavonoid compounds, with a specific interest in their structure and mechanisms of action, as therapeutic applications for the prevention and treatment of COVID-19. Nevertheless, a significant portion of existing knowledge is based on theoretical frameworks and findings derived from in vitro investigations. Further research is required to better assess the effectiveness of flavonoids in combating SARS-CoV-2, with a particular emphasis on in vivo and clinical investigations.

Ultra-Low-Dose Computed Tomography Chest for Screening of COVID-19 Patients: Assessment of Radiation Dose Reduction

Abstract Introduction: Chest computed tomography (CT) scans have a significant role in the identification and treatment of COVID-19 disease. In earlier studies, the introduction of chest CT has been a highly sensitive method in testing COVID-19 pneumonia. With a radiation dose comparable to a chest X-ray, ultra-low-dose CT has been promised to be a successful method for lowering radiation dose and motion artifact. Materials and Methods: The research was carried out at a tertiary care facility’s radiology department between August 1 and August 31, 2020. A sum of 109 individuals aged over 18 years old and been called for a noncontrast CT scan chest and received were included. Results: The minimum age was 18 and the maximum was 87, where 14.67% of them are between 21 and 40 years, 40.37% of them are between 41 and 60 years and 44.96% of them are between 61 and 87 years. Male’s mean age is 55.89 years and female’s mean age is 60.14 years. The overall mean age is 57.02 years and standard deviation is 13.49 years. The average body mass index was 26.51 ± 3.5 kg/m2. In the standard dose and ultra-low-dose groups, the mean effective dose values were 6.70 ± 0.85 and 0.33 ± 0.09 mSv, respectively (P < 0.001). Conclusion: When identifying lung infiltrations among the patients admitted for elective or moderately urgent surgical or medical operations at the time of the COVID-19 pandemic, ultra-low-dose chest CT is an effective method that exposes patients to less radiation than standard dose CT.

The Therapeutic Monoclonal Antibody Bamlanivimab Does Not Enhance SARS-CoV-2 Infection by FcR-Mediated Mechanisms.

As part of the non-clinical safety package characterizing bamlanivimab (SARS-CoV-2 neutralizing monoclonal antibody), the risk profile for antibody-dependent enhancement of infection (ADE) was evaluated in vitro and in an African green monkey (AGM) model of COVID-19. In vitro ADE assays in primary human macrophage, Raji, or THP-1 cells were used to evaluate enhancement of viral infection. Bamlanivimab binding to C1q, FcR, and cell-based effector activity was also assessed. In AGMs, the impact of bamlanivimab pretreatment on viral loads and clinical and histological pathology was assessed to evaluate enhanced SARS-CoV-2 replication or pathology. Bamlanivimab did not increase viral replication in vitro, despite a demonstrated effector function. In vivo, no significant differences were found among the AGM groups for weight, temperature, or food intake. Treatment with bamlanivimab reduced viral loads in nasal and oral swabs and BAL fluid relative to control groups. Viral antigen was not detected in lung tissue from animals treated with the highest dose of bamlanivimab. Bamlanivimab did not induce ADE of SARS-CoV-2 infection in vitro or in an AGM model of infection at any dose evaluated. The findings suggest that high-affinity monoclonal antibodies pose a low risk of mediating ADE in patients and support their safety profile as a treatment of COVID-19 disease.

Prognostic significance of serum miR-18a-5p in severe COVID-19 Egyptian patients

BackgroundThe identification of miRNAs as well as characterization of miRNA-mRNA interactions in SARS-CoV-2 infection is important to understand their role in disease pathogenesis. Therefore the aim of the present study was to measure the expression levels of hsa-mir-18a-5p in the sera of severe COVID-19 Egyptian patients admitted to ICU to investigate its roles in the pathogenesis and severity of COVID-19 disease. MethodsA total of 180 unvaccinated severe COVID-19 patients were enrolled in our study. Besides the routine laboratory work, the expression level of hsa-mir-18a-5p was done using reverse transcription quantitative real-time PCR (RTqPCR) technique. Also, target genes of hsa-mir-18a-5p were explored by using online bioinformatics databases. ResultsThe expression level of hsa-mir-18a-5p decreased in nonsurvival severe COVID-19 patients (0.38 ± 0.26) when compared to the survival ones (0.84 ± 0.23). While as a prognostic tool for the prediction of bad prognosis and mortality among severe COVID-19 patients, our results showed that the serum hsa-mir-18a-5p expression level is a good sensitive and specific marker. By using bioinformatics tools, our results revealed that the decreased hsa-mir-18a-5p expression level may have a crucial role in COVID-19 pathogenesis and severity through decreased immunological responses (interpreted as lymphopenia) or increased inflammation (interpreted as increased serum levels of IL-6, CRP, LDH). ConclusionTaken together, the decreased expression level of hsa-mir-18a-5p could be a bad prognostic marker and therapeutic overexpression of hsa-mir-18a-5p could be a novel approach in the treatment of COVID-19 disease.

Native SEC and Reversed-Phase LC-MS Reveal Impact of Fab Glycosylation of Anti-SARS-COV-2 Antibodies on Binding to the Receptor Binding Domain.

The binding affinity of monoclonal antibodies (mAbs) for their intended therapeutic targets is often affected by chemical and post-translational modifications in the antigen binding (Fab) domains. A new two-dimensional analytical approach is described here utilizing native size exclusion chromatography (SEC) to separate populations of antibodies and bound antibody-antigen complexes for subsequent characterization of these modifications by reversed-phase (RP) liquid chromatography-mass spectrometry (LC-MS) at the intact antibody level. Previously, we utilized peptide mapping to measure modifications impacting binding. However, in this study, the large size of the modification (N-glycosylation) allowed assessing its impact from small amounts (∼20 ug) of intact antibody, without the need for peptide mapping. Here, we apply the native SEC-based competitive binding assay to quickly and qualitatively investigate the effects of Fab glycosylation of four antispike protein mAbs that were developed for use in the treatment of COVID-19 disease. Three of the mAbs were observed to have consensus N-glycosylation sites (N-X-T/S) in the Fab domains, a relatively rare occurrence in therapeutic mAbs. The goal of the study was to characterize the levels of Fab glycosylation present, as well as determine the impact of glycosylation on binding to the spike protein receptor binding domain (RBD) and the ability of the mAbs to inhibit RBD-ACE2 interaction at the intact antibody level, with minimal sample treatment and preparation. The three mAbs with Fab N-glycans were found to have glycosylation profiles ranging from full occupancy at each Fab (in one mAb) to partially glycosylated with mixed populations of two, one, or no glycan moieties. Competitive SEC analysis of mAb-RBD revealed that the glycosylated antibody populations outcompete their nonglycosylated counterparts for the available RBD molecules. This competitive SEC binding analysis was applied to investigate the three-body interaction of a glycosylated mAb blocking the interaction between endogenous binding partners RBD-ACE2, finding that both glycosylated and nonglycosylated mAb populations bound to RBD with high enough affinity to block RBD-ACE2 binding.

Quality of reporting of adverse events in clinical trials of covid-19 drugs: systematic review

ObjectiveTo assess the quality of reporting of adverse events in clinical trials of covid-19 drugs based on the CONSORT (Consolidated Standards of Reporting Trials) harms extension and according to clinical...

The Importance of Antioxidant/Anti-inflammatory Vitamins during the SARS-CoV-2 Infection

Coronavirus 2019 (COVID-19), an epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), has spread worldwide since it was first identified in Wuhan, China, in December 2019, leading to outbreaks of epidemics. Due to the increasing spread of this disease, definitive treatment and approved vaccines have not been found for it. In this study, we reviewed recent articles on the effect of vitamins (including vitamins A, B, and E) for treating coronavirus. This result suggests that some dietary supplements such as vitamins (A, B, C, D, E, etc.) have antiviral, antioxidant, and anti-inflammatory effects. Dietary supplements consisting of vitamins and individual dietary habits can therefore be used as adjunctive therapy along with antiviral drugs in the treatment of COVID-19 disease.

QSPR Study and Distance-Based New Topological Descriptors of Some Drugs Used in the COVID-19 Treatment

In chemistry and medical sciences, it is essential to study the chemical, biological, clinical, and therapeutic aspects of pharmaceuticals. To save time and money, mathematical chemistry focuses on topological indices used in quantitative structure-property relationship (QSPR) models to predict the properties of chemical structures. The COVID-19 pandemic is widely recognized as the greatest life-threatening crisis facing modern medicine. Scientists have tested various antiviral drugs available to treat COVID-19 disease, and some have found that they help get rid of this viral infection. Antiviral drugs such as Arbidol, chloroquine, hydroxychloroquine, lopinavir, remdesivir, ritonavir, thalidomide, and theaflavin are used to treat COVID-19. In this paper, reformulated leap Zagreb indices are introduced. Then, the reformulated leap Zagreb indices, leap eccentric connectivity indices, and reformulated Zagreb connectivity indices of these antiviral drugs are calculated. Curvilinear and multilinear regression models predicting the physicochemical properties of these antiviral drugs in terms of proposed indices are obtained and analyzed. The findings and models of this study will shed light on new drug discoveries for the treatment of COVID-19.

Tucaresol: A Unique Oral Candidate Drug Ideally Accessible For Treatment Of Covid-19 Disease

The SARS-CoV-2 pandemic has significantly impacted world health and economic status. In response, much work has been undertaken to provide effective, safe vaccines, antibodies and antiviral drugs with which to address this pandemic. Treatment of a pandemic population presents multiple challenges in addition to the primary issue of drug efficacy and safety, such as large scale drug manufacture and distribution, drug stability, oral dosing and pharmacoeconomic considerations. Ideally, these factors must be addressed if new candidate drugs are to be advanced for treatment of large (pandemic) populations. Subsequently, new antivirals have reached the market but choices are few. According to the NIH Covid Treatment Guidelines, only three small molecule antiviral drugs are available to treat COVID-19 disease. As such, a significant part of the research towards discovery of new antiviral drugs has focused on screening and evaluation of ‘repurposed drugs’ or previously approved or clinical stage drugs. Yet, in spite of this increased research activity, one promising clinical stage candidate drug has received little attention regarding its potential as a monotherapy or component of combination therapy for treatment of COVID-19 disease. Tucaresol, with documented human safety and pharmacokinetic data, is an orally active, stable, small molecule amenable to large scale manufacture by a proprietary two-step synthesis developed by us. Tucaresol functions as a host-targeted antiviral by selective protection/reconstitution of CD4+ T helper cells as demonstrated in HIV patients and SIV macaques. In view of similarities between HIV and SARS-CoV-2, especially with respect to host CD4+ T helper cells, and the suitability of Tucaresol for facile treatment of pandemic populations, Tucaresol is presented herein for treatment of mild-to-moderate COVID-19 patients but may also be useful for treatment of advanced disease accompanied by lymphopenia.

Coating of favipiravir (FVP) on silver nanoparticles: First principle study

Silver nanoparticles, thanks to their antiviral and antibacterial properties, have great potential in a variety of applications, such as drug-delivery carriers. The coating properties of silver nanoparticles (size range of 1.6 nm) with a well-known drug, Favipirair, were investigated in this study using quantum mechanical and classical atomistic molecular dynamics simulation in order to use as the drug delivery to treat COVID-19 disease. The drug molecule's optimized structure, frequencies, charge distribution, and electrostatic potential maps were simulated using density functional theory (DFT) at the B3LYP/6–311++g(d,p) level of theory. The coating of AgNP with each of these drugs was then studied using molecular dynamics simulation. The interaction affinity obtained from MD results agrees with the DFT results on drug adsorption on the Ag(111) slab.

Evaluation of post-vaccination antibody response of biochemical analysis in SARS-CoV-2 inactivated vaccine strategy

<b>Introduction:</b> The importance of academic equipment in biochemical and microbiological evaluations of SARS-CoV-2 is increased. In this context, different techniques have been developed in the diagnosis and treatment of COVID-19 disease as qRT-PCR, rapid antigen tests and vaccine technology. The first known example of vaccine technology is the CoronaVac (Sinovac, China) inactivated vaccine throughout pandemic. In the presented study, the sensitivity of CoronaVac in the community would be positively increased and this data would be strengthened. In addition, antibody sensitivity of the CoronaVac between two doses, as well as the hemogram and biochemical analyzes were evaluated. The focus will be on increasing the sensitivity of the society to the vaccine.<br /> <b>Materials and methods:</b> The immunoglobulin, biochemical analyzes, hemogram, and iron-iron binding capacities were evaluated after vaccinated person in a vaccine administration center in Istanbul, Türkiye.<br /> <b>Results:</b> RBDIgG level was significantly higher after second dose (p<0.05). Mon#, Bas#, IMG#, Mon, Hgb, MCH, MCHC, RDWCV, RDWSD, and PDW levels were higher at 28<sup>th</sup> day. RBDIgG, Fe, WBC, Neu#, Lym#, Eos#, and PLT levels were higher at 42<sup>nd</sup> day. All other parameter means were higher at 56<sup>th</sup> day. RBDIgG, Fe, WBC, RDWCV, RDWSD and PDW differences between 28<sup>th</sup> and 42<sup>nd</sup> days were significant (p<0.05). RBDIgG, HCT, MCV, MCH, MCHC, and RDWCV differences between 28<sup>th</sup> and 56<sup>th</sup> days were statistically significant (p<0.05). RBDIgG, MCV and MCH differences between 42<sup>nd</sup> and 56<sup>th</sup> days were statistically significant (p<0.05).<br /> <b>Discussion and conclusion: </b>The 60 volunteers in our study were laboratory, emergency service staffes and hospital personnel working at high risk of COVID-19. There was no differentiation in blood values related to the vaccine. It has been shown as an example of the phase-1 and the side effects of the CoronaVac, were also evaluated, and all our volunteers were followed for 60 days, and no possible serious side effects were observed. In groups with statistical significance in blood results, a vaccine related observation is not clearly revealed. We see that CoronaVac vaccine offers a positive confidence interval in antibody responses after the 2<sup>nd</sup> dose. These data are great importance in terms of better monitoring of the data by the anti-vaccine groups in Türkiye. It is beneficial to remove the vaccine mistrust against the anti-vaccination and pave the way for social immunization. This study contributes to the accuracy of the ministry and the vaccination strategy implemented in Türkiye. The result of this study provides preliminary information for the studies that will result from the application of the 3<sup>rd</sup> and 4<sup>th</sup> dose of vaccines.

Tucaresol: A Unique Oral Candidate Drug Ideally Accessible for Treatment Of COVID-19 Disease

The SARS-CoV-2 pandemic has significantly impacted world health and economic status. In response, much work has been undertaken to provide effective, safe vaccines, antibodies and antiviral drugs with which to address this pandemic. Treatment of a pandemic population presents multiple challenges in addition to the primary issue of drug efficacy and safety, such as large-scale drug manufacture and distribution, drug stability, oral dosing and pharmacoeconomic considerations. Ideally, these factors must be addressed if new candidate drugs are to be advanced for treatment of large (pandemic) populations. Subsequently, new antivirals have reached the market but choices are few. According to the NIH Covid Treatment Guidelines, only three small molecule antiviral drugs are available to treat COVID-19 disease. As such, a significant part of the research towards discovery of new antiviral drugs has focused on screening and evaluation of ‘repurposed drugs’ or previously approved or clinical stage drugs. Yet, in spite of this increased research activity, one promising clinical stage candidate drug has received little attention regarding its potential as a monotherapy or component of combination therapy for treatment of COVID-19 disease. Tucaresol, with documented human safety and pharmacokinetic data, is an orally active, stable, small molecule amenable to large scale manufacture by a proprietary two-step synthesis developed by us. Tucaresol functions as a host- targeted antiviral by selective protection/reconstitution of CD4+ T helper cells as demonstrated in HIV patients and SIV macaques. In view of similarities between HIV and SARSCoV-2, especially with respect to host CD4+ T helper cells, and the suitability of Tucaresol for facile treatment of pandemic populations, Tucaresol is presented herein for treatment of mild-to- moderate COVID-19 patients but may also be useful for treatment of advanced disease accompanied by lymphopenia.

Components of Good Governance in the Corona Era by Looking at the Approvals of the National Anti-Corona Headquarters (with Emphasis on the Legal and Managerial Dimension)

Corona is a global crisis that has affected government systems. The transition from crisis to crisis requires prudent measures. Governance is a continuous process through which conflicting interests are harmonized and cooperative actions are taken. The latest theory in this concept is good governance, which is doubly important in times of crisis. Good governance is the product of the favorable participation of the three institutions of government, civil society and the private sector. The components of good governance are numerous from the perspective of the World Bank, the United Nations, and thinkers in this field. The National Anti-Corona Headquarters was established by the order of the Supreme Leader and based on the approval of the Supreme National Security Council in March 2020 to take appropriate decisions regarding the treatment of Covid-19 disease, including announcing closures and other restrictive measures in case of violation of health instructions. In this research, with a descriptive-analytical method, an attempt has been made to explain the components of good governance in this period according to the unique legislative approvals in this field, while determining the competence of the mentioned headquarters in regulating. From the authors' point of view, the approvals of the Corona National Headquarters as one of the sub-councils of the Supreme National Security Council are beyond the ordinary law and among the existing components; Efficiency and effectiveness, transparency and accountability and pivotal consensus were recognized.

COVID-19 (SARS-COV-2) structural features, pathophysiology and current drug therapy

The 2019 coronavirus pandemic disease has spread globally. SARS-CoV-2 species in the first and second time waves and new species of Omicron show symptoms in the third wave of COVID-19 worldwide. The first patients were found in Wuhan, China. Due to COVID-19, the main highly infected countries are the U.S. China, European countries, and also India. The SARS-CoV-2 species are betacoronavirus infections that spread from person to person and another object. The COVID-19 SARS species (RNA virus) is majorly infected in the lungs. Some vaccines and some drugs are provided worldwide, but these vaccines are not proper treatment for COVID-19. These vaccines boost immunity and provide relief from the symptoms of COVID-19, but they are not a proper treatment. Antimalarial drugs, antiviral drugs, monoclonal antibodies, and antibiotics are used in the current treatment to stop mechanisms like fusion entry and replication. Identification of COVID-19 through symptoms and properly identified by RT-PCR Prevention and treatment of COVID-19 disease is a promising new research area for pharma companies to develop novel therapeutic agents' inhibition for COVID-19 pathological targets.

Pain in COVID-19: Quis est culpa?

<b>Background</b>: At present, during the coronavirus disease (COVID-19) pandemic, chronic pain is becoming more prominent, and it is also associated with the post-COVID-19 syndrome. Thanks to quick decisions on the therapy and as part of COVID-19 prevention, we have succeeded in stabilising the situation all over the world. On the other hand, ‘quick decisions’ have contributed to other significant issues which we are beginning to deal with now: in the effort to defeat the virus, many experts regarded the adverse effects of the medications used to be of secondary importance.<br /> <b>Purpose:</b> The article aims to demonstrate the side effects of treatment with various drugs (and their combinations) that are used to treat COVID-19 disease.<br /> <b>Method: </b>From the beginning of January until mid-May, the COVID-19 department of the 2nd Surgical Clinic of the Faculty of Medicine of the Comenius University in Bratislava (University Hospital Bratislava, Hospital of Saints Cyril and Methodius) treated 221 patients with moderate and severe course of COVID-19 (2nd wave of the pandemic). We saw some adverse effects and lack of effect of certain drugs for COVID-19.<br /> <b>Results: </b>The benefits of preventive measures compared to treatment are enormous. For example, corticoids can impair metabolism, cause diabetes, or suppress immunity. Antibiotics may cause colitis and blood pressure medications may negatively impact blood circulation.<br /> <b>Conclusion: </b>Preventive measures such as vaccination and activation of intrinsic antiviral immune systems are based on an incomparable benefit. Important in the process of the activation of antiviral immunity (linked to interferon synthesis) in the prevention of COVID-19 is the improvement of vitamin D deficit and the use of other micronutrients.<br /> <b>Practical value:</b> The results of the study will be valuable in the field of medicine, for virologists, pharmacologists, pharmacists, and medical professionals.

In Silico Screening of Some Anti-Cancer Drugs Against the Main Protease of COVID-19 Using Molecular Docking

Abstract:The SARS-CoV-2 pandemic has led to major worldwide health concerns. Design and detection of effective drugs and adjuvant therapies to treat COVID-19 disease in the shortest possible time have become one of the most critical global challenges. In this study, we investigated the effect of some anticancer drugs against the COVID-19 main protease (Mpro/3CLpro) to detect an effective treatment, using a molecular docking approach as a fast and cost-effective method. Accordingly, 44 anticancer drugs were selected as a target for the virtual screening. The molecular docking study was carried out using AutoDock Tools (ADT), AutoDock Vina, Discovery Studio, and Open Babel software. Tucatinib, selinexor, irinotecan, olaparib, dacomitinib, lapatinib, ibrutinib, and pazopanib were ranked top as COVID-19 inhibitors with the respective binding energy of -10.1, -9.4, -9.2, -8.9, -8.7, -8.7, -8.6, and -8.5 kcal/mol. Among the drugs tested, tucatinib displayed the highest binding affinity and strong interactions with the active site of COVID-19 3CLpro (-10.1 kcal/mol). Pharmacokinetics properties and drug-likeness of the top 8 selected anticancer drugs were evaluated. The results showed that these drugs could be utilized as potential inhibitors against the main protease of COVID-19, which can help control the spread of this disease. However, in vitro, in vivo studies, and clinical trials will help evaluate the efficacy of these drugs against COVID-19.

1131. Evaluation of drug-drug interaction potential of ensitrelvir for CYP3A by clinical studies and physiologically-based pharmacokinetic model

Abstract Background Ensitrelvir is a new drug candidate to treat COVID-19 disease. According to the in vitro drug-drug interaction (DDI) study, time-dependent inhibition by ensitrelvir was observed on cytochrome P450 3A (CYP3A). The purpose of this study was to evaluate the effect of ensitrelvir on the pharmacokinetics (PK) of CYP3A substrates by clinial DDI studies and physiologically-based pharmacokinetic (PBPK) analyses. Methods Clinical studies: The effect of once daily multiple-doses of ensitrelvir with the loading dose on Day 1/ maintenance dose (750/250 mg) for 6 days on the PK of midazolam (MDZ) was assessed. MDZ was administered on Days -2 and 6. The effects of once daily multiple-doses of ensitrelvir with 750/250 mg for 5 days on the PK of dexamethasone (DXS) and prednisolone (PLS) were also assessed because these corticosteroids were also CYP3A substrates. DXS and PLS were administered on Days -2, 5 (co-administration with ensitrelvir), 9 and 14 to evaluate the effects after the last dose of ensitrelvir. PBPK analyses: The effects of once daily multiple-doses of ensitrelvir with another dose regimen (the loading dose/mentenance dose [375/125 mg] for 5 days) on the PK of CYP3A substrates were predicted using Simcyp PBPK Simulator (Version 20, Certara UK Limited, UK). Results The AUC0-inf of MDZ co-administered with ensitrelvir was increased by 8.80-fold compared to those of MDZ alone, indicating that ensitrelvir is a strong CYP3A inhibitor with 750/250 mg for 6 days. The AUC0-inf of DXS on Day 5 was increased 3.47-fold and the effect of ensitrelvir on the PK of DXS was diminished over time after the last dose of ensitrelvir. The AUC0-inf of PLS on Day 5 was increased 1.25-fold and no clinically meaningful effect of ensitrelvir on the PK of PLS was observed. The PBPK analyses predicted that the co-administration of ensitrelvir increased the AUC of MDZ by 3.83-fold and the AUC of DXS by 2.49-fold following ensitrelvir at 375/125 mg for 5 days. A clinical study with MDZ under the analyses conditions is underway to confirm the PBPK results. Conclusion The clinical study revealed that ensitrelvir affects the PK of CYP3A substrates with 750/250 mg for 5 or 6 days. The PBPK analyses suggests that ensitrelvir is expected to a moderate inhibitor of CYP3A with 375/125 mg for 5 days. Disclosures Ryosuke Shimizu, Shionogi & Co., Ltd.: employee Kana Horiuchi, Shionogi & Co., Ltd.: employee Hiroki Koshimichi, n/a, Shionogi & Co., Ltd.: employee Takanobu Matsuzaki, Ph.D., Shionogi & Co., Ltd.: Employee Shinpei Yoshida, Ph.D., Shionogi & Co., Ltd.: employee Shingo Sakamoto, n/a, Shionogi & Co., Ltd.: employee Ryuji Kubota, Ph.D., Shionogi & Co., Ltd.: employee|Shionogi & Co., Ltd.: employee.

The role of gum Arabic as an anti-inflammatory, antioxidant, and immune modulator in the development of COVID-19: A review

Background: Down-regulation of the lung inflammatory response seems to preserve pulmonary functions and improve survival in COVID-19. The key factor in overcoming the cytokine storm caused by COVID-19 by immunomodulation, rather than immunosuppression. Identifying the right mechanism to manipulate the immune regulatory networks in the lung—with minimal side effects—represents one of the many challenges in the treatment of COVID-19 disease. Immunomodulatory, anti-inflammatory, antioxidant, and gut-regulatory activities are the most significant properties of prebiotics. Therefore, it could be beneficial to consider them as an adjuvant dietary intervention among COVID-19 patients. Understanding the exact mechanism of prebiotic defense against infection and regulation of immune processes involved in COVID-19 are crucial for the development of novel therapeutic agents. Several studies considered Gum Arabic (GA) as a potent prebiotic with cytoprotective properties. This review aims to discuss and display the possibility of utilizing the beneficial effects of GA to modulate COVID-19 pathogenesis.Keywords: COVID-19, Gum Arabic, Immunomodulation, dietary intervention, Gut microbiota, Anti-inflammatory, Antioxidant