COVID-19: An Update on the Latest Therapeutic Agents

The COVID-19 pandemic has plagued the world for over three years since discovering the causative virus, SARS-CoV-2, in China. The rampant spread of the virus led to the loss of livelihoods of millions across the globe. This public health emergency prompted the rapid development of vaccines and treatments to fight against viral infection. Vaccines against the viral infection started rolling out in late 2020, and the distribution of the vaccines worldwide managed to reduce the symptoms of COVID-19 and prevent outbreaks in local communities. However, COVID-19 infections are still prevalent, with patients suffering from severe symptoms which require oxygen support or mechanical ventilation. Thus, therapeutic agents for COVID-19 play a significant role in reducing the risk of disease progression into severe disease and improving hospitalized patients' clinical outcomes. Existing drugs such as remdesivir, molnupiravir, baricitinib, anakinra, and tocilizumab have been repurposed to treat COVID-19 earlier during the pandemic to meet the urgent demand for treatment. There are also novel antiviral and immunomodulating treatments (nirmatrelvir plus ritonavir, ensitrelvir, regdanvimab, sotrovimab, and vilobelimab) that were developed during the pandemic to fight against COVID-19 infections. These therapeutic agents have been reported to be effective and safe for use to treat COVID-19 infections of different severity. Nevertheless, continuous surveillance is imperative in ensuring that these treatment methods maintain efficacy and safety profiles in treating COVID-19 caused by different variants of the virus. © 2023, HH Publisher. All rights reserved.

Epilepsy in Dravet Syndrome-Current and Future Therapeutic Opportunities.

Dravet Syndrome (DS) is a developmental epileptic encephalopathy characterized by drug-resistant seizures and other clinical features, including intellectual disability and behavioral, sleep, and gait problems. The pathogenesis is strongly connected to voltage-gated sodium channel dysfunction. The current consensus of seizure management in DS consists of a combination of conventional and recently approved drugs such as stiripentol, cannabidiol, and fenfluramine. Despite promising results in randomized clinical trials and extension studies, the prognosis of the developmental outcomes of patients with DS remains unfavorable. The article summarizes recent changes in the therapeutic approach to DS and discusses ongoing clinical research directions. Serotonergic agents under investigation show promising results and may replace less DS-specific medicines. The use of antisense nucleotides and gene therapy is focused not only on symptom relief but primarily addresses the underlying cause of the syndrome. Novel compounds, after expected safe and successful implementation in clinical practice, will open a new era for patients with DS. The main goal of causative treatment is to modify the natural course of the disease and provide the best neurodevelopmental outcome with minimum neurological deficit.

SARS‑CoV‑2 infection and children: Insights from the 6th Workshop on Paediatric Virology (Review)

The present article provides an overview of the key messages of the plenary lectures on severe acute respira‑ tory syndrome coronavirus type 2 (SARS‑CoV‑2) infection in children, which were presented at the ‘6th Workshop on Paediatric Virology' organised by the Institute of Paediatric Virology on October 24, 2020. SARS‑CoV‑2 is a novel © 2021 Polish Otolaryngology Society. All rights reserved.

Plant-derived nanovesicles: further exploration of biomedical function and application potential

Extracellular vesicles (EVs) are phospholipid bilayer vesicles actively secreted by cells, that contain a variety of functional nucleic acids, proteins, and lipids, and are important mediums of intercellular communication. Based on their natural properties, EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers. Among them, plant-derived nanovesicles (PNVs) are characterized as natural disease therapeutics with many advantages such as simplicity, safety, eco-friendliness, low cost, and low toxicity due to their abundant resources, large yield, and low risk of immunogenicity in vivo. This review systematically introduces the biogenesis, isolation methods, physical characterization, and components of PNVs, and describes their administration and cellular uptake as therapeutic agents. We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers, including anti-inflammatory, anticancer, wound healing, regeneration, and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19. Finally, the toxicity and immunogenicity, the current clinical application, and the possible challenges in the future development of PNVs were analyzed. We expect the functions of PNVs to be further explored to promote clinical translation, thereby facilitating the development of a new framework for the treatment of human diseases.Copyright © 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences

Enveloped Viruses: Pathogenetic Targets for Cyanobacterial Lectins.

Lectins are a group of highly specific carbohydrate-binding proteins with a wide spectrum of action, involved in the so-called <<first line>> of body defense. These unique biomolecules show high specificity for various mono- and oligosaccharides, primarily for viral and bacterial glycoconjugates. Cyanobacteria lectins are effective against enveloped viruses and are an appealing alternative to existing synthetic drugs. Virtually complete absence of resistance formation in viruses to these compounds is known. The purpose of this review is to analyze, summarize, and discuss the results of experimental studies in vivo and in vitro, illustrating the mechanisms of action and antiviral effects of lectins obtained from cyanobacteria in relation to the most dangerous and socially significant viruses: SARS-Cov-2, HIV, Ebola viruses, influenza, and hepatitis C. In addition, the article outlines some of the challenges that must be overcome in order to obtain effective antiviral drugs in the future.Copyright © Team of Authors, 2022.

Enveloped Viruses: Pathogenetic Targets for Cyanobacterial Lectins.

Lectins are a group of highly specific carbohydrate-binding proteins with a wide spectrum of action, involved in the so-called <<first line>> of body defense. These unique biomolecules show high specificity for various mono- and oligosaccharides, primarily for viral and bacterial glycoconjugates. Cyanobacteria lectins are effective against enveloped viruses and are an appealing alternative to existing synthetic drugs. Virtually complete absence of resistance formation in viruses to these compounds is known. The purpose of this review is to analyze, summarize, and discuss the results of experimental studies in vivo and in vitro, illustrating the mechanisms of action and antiviral effects of lectins obtained from cyanobacteria in relation to the most dangerous and socially significant viruses: SARS-Cov-2, HIV, Ebola viruses, influenza, and hepatitis C. In addition, the article outlines some of the challenges that must be overcome in order to obtain effective antiviral drugs in the future.Copyright © Team of Authors, 2022.

Lactoferrin as a Possible Preventive and Therapeutic Agent Against SARS-CoV-2 Infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of novel coro-navirus disease 2019 (COVID-19), a major cause of atypical pneumonia worldwide. Elderly individuals and those with underlying illnesses, such as cardio-vascular and pulmonary diseases, are at a high risk of experiencing severe symptoms and have high mortality rates. There is therefore a major need to develop additional vaccines, effective treatments, and complementary drugs to control this infection. Lactoferrin (LF), a naturally-occurring glycoprotein, is bioactive against viruses and other pathogens. LF has a unique immunomodulatory function and is indispensable for immunity in infants. It is thought to contribute to biological defense in individuals across all generations, not only infants. LF inhibits viral adhesion to host cell surfaces through ionic binding to glycosaminoglycans and/or specific binding to viral structures. Purified LF is cost-effective and orally available as a dietary sup-plement. Here, we review studies on the protective role of LF against common viral infections. Based on this review, we propose that LF can be a possible prophy-lactic or therapeutic agent for COVID-19 disease. © Fuji Technology Press Ltd.

Supplement of iron abrogates SARS-CoV-2 pseudovirus infection in a 3D model of vascularized organoids

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause severe outbreak of coronavirus disease 2019 (COVID-19). Even though vaccination, the spread of SARS-CoV-2 is still continue. It is urgent to have a model that can efficiently evaluate potential therapeutic agents to counteract SARS-CoV-2 infection. Iron is an essential molecule for maintaining homeostasis. Supplement of iron significantly to affect virus infection. But the detailed mechanisms of iron on regulating SARS-CoV-2 infection are still unveiled. The three-dimensional (3D) model is a promising system for drug screening and disease progression analysis. Organoid is a typical 3D culture system that recapitulates genetic characteristics and phenotypic features of organs within body. Vasculature is prevalent for all various organs or tumors in the body which transport nutrients, oxygen and metabolites to maintain cellular homeostasis. Thus, we have established a 3D model of vascularized organoid to evaluate the effects of iron on infectivity of SARS-CoV-2 pseudovirus to provide the novel therapeutic strategy in coping SARS-CoV-2 infection. © 2022 IEEE.

Pharmaceutical, biological agents, and vaccines under clinical trials for COVID-19 and roles of pharmacists to combat COVID-19, an update

Due to the high mortality rate and rapid spread in the early phase of the COVID-19 pandemic, the healthcare system used various treatment options. The pathology associated with COVID-19 includes inflammatory responses which ultimately lead to multi-system organ failure or "cytokines storm". Treating COVID-19 at the initial stage of pandemic has become a challenge as there are no medications that have yet been approved by the FDA or other regulatory agencies. There are many medications have been used by the practitioners to combat the severity of the inflammatory responses. This article summarized the repurposed medications that have received attention during the COVID-19 pandemic and provided an outline of the therapeutic agents, which are under clinical trial that may be helpful to treat COVID-19. This article also emphasizes on pharmacist roles and responsibilities during disasters and pandemics and discussed various vaccines undergoing clinical trials currently. Copyright © 2022 Marmara University Press.

Analysis and identification of potential type II helper T cell (Th2)-Related key genes and therapeutic agents for COVID-19.

COVID-19 pandemic poses a severe threat to public health. However, so far, there are no effective drugs for COVID-19. Transcriptomic changes and key genes related to Th2 cells in COVID-19 have not been reported. These genes play an important role in host interactions with SARS-COV-2 and may be used as promising target. We analyzed five COVID-19-associated GEO datasets (GSE157103, GSE152641, GSE171110, GSE152418, and GSE179627) using the xCell algorithm and weighted gene co-expression network analysis (WGCNA). Results showed that 5 closely correlated modular genes to COVID-19 and Th2 cell enrichment levels, including purple, blue, pink, tan and turquoise, were intersected with differentially expressed genes (DEGs) and 648 shared genes were obtained. GO and KEGG pathway enrichment analyses revealed that they were enriched in cell proliferation, differentiation, and immune responses after virus infection. The most significantly enriched pathway involved the regulation of viral life cycle. Three key genes, namely CCNB1, BUB1, and UBE2C, may clarify the pathogenesis of COVID-19 associated with Th2 cells. 11 drug candidates were identified that could down-regulate three key genes using the cMAP database and demonstrated strong drugs binding energies aganist the three keygenes using molecular docking methods. BUB1, CCNB1 and UBE2C were identified key genes for COVID-19 and could be promising therapeutic targets.

Antimicrobial peptides: features, applications and the potential use against covid-19.

BACKGROUND: Antimicrobial peptides (AMPs) are a diverse class of molecules that represent a vital part of innate immunity. AMPs are evolutionarily conserved molecules that exhibit structural and functional diversity. They provide a possible solution to the antibiotic-resistance crisis. MAIN TEXT: These small cationic peptides can target bacteria, fungi, and viruses, as well as cancer cells. Their unique action mechanisms, rare antibiotic-resistant variants, broad-spectrum activity, low toxicity, and high specificity encourage pharmaceutical industries to conduct clinical trials to develop them as therapeutic drugs. The rapid development of computer-assisted strategies accelerated the identification of AMPs. The Antimicrobial Peptide Database (APD) so far contains 3324 AMPs from different sources. In addition to their applications in different fields, some AMPs demonstrated the potential to combat COVID-19, and hinder viral infectivity in diverse ways. CONCLUSIONS: This review provides a brief history of AMPs and their features, including classification, evolution, sources and mechanisms of action, biosynthesis pathway, and identification techniques. Furthermore, their different applications, challenges to clinical applications, and their potential use against COVID-19 are presented.

Extracellular Vesicles and Acute Kidney Injury: Potential Therapeutic Avenue for Renal Repair and Regeneration.

Acute kidney injury (AKI) is a sudden decline of renal function and represents a global clinical problem due to an elevated morbidity and mortality. Despite many efforts, currently there are no treatments to halt this devastating condition. Extracellular vesicles (EVs) are nanoparticles secreted by various cell types in both physiological and pathological conditions. EVs can arise from distinct parts of the kidney and can mediate intercellular communication between various cell types along the nephron. Besides their potential as diagnostic tools, EVs have been proposed as powerful new tools for regenerative medicine and have been broadly studied as therapeutic mediators in different models of experimental AKI. In this review, we present an overview of the basic features and biological relevance of EVs, with an emphasis on their functional role in cell-to-cell communication in the kidney. We explore versatile roles of EVs in crucial pathophysiological mechanisms contributing to AKI and give a detailed description of the renoprotective effects of EVs from different origins in AKI. Finally, we explain known mechanisms of action of EVs in AKI and provide an outlook on the potential clinical translation of EVs in the setting of AKI.

Analysis of COVID-19 prevention and treatment in Taiwan.

Coronavirus disease 2019 (COVID-19) has been spreading worldwide with a mind-boggling speed. According to a statement from World Health Organization (WHO), COVID-19 has infected more than six billions people and caused more than one and half million passing in the world. Based on previous experience with SARS, the Taiwanese government had decided to block viral transmission during its early stages. This review sums up the clinical characteristics, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) viral infection process, diagnostic methods, preventive strategy, and the executive proportions of COVID-19, as well as the name-based mask distribution system (NBMDS) in Taiwan. We also give a review of the conceivable sub-atomic pharmacologic systems against SARS-CoV-2 specialists and the blend of remdesivir (GS-5734), chloroquine (CQ), and hydroxychloroquine (HCQ). Lastly, we summarized the therapeutic agents against COVID-19 as mentioned by COVID-19 treatment guidelines. In this review, development of novel anti-SARS-CoV-2 viral agents, vaccines for COVID-19 therapy or an effective combination therapy can be expected based on all the information accumulated. Last but not least, we might want to stretch out our best respects to all medical providers in their worldwide battle against COVID-19.

Effect of pharmacological interventions on lipid profiles and C-reactive protein in polycystic ovary syndrome: A systematic review and meta-analysis.

CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive protein (CRP), which increase the risks of cardiovascular disease (CVD). OBJECTIVE: To review the existing evidence on the effects of different pharmacological interventions on lipid profiles and CRP of women with PCOS. DATA SOURCES: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library, and Web of Science in April 2020 and updated the results in March 2021. STUDY SELECTION: The study included randomized controlled trials (RCTs) and follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). DATA EXTRACTION: Two independent researchers extracted data and assessed for risk of bias using the Cochrane risk of bias tool. Covidence systematic review software were used for blinded screening and study selection. DATA SYNTHESIS: In 29 RCTs, there were significant reductions in triglycerides with atorvastatin versus placebo [mean difference (MD): -0.21 mmol/L; 95% confidence interval (CI): -0.39, -0.03, I2 = 0%, moderate grade evidence]. Significant reductions were seen for low-density lipoprotein cholesterol (LDL-C) with metformin versus placebo [standardized mean difference (SMD): -0.41; 95% CI: -0.85, 0.02, I2 = 59%, low grade evidence]. Significant reductions were also seen for total cholesterol with saxagliptin versus metformin (MD: -0.15 mmol/L; 95% CI: -0.23, -0.08, I2 = 0%, very low grade evidence). Significant reductions in C-reactive protein (CRP) were seen for atorvastatin versus placebo (MD: -1.51 mmol/L; 95% CI: -3.26 to 0.24, I2 = 75%, very low-grade evidence). CONCLUSION: There were significant reductions in the lipid parameters when metformin, atorvastatin, saxagliptin, rosiglitazone and pioglitazone were compared with placebo or other agents. There was also a significant reduction of CRP with atorvastatin.

Extracellular Vesicle-Based Therapy for COVID-19: Promises, Challenges and Future Prospects.

The COVID-19 pandemic has become a serious concern and has negatively impacted public health and the economy. It primarily targets the lungs, causing acute respiratory distress syndrome (ARDS); however, it may also lead to multiple organ failure (MOF) and enhanced mortality rates. Hence, there is an urgent need to develop potential effective therapeutic strategies for COVID-19 patients. Extracellular vesicles (EVs) are released from various types of cells that participate in intercellular communication to maintain physiological and pathological processes. EVs derived from various cellular origins have revealed suppressive effects on the cytokine storm during systemic hyper-inflammatory states of severe COVID-19, leading to enhanced alveolar fluid clearance, promoted epithelial and endothelial recovery, and cell proliferation. Being the smallest subclass of EVs, exosomes offer striking characteristics such as cell targeting, being nano-carriers for drug delivery, high biocompatibility, safety, and low-immunogenicity, thus rendering them a potential cell-free therapeutic candidate against the pathogeneses of various diseases. Due to these properties, numerous studies and clinical trials have been performed to assess their safety and therapeutic efficacy against COVID-19. Hence, in this review, we have comprehensively described current updates on progress and challenges for EVs as a potential therapeutic agent for the management of COVID-19.

A review of therapeutic agents and Chinese herbal medicines against SARS-COV-2 (COVID-19).

The epidemic of pneumonia (COVID-19) caused by novel coronavirus (SARS-CoV-2) infection has been listed as a public health emergency of international concern by the World Health Organization (WHO), and its harm degree is defined as a global "pandemic". At present, the efforts of various countries focus on the rapid diagnosis and isolation of patients, as well as to find a treatment that can combat the most serious impact of the disease. The number of reported COVID-19 virus infections is still increasing. Unfortunately, no drugs or vaccines have been approved for the treatment of human coronaviruses, but there is an urgent need for in-depth research on emerging human infectious coronaviruses. Clarification transmission routes and pathogenic mechanisms, and identification of potential drug treatment targets will promote the development of effective prevention and treatment measures. In the absence of confirmed effective treatments, due to public health emergencies, it is essential to study the possible effects of existing approved antivirals drugs or Chinese herbal medicines for SARS-CoV-2. This review summarizes the epidemiological characteristics, pathogenesis, virus structure and targeting strategies of COVID-19. Meanwhile, this review also focus on the re-purposing of clinically approved drugs and Chinese herbal medicines that may be used to treat COVID-19 and provide new ideas for the discovery of small molecular compounds with potential therapeutic effects on novel COVID-19.

A Therapeutic Journey of Potential Drugs Against COVID-19.

Coronavirus disease (CoVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) scrambles the world by infecting millions of peoples all over the globe. It has caused tremendous morbidity, mortality and greatly impacted the lives and economy worldwide as an outcome of mandatory quarantines or isolations. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in the clinical treatment of COVID-19 patients in large-scale studies. Physicians and researchers throughout the world are working to understand the pathophysiology to expose the conceivable handling regimens and to determine the effective vaccines and/or therapeutic agents. Some of them re-purposed drugs for clinical trials which were primarily known to be effective against the RNA viruses including MERS-CoV and SARS-CoV-1. In the absence of a proven efficacy therapy, the current management use therapies based on antivirals, anti-inflammatory drugs, convalescent plasma, anti-parasitic agents in both oral and parenteral formulation, oxygen therapy, and heparin support. What is needed at this hour, however, is a definitive drug therapy or vaccine. Different countries are rushing to find this, and various trials are already underway. We aimed to summarize the potential therapeutic strategies as treatment options for COVID-19 that could be helpful to stop further spread of SARS-CoV-2 by affecting its structural components or modulation of immune response and discuss the leading drugs/vaccines, which are considered as potential agents for controlling this pandemic.

Drug Repurposing Strategy (DRS): Emerging Approach to Identify Potential Therapeutics for Treatment of Novel Coronavirus Infection.

Drug repurposing is also termed as drug repositioning or therapeutic switching. This method is applied to identify the novel therapeutic agents from the existing FDA approved clinically used drug molecules. It is considered as an efficient approach to develop drug candidates with new pharmacological activities or therapeutic properties. As the drug discovery is a costly, time-consuming, laborious, and highly risk process, the novel approach of drug repositioning is employed to increases the success rate of drug development. This strategy is more advantageous over traditional drug discovery process in terms of reducing duration of drug development, low-cost, highly efficient and minimum risk of failure. In addition to this, World health organization declared Coronavirus disease (COVID-19) as pandemic globally on February 11, 2020. Currently, there is an urgent need to develop suitable therapeutic agents for the prevention of the outbreak of COVID-19. So, various investigations were carried out to design novel drug molecules by utilizing different approaches of drug repurposing to identify drug substances for treatment of COVID-19, which can act as significant inhibitors against viral proteins. It has been reported that COVID-19 can infect human respiratory system by entering into the alveoli of lung via respiratory tract. So, the infection occurs due to specific interaction or binding of spike protein with angiotensin converting enzyme-2 (ACE-2) receptor. Hence, drug repurposing strategy is utilized to identify suitable drugs by virtual screening of drug libraries. This approach helps to determine the binding interaction of drug candidates with target protein of coronavirus by using computational tools such as molecular similarity and homology modeling etc. For predicting the drug-receptor interactions and binding affinity, molecular docking study and binding free energy calculations are also performed. The methodologies involved in drug repurposing can be categorized into three groups such as drug-oriented, target-oriented and disease or therapy-oriented depending on the information available related to quality and quantity of the physico-chemical, biological, pharmacological, toxicological and pharmacokinetic property of drug molecules. This review focuses on drug repurposing strategy applied for existing drugs including Remdesivir, Favipiravir, Ribavirin, Baraticinib, Tocilizumab, Chloroquine, Hydroxychloroquine, Prulifloxacin, Carfilzomib, Bictegravir, Nelfinavir, Tegobuvir and Glucocorticoids etc to determine their effectiveness toward the treatment of COVID-19.

Modalities and Mechanisms of Treatment for Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly throughout the world. Although COVID-19 has a relatively low case severity rate compared to SARS and Middle East Respiratory syndrome it is a major public concern because of its rapid spread and devastating impact on the global economy. Scientists and clinicians are urgently trying to identify drugs to combat the virus with hundreds of clinical trials underway. Current treatments could be divided into two major part: anti-viral agents and host system modulatory agents. On one hand, anti-viral agents focus on virus infection process. Umifenovir blocks virus recognizing host and entry. Remdesivir inhibits virus replication. Chloroquine and hydroxychloroquine involve preventing the whole infection process, including virus transcription and release. On the other hand, host system modulatory agents are associated with regulating the imbalanced inflammatory reaction and biased immune system. Corticosteroid is believed to be commonly used for repressing hyper-inflammation, which is one of the major pathologic mechanisms of COVID-19. Convalescent plasma and neutralizing antibodies provide essential elements for host immune system and create passive immunization. Thrombotic events are at high incidence in COVID-19 patients, thus anti-platelet and anti-coagulation are crucial, as well. Here, we summarized these current or reproposed agents to better understand the mechanisms of agents and give an update of present research situation.