First-in-class small molecule drugs in 2022.

2022 is the third year of the global COVID-19 pandemic, and its troubles on new drug discovery are gradually apparent. 37 new drugs were approved by the FDA's Center for Drug Evaluation and Research (CDER) last year, down from the peak of 50 new drug approvals in 2021. Notably, first-in-class drugs still occupy a dominant position this year, with a total of 21 drugs. Among them, 7 are first-in-class small molecule drugs. Although the total number of new drug approvals in 2022 sharply decreased, some first-in-class small molecule drugs were regarded as significant, including mitapivat, the first oral activator targeting the pyruvate kinase (PK);mavacamten, the first selective allosteric inhibitor targeting the myocardial beta myosin ATPase;deucravacitinib, the first deuterated allosteric inhibitor targeting the tyrosine kinase 2 (TYK2);and lenacapavir, the first long-acting inhibitor targeting the HIV capsid. Generally, the research of first-in-class drugs needs to focus on difficult clinical problems and can treat some specific diseases through novel targets and biological mechanisms. There are tremendous challenges in the research processes of new drugs, including biological mechanism research, target selection, molecular screening, lead compound identification and druggability optimization. Therefore, the success of first-in-class drugs development has prominent guidance significance for new drug discovery. This review briefly describes the discovery background, research and development process and therapeutic application of 3 firstin- class small molecule drugs to provide research ideas and methods for more first-in-class drugs.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.

Exosomes/EVs: BIOXOME: A NATURAL LIPOSOME MIMETIC AS DRUG DELIVERY SYSTEM

Background & Aim: Liposomes are spherical-shaped vesicles composed of one or more lipid bilayers. The ability of liposomes to encapsulate hydro- or lipophilic drugs allowed these vesicles to become a useful drug delivery system. Natural cell membranes, such as Bioxome, have newly emerged as new source of materials for molecular delivery systems. Bioxome are biocompatible and GMP-compliant liposome-like membrane that can be produced from more than 200 cell types. Bioxome self-assemble, with in-process self-loading capacity and can be loaded with a variety of therapeutic compounds. Once close to the target tissue, Bioxome naturally fuse with the cell membrane and release the inner compound. Orgenesis is interested in evaluating the potential of Bioxome as new drug delivery system for treatment of several diseases, including skin repair, local tumour or COVID19. Methods, Results & Conclusion(s): Bioxome were obtained from adipose- derived Mesenchymal Stem Cells, with a process of organic- solvent lipid extraction, followed by lyophilization and sonication assemblage. During the sonication process, Bioxome were charged or not with several cargos. Size distribution of empty Bioxome was detected by Particle Size Analyzer (NanoSight). Electron Microscopy (EM) was performed to assess Bioxome morphology. Lipid content was evaluated by electrospray ionization system. Dose response in vitro test on human lung fibroblasts treated or not with Bioxome encapsulating a specific cargo (API) against COVID19 were performed. NanoSight analysis showed that nanoparticle size in Bioxome samples ranged between 170+/-50 nm, with a concentration ranging between 109-1010+/-106 particles/mL. EM clearly showed the double phospholipid layers that composes the Bioxome. Stability study demonstrated that Bioxome are stable in size and concentration up to 90 days at +4Cdegree or even at RT. No change in size between encapsulated Bioxome with small size (~340 Da) cargo vs empty Bioxome was observed up to 30 days storage. Lipidomic analysis approach revealed that the yield of lipids and their composition are satisfactory for a therapeutic product using Bioxome. Lastly, in the in vitro model of COVID19, Bioxome encapsulating API effectively saved cells from death (20x vs untreated cells) and at lower doses of API than these of non-encapsulated cargo (0.005 microM vs 0.1 microM). Bioxome seems to be an excellent candidate for liposome mimetic tool as drug delivery system for targeting specific organs and diseases treatment.Copyright © 2023 International Society for Cell & Gene Therapy

EXPERIENCE WITH TIXAGEVIMAB AND CILGAVIMAB (EVUSHELD) IN 86 RHEUMATIC PATIENTS UNDERGOING ANTI-B CELL THERAPY WITH RITUXIMAB.

The problem of prevention of coronavirus disease 2019 (COVID-19) in patients with immune-mediated inflammatory rheumatic diseases (IMRD) remains highly relevant. The presence of IRD is associated with a high risk of disease and severe course of COVID-19 during immunosuppressive treatment, primarily anti-B cell therapy with rituximab (RTX), and a low level of post-vaccination response in such patients. A new strategy for the prevention and treatment of COVID-19 are virus-neutralizing monoclonal antibodies to coronavirus;currently, combined long-acting monoclonal antibodies tixagevimab and cilgavimab (Evusheld) are registered for prevention in the world and the Russian Federation. . Tixagevimab and cilgavimab (TC) show neutralizing activity against SARS-CoV-2, including the Omicron strain, primarily its variants BA.4, BA.5, BA.2.75 ("Centaur"). Objective - to evaluate the efficacy and safety of TC for pre-exposure prophylaxis of COVID-19 in rheumatic patients receiving RTX, based on a prospective observational study. Materials and methods. The main group included 86 patients with various IMRD receiving RTX: 50 of them had ANCA-associated systemic vasculitis (AAV), 15 - rheumatoid arthritis, 9 - Sjogren's syndrome (SS), 4 - IgG4-related disease, 3 - systemic lupus erythematosus (SLE), 3 - dermatomyositis (DM), 2 - systemic scleroderma (SSD). Median age was 59 (19-82) years;male: female ratio - 1:1,8. From March 26 to August 30 2022, patients received a single intramuscular injection of TC in a total dose of 300 mg, mainly after RTX (in 52% of cases, in 28% on the next day after RTX). The control group included 42 patients with AAV (median age - 45 (35-71) years;male: female ratio - 1:1), also treated with RTX, who did not receive pre-exposure prophylaxis of TC. The duration of observation was 7 months, until November 1 2022. At this time, 98% of confirmed cases of coronavirus in the Russian Federation were Omicron. A telephone and/or online survey of patient has been conducted to detect cases of COVID-19 and adverse reactions. Results. In the TC group, confirmed coronavirus infection have been detected in 17 (20%) patients (AAV - 10, SS - 3, SSD - 2, SLE - 1, DM - 1), with fever in 7 (8%), only in one case hospitalization was required (lung damage was not detected in computed tomography), in two cases, according to CT mild lung damage (CT 1-2), there were no deaths. Good TC's tolerability was noted, signs not associated with COVID-19 or progression of IMRD after administration of TC were observed in 8 (9%) patients (GPA - 3 MPA - 1, RA - 2, SLE - 1, IgG4-related disease - 1), adverse reactions definitely associated with the use of TC were not found. The most serious event not associated with coronavirus infection was the progression of polyneuropathy in a patient with RA. In the control group, 3 (7%) patients were diagnosed with COVID-19, one with severe lung injury (CT 3, pulmonary embolism) and death. Conclusions. The data of clinical studies and our own clinical experience evidence the effectiveness of the use of a combination of long-acting monoclonal antibodies TC (Evusheld), registered for indications for pre-exposure prophylaxis and treatment of COVID-19. Patients with IMRD treated with RTX have a favorable safety profile of TC. The introduction of virus-neutralizing monoclonal antibodies, a new drug class for the prevention and treatment of infectious diseases, opens significant prospects for improving the prognosis of patients with IRD.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

Cell Therapy: cGMP Facilities and Manufacturing: Second Edition

This new edition presents a fully-updated and expanded look at current Good Manufacturing Practice (cGMP) for cell therapy products. It provides a complete discussion of facility design and operation including details specific to cord blood banking, cell processing, vector production and qualification of a new facility. Several chapters cover facility infrastructure including cleaning and maintenance, vendor qualification, writing a Standard Operating Procedure, staff training, and process validation. The detailed and invaluable product information covers topics like labelling, release and administration, transportation and shipment, et al. Further chapters cover relevant topics like writing and maintaining investigational new drug applications, support opportunities in North America and the European Union, commercial cell processing and quality testing services, and financial considerations for academic GMP facilities. A chapter on future directions rounds out Cell Therapy: cGMP Facilities and Manufacturing making it essential reading for any cell therapy professional involved in the development, use, or management of this type of facility. © Springer Nature Switzerland AG 2009, 2022, Corrected Publication 2022.

First-in-class small molecule drugs in 2022

2022 is the third year of the global COVID-19 pandemic, and its troubles on new drug discovery are gradually apparent. 37 new drugs were approved by the FDA's Center for Drug Evaluation and Research (CDER) last year, down from the peak of 50 new drug approvals in 2021. Notably, first-in-class drugs still occupy a dominant position this year, with a total of 21 drugs. Among them, 7 are first-in-class small molecule drugs. Although the total number of new drug approvals in 2022 sharply decreased, some first-in-class small molecule drugs were regarded as significant, including mitapivat, the first oral activator targeting the pyruvate kinase (PK);mavacamten, the first selective allosteric inhibitor targeting the myocardial beta myosin ATPase;deucravacitinib, the first deuterated allosteric inhibitor targeting the tyrosine kinase 2 (TYK2);and lenacapavir, the first long-acting inhibitor targeting the HIV capsid. Generally, the research of first-in-class drugs needs to focus on difficult clinical problems and can treat some specific diseases through novel targets and biological mechanisms. There are tremendous challenges in the research processes of new drugs, including biological mechanism research, target selection, molecular screening, lead compound identification and druggability optimization. Therefore, the success of first-in-class drugs development has prominent guidance significance for new drug discovery. This review briefly describes the discovery background, research and development process and therapeutic application of 3 firstin- class small molecule drugs to provide research ideas and methods for more first-in-class drugs.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.

Antimicrobial Activity: Different Mechanistic Elucidation of Antibacterial, Antiviral, Antifungal & Antialgae Agents

In recent days, the increasing number of microbes and their increasing resistance power against conventional drugs have led to enormous worldwide mortalities, hence they pose a great threat to human health. The modern era is already going through the threat of COVID-19, also caused by one of those microbes called the virus. In order to get a clear understanding, all the microbes have been classified in certain types. Nowadays, to develop new alternative antimicrobial medicines, scientists must acquire clarity about the responsible functional groups of different conventional drugs with proper mechanistic elucidation on different types of microbes. This information not only clarifies the functionalities and properties responsible for exhibiting antimicrobial effects, but also facilitates the idea of new drug development through proper functional group incorporation or modification. These modifications increase the efficacy of antimicrobial drugs as well as their activity and water solubility. In this review, my focus will majorly be on the four main types of microbes and their possible mechanistic elucidation of commonly used antibiotics and alternative antimicrobial medicines discovered till now. I thank the Science and Engineering Research Board (SERB), Council of Scientific and Industrial Research (CSIR), and Government of India for my fellowship and research grants during my Ph.D in Indian Institute of Science Education and Research, Kolkata and Postdoctoral journey in the University of Burdwan. I acknowledge Prof. Bimalendu Ray (Chemistry department, The University of Burdwan), Prof. Priyadarsi De, (Polymer Research Centre, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata), Prof. Punyasloke Bhadury (Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata), Dr. Anwesha Ghosh (Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata) for many helpful discussions and laboratory use.Copyright © 2023 are reserved by International Journal of Pharmaceutical Sciences and Research.

Convalescent Plasma Treatment of Severe Covid-19 Cases in the Bronx, Ny

Junior Physician Investigator Award Recipient Purpose of study Severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2) is the causative agent of the Coronavirus disease 2019 (COVID-19) pandemic. Convalescent plasma obtained from recovered persons was used for previous respiratory pandemics. Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) was proposed as an option that may hold promise as treatment for COVID-19. Our aim was to retrospectively evaluate the efficacy of CCP treatment of patients with severe to life-threatening COVID-19 hospitalized at Montefiore Medical Center (MMC) in the Bronx, NY between April 13 to May 4, 2020. Methods used We administered CCP as part of the Mayo Clinic expanded access investigational new drug (IND) program for hospitalized patients. We compared the mortality and clinical outcome of 73 patients with COVID-19 who received 200 mL of CCP with a Spike protein IgG titer >=1:2,430 (median 1:47,385) within 72 hours of admission to 1:1 propensity score-matched controls. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroids, and anticoagulation use (figure 1). We additionally measured Spike protein IgG and neutralizing antibody titer in CCP and pre- and post-transfusion Spike protein IgG, IgM and IgA titer in CCP recipients. The primary outcome was all-cause mortality at day 28 post-CCP. The secondary outcomes were improvement in oxygenation status or mortality at day 28 post-CCP. Exploratory outcomes were associations between pre-CCP SARS-CoV-2 antibody titers and mortality at day 28. Summary of results There was no difference in mortality or oxygenation between CCP recipients and controls at day 28. When stratified by age, compared to matched controls, CCP recipients < 65 years had 4-fold lower mortality and 4-fold lower deterioration in oxygenation or mortality at day 28 (figure 2, 3). There was no association between CCP IgG or neutralizing antibody titer and clinical outcome. For CCP recipients, pre-transfusion Spike protein IgG, IgM and IgA titers were associated with mortality at day 28 in univariate analyses but not in multivariable analyses. Pre-transfusion Spike protein IgG titer was significantly correlated with Ddimer and detected viral load measured by cycle threshold (Ct) value of nasopharyngeal SARS-CoV-2 reverse-transcriptase- polymerase-chain-reaction (figure 4). No adverse effects of CCP were observed. Conclusions We report that CCP administration within 72 hours of hospitalization demonstrated a possible signal of reduced mortality in patients < 65 years. Pre-transfusion IgG titer may be a proxy for disease severity that may be useful in identifying those who are more likely to respond to CCP. Data from controlled trials is needed to validate this finding and establish the effect of ageing on CCP efficacy. (Figure Presented).

Structure-Based Identification and Analysis of Viral Protease Inhibitors Targeting SARS CoV-2 Virus Replication

The re-emergence of SARS-CoV, known as SARS-CoV-2, has proven extremely infectious that has infected a huge population worldwide. SARS-CoV-2 genome is translated into polyproteins that is processed by virus-specific protease enzymes. 3CLprotease is named as the main protease (Mpro) enzyme that cleaves nsp4 to nsp16. This crucial role of Mpro makes this enzyme a prime and promising antiviral target. Till date, there is no effective commercially available drug against COVID-19 and launching a new drug into the market is a complicated and time-consuming process. Therefore, drug repurposing is a new but familiar approach to reduce the time and cost of drug discovery. We have used a high-throughput virtual screening approach to examine FDA approved library, natural compound library, and LOPAC 1280 (Library of Pharmacologically Active Compounds, Sigma-Aldrich, St. Louis, MO) library against Mpro. Primary screening identified potential drug molecules for the target, among which ten molecules were studied further using biophysical and biochemical techniques. SPR was used to validate the binding of inhibitors to purified Mpro and using FRET-based biochemical protease assay these inhibitors were confirmed to have Mpro inhibitory activity. Based on the kinetic studies, the antiviral efficacy of these compounds was further analysed by cell-culture based antiviral assays. Four out of ten molecules inhibited SARS-CoV-2 replication in Vero cells at a concentration range of 12.5 to 50 muM. The antiviral activity was evaluated by RT-PCR assay and TCID50 experiments. The co-crystallization of Mpro in complex with inhibitor for determining their structures is being carried out. Collectively, this study will provide valuable mechanistic and structural insights for development of effective antiviral therapeutics against SARS-CoV-2.

THE ROLE OF NEUTROPHIL EXTRACELLULAR TRAPS (NETs) IN THE IMMUNOPATHOGENESIS OF SEVERE COVID-19: POTENTIAL IMMUNOTHERAPEUTIC STRATEGIES REGULATING NET FORMATION AND ACTIVITY.

The role of neutrophil granulocytes (NG) in the pathogenesis of COVID-19 is associated with the NG recruitment into inflammatory foci, activation of their functions and enhanced formation of neutrophil extracellular networks (NETs). In this review, we analyzed a large body of scientific literature devoted to the features of developing NETs, their role in the COVID-19 pathogenesis, a role in emerging immunothrombosis, vasculitis, acute respiratory distress syndrome, cytokine storm syndrome, and multi-organ lesions. Convincing data are presented clearly indicating about a profound role of NETs in the COVID-19 immunopathogenesis and associated severe complications resulting from intensified inflammation process, which is a key for the course of SARS-CoV-2 virus infection. The presented role of NGs and NETs, along with that of other immune system cells and pro-inflammatory cytokines, is extremely important in understanding development of overactive immune response in severe COVID-19. The scientific results obtained available now allow to identify an opportunity of regulatory effects on hyperactivated NGs, NETosis at various stages and on limiting a negative impact of pre-formed NETs on various tissues and organs. All the aforementioned data should help in creating new, specialized immunotherapy strategies designed to increase the odds of survival, reduce severity of clinical manifestations in COVID-19 patients as well as markedly reduce mortality rates. Currently, it is possible to use existing drugs, while a number of new drugs are being developed, the action of which can regulate NG quantity, positively affect NG functions and limit intensity of NETosis. Continuing research on the role of hyperactive NG and NETosis as well as understanding the mechanisms of regulating NET formation and restriction in severe COVID-19, apparently, are of high priority, because in the future the new data obtained could pave the basis for development of targeted approaches not only for immunotherapy aimed at limiting education and blocking negative effects already formed NETs in severe COVID-19, but also for immunotherapy, which could be used in combination treatment of other netopathies, primarily autoimmune diseases, auto-inflammatory syndromes, severe purulent-inflammatory processes, including bacterial sepsis and hematogenous osteomyelitis.Copyright © 2023 Saint Petersburg Pasteur Institute. All rights reserved.

Chemoinformatics approach to design and develop vanillin analogs as COX-1 inhibitor

Background: Coronary Heart Disease (CHD), commonly known as the silent killer, impacted the severity of COVID-19 patients during the pandemic era. Thrombosis or blood clots create the buildup of plaque on the coronary artery walls of the heart, which leads to coronary heart disease. Cyclooxygenase 1 (COX-1) is involved in the production of prostacyclin by systemic arteries;hence, inhibiting the COX-1 enzyme can prevent platelet reactivity mediated by prostacyclin. To obtain good health and well-being, the research of discovery of new drugs for anti-thrombotic still continue. Objective(s): This study aims to predict the potential of 17 compounds owned by the vanillin analog to COX-1 receptor using in silico. Method(s): This research employed a molecular docking analysis using Toshiba hardware and AutoDock Tools version 1.5.7, ChemDraw Professional 16.0, Discovery Studio, UCSF Chimera software, SWISSADME and pKCSM, a native ligand from COX-1 (PDB ID: 1CQE) was validated. Result(s): The validation result indicated that the RMSD was <2 A. The 4-formyl-2-methoxyphenyl benzoate compound had the lowest binding energy in COX-1 inhibition with a value of-7.70 A. All vanillin derivatives show good intestinal absorption, and the predicted toxicity indicated that they were non-hepatotoxic. All these compounds have the potential to be effective antithrombotic treatments when consumed orally. Conclusion(s): In comparison to other vanillin derivative com-pounds, 4-formyl-2-methoxyphenyl benzoate has the lowest binding energy value;hence, this analog can continue to be synthesized and its potential as an antithrombotic agent might be confirmed by in vivo studies.Copyright © the Author(s), 2023.

Year 2022 in review - Cardiac anesthesia and postoperative care.

Cardiac anesthesia and postoperative care in cardiac surgery have their specifics, which differ from other specialties. The last two years marked by the COVID-19 pandemic were associated with a slowdown in elective cardiac surgery. Currently, the number of procedures is increasing again. New drugs are tested, new guidelines are published, innovative and hybrid procedures are performed, with the goal of reducing invasiveness for the patients. The aim of this review is to present readers with the important outputs of publications related to cardiac anesthesia, postoperative care in cardiac surgery, and the use of extracorporeal circulatory support over the past year.Copyright © 2022, Czech Medical Association J.E. Purkyne. All rights reserved.

Anaphylaxis to trometamol excipient in Moderna COVID-19 vaccine: A case report

Case report The first approved COVID-19 vaccines include BNT162B2 Pfizer-BioNTech and mRNA-1273 Moderna mRNA vaccines. Some severe allergic reactions to these vaccines have been report, and even though there is a lack of robust evidence, IgE-mediated hypersensitivity to excipients may be the cause of several. The excipient polyethylene glycol (PEG) is present in both, whilst Moderna further contains trometamol (or tromethamine), a buffer additive present in drug formulations and contrast media. We report the case of a 40 year-old woman, with controlled allergic rhinitis and asthma, who was referred to our Immunoallergology Department due to an anaphylactic reaction to Moderna COVID-19 vaccine. She described an episode of cervical and facial pruritus 5 minutes after receiving the first dose of vaccine, which rapidly evolved to generalized urticaria. She was promptly given intravenous (IV) clemastine with improvement of symptoms. However, 1h later she developed respiratory symptoms (dry cough, shortness of breath and wheezing). IV hydrocortisone was also given, and the patient was kept under medical supervision for 6h, after which she was discharged home. The following day, she had urticaria that resolved with oral deflazacort (60 mg). She denies exercise practice, alcohol consumption or outset of new drugs prior to vaccination. During investigation, the patient described two similar reactions in the past, 5 minutes after the administration of trometamol-containing contrast media (10 years before with an iodinated contrast and 2 years ago with a gadolinium contrast, both with trometamol). A week after the reaction all laboratory evaluation were within normal limits, including tryptase level. Skin tests were performed, 2 months after, with contrast media that contain trometamol (iopromide, iomeprol, iodixanol, ioversol, gadobutrol) and that do not (ioxitalamate, amidotrizoate, gadoterate meglumine), in accordance with the EAACI/ENDA guidelines. Iopromide and iodixanol were positive on intradermal testing (1:10 dilution), suggesting trometamol as the culprit excipient. She was advised not to receive the 2nd dose of Moderna vaccine. She received Pfizer-BioNTech vaccine at the hospital, without any reactions. This case demonstrates that an IgE-mediated reaction to trometamol may be an underlying mechanism for immediate hypersensitivity to mRNA Moderna vaccine. The risk of an allergic reaction to it increases when a previous history of hypersensitivity to contrast media exists.

Antiviral Activity of Medicinal Plants against Human Coronavirus: a systematic scoping review of and experimentations.

OBJECTIVE: To investigate the and studies of natural compounds and medicinal plants with anti-coronavirus activity. METHODS: A systematic review was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Animal Research: Reporting of experiments guidelines to find data for medicinal plants and natural products effective against human coronaviruses in or studies. Studies published up to September 6, 2020 were included. Studies ( or ) reporting the effect of medicinal plants and natural products or their derivatives on human coronavirus were included RESULTS: Promising anti-coronavirus effects are seen with different herbal compounds like some diterpenoids, sesquiterpenoids, and three compounds in tea with 3CLpro inhibiting effect of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV); Hirsutenone, Six cinnamic amides and bavachinin are PLpro inhibitors and Tanshinones are active on both 3CLpro and PLpro. Some flavonoid compounds of Citrus fruits act on Immun-oregulation and target angiotensin-converting enzyme 2 which is used by SARS-COV for entry. Virus helicase is possibly inhibited by two compounds myricetin and scutellarein. CONCLUSION: This review shows that complementary medicine have the potential for new drug discovery against coronavirus. Further research is needed before definitive conclusions can be made concerning the safety and efficacy of the use of these medicinal plants.

A New Threat to Mankind: COVID 19-All You Need to Know

The devastating COVID 19 Pandemic, which set an outbreak by the end of 2019, has led the whole world into an alarming situation. So, considering the need of the time, we decided to put some light on the important aspects of the pandemic. Here we have discussed the different coronaviruses which can affect humans and also how this new coronavirus is different than the previously identified coronaviruses. In general, SARS CoV-2 is elaborated along with origin, virology, and transmission. The disease (COVID 19) is studied and briefed for its prognosis and symptoms and as to how the detection of the infection is done. As we know that we have not found any full proof solution for this outbreak but can fight it to save mankind, the need for new drug development and the current scenario on available options is discussed along with how the world is combatting the situation to stop its spread. Also, the common myths among the public about the disease are busted here. The paper is concluded with the current statistics of the outbreak. The purpose of this paper is to provide the general public with some know-how of the pandemic.Copyright © 2021 Bentham Science Publishers.

Therapeutic Options for the Treatment of 2019-Novel Coronavirus in India: A Review

Purpose: As of, from 30th Jan to 31st May, 2020, more than 182,143 confirmed cases were reported in India along with 86,984 recovered cases and 5164 deceased cases of COVID-19. More than 53 countries are also affected with this pandemic virus. However, the lack of specific drugs to prevent/treat this pandemic disease is a major problem in this current scenario. In this re-gard, this systemic review was conducted to identify the therapeutic approaches and researches, which are ongoing in India against COVID-19. Method(s): We had screened Google Scholar database with the keywords nCoV, corona virus in In-dia, effect of SARS-CoV-2 in India, 2019-nCoV, treatment pattern in India for nCoV and therapy used to treat nCoV in India. In the final review, we had included a total of 49 articles. Result(s): As a result we had found that the Indian Council of Medical Research and NIH have giv-en a standard guideline of Hydroxychloroquine and other antiviral drugs for nCoV, and also there are various researches going on related to nCoV treatment like, chemicals from natural products, herbs and spices commonly used in India, combination therapy of lopinavir and ritonavir, ultra-vio-let radiation therapy, molecular dynamic (MD) simulations of molecules for vaccine preparation, Convalescent plasma transfusion (CPT) therapy and many more. Conclusion(s): New drugs and therapy are in the premature stage for this hazardous pandemic. We need more time to gain the detailed knowledge of the life cycle of the nCoV, which can speed up the drug/vaccine development process against nCoV.Copyright © 2022 Bentham Science Publishers.

The Potential Impact of Ayurvedic Traditional Bhasma on SARS-CoV-2-Induced Pathogenesis

The mass casualties caused by the delta variant and the wave of the newer "Omicron" variant of SARS-COV-2 in India have brought about great concern among healthcare officials. The government and healthcare agencies are seeking effective strategies to counter the pandemic. The application of nanotechnology and repurposing of drugs are reported as promising approaches in the management of COVID-19 disease. It has also immensely boomed the search for productive, re-liable, cost-effective, and bio-assimilable alternative solutions. Since ancient times, the traditional-ly employed Ayurvedic bhasmas have been used for diverse infectious diseases, which are now employed as nanomedicine that could be applied for managing COVID-19-related health anomalies. Like currently engineered metal nanoparticles (NPs), the bhasma nanoparticles (BNPs) are also packed with unique physicochemical properties, including multi-elemental nanocrystalline compo-sition, size, shape, dissolution, surface charge, hydrophobicity, and multi-pathway regulatory as well as modulatory effects. Because of these conformational and configurational-based physico-chemical advantages, Bhasma NPs may have promising potential to manage the COVID-19 pandemic and reduce the incidence of pneumonia-like common lung infections in children as well as age-related inflammatory diseases via immunomodulatory, anti-inflammatory, antiviral, and adju-vant-related properties.Copyright © 2023 Bentham Science Publishers.

Potential of Hesperidin in the Medicinal Field

Hesperidin has gained major interest recently due to the outbreak of COVID-19. The traction has led to more research being conducted on the compound hesperidin. Recent studies have shown its anti-inflammatory and anti-viral attributes, which have beneficial effects on severe acute respiratory syndrome (SARS-CoV-2). Hesperidin has also shown unique effects on the protein of SARS-CoV-2, which lead to a good preventative measure for SARS-CoV-2. Hesperidin also causes a suppression of appetite, which helps to combat obesity through the release of cholecystokinin. Furthermore, hesperidin has shown cardioprotective properties, which cause an increase in plasma high-density lipoprotein levels and a decrease in plasma low-density lipoprotein levels. Hesperidin is also used in combination with the Japanese herb Rikkunshito, which has shown potential in a discovery of a new drug for gastrointestinal motility as hesperidin can depolarize pacemaker potential in interstitial cells of Cajal (ICC). The chemo-preventive effects of hesperidin are caused by its antioxidant effect, which may prevent tissue necrosis due to oxidative stress. The photo-protective effect of hesperidin can reduce the damage to the skin caused by UV rays. Hesperidin also possesses wound-healing properties.Copyright © 2023 Bentham Science Publishers.

Support for patients with MBC

Over the last decade we have witnessed rapid advances in the treatment of patients with metastatic breast cancer (MBC) with seminal discoveries in cancer biology, correlative biomarkers and clinical trials leading to multiple new drug approvals. While these milestones have improved survival, the science of survivorship in this population is just beginning. The diagnosis of MBC is life-changing and requires individualized and multidisciplinary support. The NCI defined the areas of epidemiology and surveillance, symptom management, psychosocial research, health-care delivery, and health behaviors as necessary fields to advance the state of the science in advanced cancer survivors. A multifaceted program addressing these domains is needed to assess MBC patients and their unique and ever-changing needs. With input from patients and providers, program components should include: therapeutic clinical trials, multidisciplinary specialty care, individualized patient navigation, peer support, continuing education, and patient reported outcome (PRO) collection to support patients living with MBC. Input for a program for MBC patients can be guided by a multidisciplinary steering committee in which patient advocates are a major voice. Patients can provide insight into what works for them, and what they are facing may be very different from the experience of an early-stage breast cancer patient. Clinical trials designed to advance the current scientific knowledge of breast cancer treatment are essential to patients living longer, more fulfilled lives with MBC. Clinical trials may include systemic therapy, local therapies such as surgery and radiation for MBC patients, side-effect management and quality of life (may put elsewhere). A comprehensive systemic therapy portfolio should include all biological subtypes as well as recommended treatment options (hormonal therapy, targeted therapy, chemotherapy, and immunotherapy). Multidisciplinary care is necessary to diagnose and treat any condition the MBC patient may encounter and is essential in providing quality care. Comorbidities and debilitating side effects arising from cancer treatment are known to be associated with inferior outcomes. MBC patients may experience lack of familiarity of some providers with novel MBC cancer treatment, side effects, and interactions of their cancer treatment with non-cancer conditions and treatment. With the increasing life expectancy of MBC patients, it is important to manage the medical comorbidities in coordination with the MBC patient's cancer treatment. Integrative Medicine helps support the quality of life of patients through providing clinical modalities such as stress management, yoga, meditation, acupuncture, massage and lifestyle counseling. Supportive care helps support cancer related fatigue and sleep challanges, geriatrics and hospice and palliative care for advanced cancer patients. The role of navigation for MBC patients is unique and should be designed to support the patient's many individual needs. Navigation requires assessment of individual knowledge deficit, coordination of care challenges, internal resource utilization, cultural requests, and emotional health. Navigation should also address the patient's financial and disability questions, medication assistance, symptom management, advanced care planning and goals of care discussions. Additional items to be discussed during navigation visits include primary care provider utilization, COVID-19 vaccination, illness and medication questions, and other patient questions as they arise. A comprehensive registry of MBC patient's medical records and histories will assist researchers in designing future therapeutic and quality of life clinical trials. The categories of patient demographics, clinical variables, pathological variables, treatment variables, outcomes of MBC, and PROs will create a robust registry. A comprehensive patient registry can create a rich database which can guide and inspire future innovative research. Peer support through support groups and peer-to-peer matching s pivotal to MBC patients finding and utilizing their patient voice, emotionally supporting each other and learning from other's similar experiences. Connection between patients and the creation of a community of survivors can empower patients to positively impact their care through self-advocacy and self-efficacy. Continuing patient education is also essential to providing quality cancer care. The format of a weekly virtual education webinars are helpful in creating an engaged patient community and a platform to disseminate educational resources in a reoccurring digestible format. Frequent educational webinars covering a wide variety of topics can positively influence patient interactions with their healthcare providers and influence how patients living with MBC view their own cancer experience. Educational webinars provide opportunities for patients to connect with subject matter experts, other patients like themselves, and share information with their family and friends. Informed patients can discuss and ask questions more confidently with their health care providers about information and services presented during the educational webinars. The symptom profile of patients living with MBC are impacted by numerous variables such as disease burden, treatment plan, comorbidities, supportive regimen etc. The collection of PROs has been shown to improve patient satisfaction with his/her care, improve quality of life, decrease emergency room visits and hospitalizations, and increased overall survival. The routine measurement and management of MBC patients' symptoms has been found to be integral in providing comprehensive cancer treatment. The collection of PROs improves patient and provider communication and elicits the outcome to symptoms that matter most to each patient. Patients diagnosed with MBC are living longer because of the recent advancements in therapeutic treatments. A multifaceted and comprehensive program consisting of therapeutic clinical trials, multidisciplinary specialty care, individualized patient navigation, peer support, continuing education, and PROs collection is integral to fully support patients living with MBC.

A study of new drug approval pattern of a Southeast Asian developed country from 2017 to 2021

Background: The pattern of new drug approval is changing across the world as shown by the study using Center for Drug Evaluation and Research and European Medicines Agency data in US and UK with more drug approval for anti-cancer and immunomodulator drugs. There is a need to generate similar database for developed South East Asian countries too. Aims and Objectives: This study was conducted for one such country-Singapore for the new drug approval pattern of last 5 years (2017-2021). Material(s) and Method(s): This was a pharmacoepidemiological study, in which government drug regulatory website data available in public domain was searched. The new drug approval data were classified according to active ingredient, drug approval date, new drug application category, indication of drugs, and World Health Organization Anatomic Thoracic Classification. Result(s): In this study, 418 new drug approvals were found in last 5 years in Singapore. From this maximum, drug approvals were given to anti-neoplastic and immunomodulator category drugs. In anti-neoplastic category new drugs approval few examples were Trastuzumab deruxtecan and Tucatinib for breast cancer therapy and Tepotinib and Capmatinib for non-small cell lung cancer therapy. Conclusion(s): This study shows that drug development in anti-cancer drug and immunomodulator is significant in Singapore. This trend is quite matching with other country such as US and UK.Copyright © 2023 Priti Solanky, et al.