Pharmacokinetic evaluation of drug-drug interactions in the treatment of COVID-19.

Objective: The COVID-19 pandemic, which started in Wuhan, China and affected the whole world, still represents a unique global challenge with its contagiousness and lethality. The symptoms of COVID-19 patients may differ depending on the severity of the disease. According to the report published by the Ministry of Health Coronavirus Research Advisory Board on the diagnosis, treatment and control of COVID-19, drug combination therapy (hydroxychloroquine, lopinavir / ritonavir and favipiravir) is recommended by health authorities. Drug-drug interaction is a possible situation as a result of simultaneous use of these drugs, which are metabolized by cytochrome P 450 enzymes (CYP), which are mostly found in the liver, with some other drugs. In this review, we aimed to show the pharmacokinetic drug-drug interactions of the drugs used in the treatment of COVID-19, especially by indicating the metabolism pathways. Result and Discussion: The COVID-19 pandemic adversely affects social life, economic and financial markets worldwide. Appropriate treatment protocols are of great importance but taking drug-drug interactions into account in treatment practices prevents unwanted results in patient treatment.Copyright © 2021 University of Ankara. All rights reserved.

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.

A substrate for a cell free in vitro assay system to screen drugs targeting trypsin like protease-based cleavage of SARS-CoV-2 spike glycoprotein and viral entry.

Host proteases trypsin and trypsin-like proteases have been reported to facilitate the entry of coronavirus SARS-CoV-2 in its host cells. These protease enzymes cleave the viral surface glycoprotein, spike, leading to successful cell surface receptor attachment, fusion and entry of the virus in its host cell. The spike protein has protease cleavage sites between the two domains S1 and S2. Since the cleavage site is recognized by the host proteases, it can be a potential antiviral therapeutic target. Trypsin-like proteases play an important role in virus infectivity and the property of spike protein cleavage by trypsin and trypsin-like proteases can be used to design assays for screening of antiviral candidates against spike protein cleavage. Here, we have documented the development of a proof-of-concept assay system for screening drugs against trypsin/trypsin-like proteases that cleave spike protein between its S1 and S2 domains. The assay system developed uses a fusion substrate protein containing a NanoLuc luciferase reporter protein, the protease cleavage site between S1 and S2 domains of SARS-CoV-2 spike protein and a cellulose binding domain. The substrate protein can be immobilized on cellulose via the cellulose binding domain of the substrate. When trypsin and trypsin-like proteases cleave the substrate, the cellulose binding domain remain bound to the cellulose and the reporter protein is dislodged. Reporter assay using the released reporter protein is the read out of the protease activity. We have demonstrated the proof-of-concept using multiple proteases like trypsin, TMPRSS2, furin, cathepsin B, human airway trypsin and cathepsin L. A significant increment in fold change was observed with increasing enzyme concentration and incubation time. Introduction of increasing amounts of enzyme inhibitors in the reaction reduced the luminescent signal, thus validating the assay. Furthermore, we used SDS-PAGE and immunoblot analyses to study the cleavage band pattern and re-confirm the cleavage for enzymes tested in the assay. Taken together, we have tested an in-vitro assay system using the proposed substrate for screening drugs against trypsin like protease-based cleavage of SARS-CoV-2 spike glycoprotein. The assay system can also be potentially used for antiviral drug screening against any other enzyme that might cleave the used cleavage site.

Analytical and biomedical applications of microfluidics in traditional Chinese medicine research

Traditional Chinese medicine (TCM) has significant benefits in the prevention and treatment of diseases due to its unique theoretical system and research techniques. However, there are still key issues to be resolved in the full interpretation and use of TCM, such as vague active compounds and mechanism of action. Therefore, it is promising to promote the research on TCM through innovative strategies and advanced cutting-edge technologies. Microfluidic chips have provided controllable unique platforms for biomedical applications in TCM research with flexible composition and large-scale integration. In this review, the analysis and biomedical applications of microfluidics in the field of TCM are highlighted, including quality control of Chinese herbal medicines (CHMs), delivery of CHMs, evaluation of pharmacological activity as well as disease diagnosis. Finally, potential challenges and prospects of existing microfluidic technologies in the inheritance and innovation of TCM are discussed.Copyright © 2022 Elsevier B.V.

Safety profile assessment of drug products used for the pathogenetic treatment of COVID-19.

Objective. To review and summarize literature data in studies of safety of the drug products used for the pathogenetic treatment of COVID-19. Materials and methods. As the first stage of monitoring the drug's safety, which are used in the treatment of COVID-19 in Russia, a systematic review of studies of the drug's safety profiles was carried out: Mefloquine, hydroxychloroquine, azithromycin, lopinavir/ritonavir, favipiravir, tocilizumab, olokizumab, baricitinib in the international databases Medline, PubMed, ClinicalTrials.gov and Cochrane Library for the period 2019-2021. Results. The review included 51 articles that met the selection criteria. Based on the results of the review, it can be concluded that the safety profile (frequency, severity and severity) of most drugs repurposed for COVID-19 corresponds to those for the registered indications. At the same time, according to world experience, there is an increase in the number of reports of adverse drug reactions of hydroxychloroquine and azithromycin, which is provoked by the active use of these drugs for combination therapy. Conclusions. According to the literature, a high incidence of adverse events was noted in hydroxychloroquine, chloroquine and azithromycin. Subsequent analysis and comparison of the safety profiles of hydroxychloroquine, chloroquine and azithromycin with data from the national automated information system (AIS) database of Roszdravnadzor is a necessary component of effective and safe pharmacotherapy for COVID-19.Copyright © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Medicinal bismuth: Bismuth-organic frameworks as pharmaceutically privileged compounds

Historically organometallic compounds have been used to cure certain diseases with limited applications. Although bismuth belongs to the category of heavy metals, many of its derivatives have found applications in modern drug discovery research, mainly because of its low toxicity and higher bioavailability. Being an eco-friendly mild Lewis acid, compounds having bismuth as a central atom are capable of binding several proteins in humans and other species. Bismuth complexes demonstrated antibacterial potential in syphilis, diarrhea, gastritis, and colitis. Apart from antibacterial activities, bismuth compounds exhibited anticancer, antileishmanial, and some extent of antifungal and other medicinal properties. This article discusses major synthetic methods and pharmacological potentials of bismuth complexes exhibiting in vitro activity to significant clinical performance in a systematic and timely manner.Copyright © 2022 Elsevier Ltd

Synthesis of new 3-(4-methyl-2-arylthiazol-5-yl)-5-aryl-1,2,4-oxadiazole derivatives as potential cytotoxic and antimicrobial agents

Globally cancer is the second leading cause of death;a drug that can cure cancer with the utmost negligible side effects is still a distant goal. Due to increasing antibiotic resistance, microbial infection remains a grave global health security threat. The ongoing coronavirus pandemic increased the risk of microbial and fungal infection. A new series of 3-(4-methyl-2-arylthiazol-5-yl)-5-aryl-1,2,4-oxadiazole (7a-t) have been synthesized. The structure of synthesized compounds was confirmed by the spectrometric analysis. The newly synthesized compounds were screened for cytotoxic activity against breast cell lines MCF-7 and MDA-MB-231. Against the MCF-7 cell line compounds 7f, 7 g and 7n showed excellent activity with GI50 0.6 muM to <100 nM concentration. Compound 7b showed good activity against MDA-MB-231 cell line with GI50 47 muM. The active derivatives 7b, 7e, 7f, 7 g and 7n were further evaluated for cytotoxicity against the epithelial cell line derived from the human embryonic kidney (HEK 293) and were found nontoxic. The thiazolyl-1,2,4-oxadiazole derivatives were also screened to evaluate theirs in vitro antimicrobial potential against Escherichia coli (NCIM 2574), Proteus mirabilis (NCIM 2388), Bacillus subtilis (NCIM 2063), Staphylococcus albus (NCIM 2178), Candida albicans (NCIM 3100) and Aspergillus niger (ATCC 504). Amongst the 7a-t derivatives, six compounds 7a, 7d, 7f, 7n, 7o, 7r showed good antifungal activity against C. albicans and eight compounds 7c, 7d, 7 g, 7h, 7i, 7k, 7l and 7o showed good activity against A. niger. The potential cytotoxic and antifungal activity suggested that the thiazolyl-1,2,4-oxadiazole derivatives could assist in the development of lead compounds for the treatment of cancer and microbial infections.Copyright © 2022 The Authors

Molecular Docking and Dynamics of Phytochemicals From Chinese Herbs With SARS-CoV-2 RdRp

The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is causing coronavirus disease 2019 (COVID-19) pandemic. Ancient Chinese herbal formulas are effective for diseases caused by viral infection, and their effects on COVID-19 are currently being examined. To directly evaluate the role of Chinese herbs in inhibiting replication of SARS-CoV-2, we investigated how the phytochemicals from Chinese herbs interact with the viral RNA-dependent RNA polymerase (RdRP). Total 1025 compounds were screened, and then 181compounds were selected for molecular docking analysis. Four phytochemicals licorice glycoside E, diisooctyl phthalate, (-)-medicocarpin, and glycyroside showed good binding affinity with RdRp. The best complex licorice glycoside E/RdRp forms 3 hydrogen bonds, 4 hydrophobic interactions, 1 pair of Pi-cation/stacking, and 4 salt bridges. Furthermore, docking complexes licorice glycoside E/RdRp and diisooctyl phthalate/RdRp were optimized by molecular dynamics simulation to obtain the stable conformation. These studies indicate that they are promising as antivirals against SARS-CoV-2.Copyright © The Author(s) 2022.

Establishing a Disease-in-a-Dish Model to Study SARS-CoV-2 Infection During Prenatal Development.

Mother-to-fetus transmission of the SARS-CoV-2 virus via the placenta has been reported but cannot readily be studied in pregnant women. This protocol describes an in vitro method to investigate SARS-CoV-2 infection of human embryonic stem cells (hESCs), which are similar to epiblast cells in young postimplantation embryos. First, SARS-CoV-2 viral pseudoparticles, which contain the spike protein and a fluorescent reporter, are incorporated into a lentivirus backbone that is expanded in HEK 293T cells. Then, an infection assay based on hESCs is used with the viral pseudoparticles. An application of the infection assay in therapeutic drug screening is provided. This protocol allows infection of hESCs by SARS-CoV-2 pseudoparticles to be studied in vitro and can be used in conjunction with other assays to understand and potentially prevent infection. hESCs could also be differentiated to study infection in the three germ layers and their fetal cell derivatives. This disease-in-a-dish model could be readily applied to other hESC lines, and to other viral infections, that affect human prenatal development. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Preparing HEK 293T cells for lentiviral vector transfection Support Protocol 1: Visual inspection of transfected HEK 293T cells Basic Protocol 2: Generating viral pseudoparticles Support Protocol 2: Determining viral titer with HEK 293T-ACE2 cells Basic Protocol 3: Plating hESCs for the infection assay Support Protocol 3: Evaluating transduction efficiency.

Jing Si Herbal Drink as a prospective adjunctive therapy for COVID-19 treatment: Molecular evidence and mechanisms

Background: SARS-CoV-2 has led to a sharp increase in the number of hospitalizations and deaths from pneumonia and multiorgan disease worldwide;therefore, SARS-CoV-2 has become a global health problem. Supportive therapies remain the mainstay treatments against COVID-19, such as oxygen inhalation, antiviral drugs, and antibiotics. Traditional Chinese medicine (TCM) has been shown clinically to relieve the symptoms of COVID-19 infection, and TCMs can affect the pathogenesis of SARS-CoV-2 infection in vitro. Jing Si Herbal Drink (JSHD), an eight herb formula jointly developed by Tzu Chi University and Tzu Chi Hospital, has shown potential as an adjuvant treatment for COVID-19 infection. A randomized controlled trial (RCT) of JSHD as an adjuvant treatment in patients with COVID-19 infection is underway Objectives: This article aims to explore the efficacy of the herbs in JSHD against COVID-19 infection from a mechanistic standpoint and provide a reference for the rational utilization of JSHD in the treatment of COVID-19. Method(s): We compiled evidence of the herbs in JSHD to treat COVID-19 in vivo and in vitro. Result(s): We described the efficacy and mechanism of action of the active ingredients in JSHD to treat COVID-19 based on experimental evidence. JSHD includes 5 antiviral herbs, 7 antioxidant herbs, and 7 anti-inflammatory herbs. In addition, 2 herbs inhibit the overactive immune system, 1 herb reduces cell apoptosis, and 1 herb possesses antithrombotic ability. Conclusion(s): Although experimental data have confirmed that the ingredients in JSHD are effective against COVID-19, more rigorously designed studies are required to confirm the efficacy and safety of JSHD as a COVID-19 treatment.Copyright © 2021

Screening of Natural Antivirals Against the COVID-19 Pandemic-A Compilation of Updates

Coronavirus disease 2019 (COVID-19), named by WHO, is a real public health disaster of the third millennium. This highly contagious viral disease has infected the world population and is now a global pandemic. This acute respiratory distress syndrome (ARDS) has severe complica-tions like pneumonitis, respiratory failure, shock, multiorgan failure, and death. Well-defined FDA-approved synthetic is not yet available. Case management strategies like lockdown, use of masks and sanitizers, social distancing, and repurposing of antiviral drugs were initially undertaken to cope with this pandemic. Different broad-spectrum antiviral drugs are being repurposed as one of the treatment modalities. The global vaccination programme with the newly launched COVID-19 vac-cines, Covishield, covaxin, sputnik V, etc., is an ongoing process. Simultaneously, significant research is being carried out in search of natural antivirals and evaluating the potency of food bioac-tives to aid naturistic protection against the coronavirus. This mini-review has compiled the latest updates on the screening and evidence-based mechanistic evaluation of phytochemicals and food bioactives as non-pharmacological adjuvant aid in COVID pandemics.Copyright © 2023 Bentham Science Publishers.

Pharmacokinetic evaluation of drug-drug interactions in the treatment of COVID-19.

Objective: The COVID-19 pandemic, which started in Wuhan, China and affected the whole world, still represents a unique global challenge with its contagiousness and lethality. The symptoms of COVID-19 patients may differ depending on the severity of the disease. According to the report published by the Ministry of Health Coronavirus Research Advisory Board on the diagnosis, treatment and control of COVID-19, drug combination therapy (hydroxychloroquine, lopinavir / ritonavir and favipiravir) is recommended by health authorities. Drug-drug interaction is a possible situation as a result of simultaneous use of these drugs, which are metabolized by cytochrome P 450 enzymes (CYP), which are mostly found in the liver, with some other drugs. In this review, we aimed to show the pharmacokinetic drug-drug interactions of the drugs used in the treatment of COVID-19, especially by indicating the metabolism pathways. Result and Discussion: The COVID-19 pandemic adversely affects social life, economic and financial markets worldwide. Appropriate treatment protocols are of great importance but taking drug-drug interactions into account in treatment practices prevents unwanted results in patient treatment.Copyright © 2021 University of Ankara. All rights reserved.

Pharmacokinetic evaluation of drug-drug interactions in the treatment of COVID-19.

Objective: The COVID-19 pandemic, which started in Wuhan, China and affected the whole world, still represents a unique global challenge with its contagiousness and lethality. The symptoms of COVID-19 patients may differ depending on the severity of the disease. According to the report published by the Ministry of Health Coronavirus Research Advisory Board on the diagnosis, treatment and control of COVID-19, drug combination therapy (hydroxychloroquine, lopinavir / ritonavir and favipiravir) is recommended by health authorities. Drug-drug interaction is a possible situation as a result of simultaneous use of these drugs, which are metabolized by cytochrome P 450 enzymes (CYP), which are mostly found in the liver, with some other drugs. In this review, we aimed to show the pharmacokinetic drug-drug interactions of the drugs used in the treatment of COVID-19, especially by indicating the metabolism pathways. Result and Discussion: The COVID-19 pandemic adversely affects social life, economic and financial markets worldwide. Appropriate treatment protocols are of great importance but taking drug-drug interactions into account in treatment practices prevents unwanted results in patient treatment.Copyright © 2021 University of Ankara. All rights reserved.

Investigating novel thiazolyl-indazole derivatives as scaffolds for SARS-CoV-2 MPro inhibitors

COVID-19 is a global pandemic caused by infection with the SARS-CoV-2 virus. Remdesivir, a SARS-CoV-2 RNA polymerase inhibitor, is the only drug to have received widespread approval for treatment of COVID-19. The SARS-CoV-2 main protease enzyme (MPro), essential for viral replication and transcription, remains an active target in the search for new treatments. In this study, the ability of novel thiazolyl-indazole derivatives to inhibit MPro is evaluated. These compounds were synthesized via the heterocyclization of phenacyl bromide with (R)-carvone, (R)-pulegone and (R)-menthone thiosemicarbazones. The binding affinity and binding interactions of each compound were evaluated through Schrodinger Glide docking, AMBER molecular dynamics simulations, and MM-GBSA free energy estimation, and these results were compared with similar calculations of MPro binding various 5-mer substrates (VKLQA, VKLQS, VKLQG) and a previously identified MPro tight-binder X77. From these simulations, we can see that binding is driven by residue specific interactions such as pi-stacking with His41, and S/pi interactions with Met49 and Met165. The compounds were also experimentally evaluated in a MPro biochemical assay and the most potent compound containing a phenylthiazole moiety inhibited protease activity with an IC50 of 92.9 muM. This suggests that the phenylthiazole scaffold is a promising candidate for the development of future MPro inhibitors.Copyright © 2022 The Authors

Potential clinical drugs as covalent inhibitors of the priming proteases of the spike protein of SARS-CoV-2.

In less than eight months, the COVID-19 (coronavirus disease 2019) caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus has resulted in over 20,000,000 confirmed cases and over 700,000 deaths around the world. With the increasing worldwide spreading of this disease, the lack of effective drugs against SARS-CoV-2 infection makes the situation even more dangerous and unpredictable. Although many forces are speeding up to develop prevention and treatment therapeutics, it is unlikely that any de novo drugs will be available in months. Drug repurposing holds the promise to significantly save the time for drug development, since it could use existing clinic drugs to treat new diseases. Based on the "steric-clashes alleviating receptor (SCAR)" strategy developed in our lab recently, we screened the library of clinic and investigational drugs, and identified nine drugs that might be repurposed as covalent inhibitors of the priming proteases (cathepsin B, cathepsin L, and TMPRSS2) of the spike protein of SARS-CoV-2. Among these hits, five are known covalent inhibitors, and one is an anti-virus drug. Therefore, we hope our work would provide rational and timely help for developing anti-SARS-CoV-2 drugs.

Evaluation of In Vitro and In Vivo Antiviral Activities of Vitamin D for SARS-CoV-2 and Variants.

The COVID-19 pandemic has brought about unprecedented medical and healthcare challenges worldwide. With the continual emergence and spread of new COVID-19 variants, four drug compound libraries were interrogated for their antiviral activities against SARS-CoV-2. Here, we show that the drug screen has resulted in 121 promising anti-SARS-CoV-2 compounds, of which seven were further shortlisted for hit validation: citicoline, pravastatin sodium, tenofovir alafenamide, imatinib mesylate, calcitriol, dexlansoprazole, and prochlorperazine dimaleate. In particular, the active form of vitamin D, calcitriol, exhibits strong potency against SARS-CoV-2 on cell-based assays and is shown to work by modulating the vitamin D receptor pathway to increase antimicrobial peptide cathelicidin expression. However, the weight, survival rate, physiological conditions, histological scoring, and virus titre between SARS-CoV-2 infected K18-hACE2 mice pre-treated or post-treated with calcitriol were negligible, indicating that the differential effects of calcitriol may be due to differences in vitamin D metabolism in mice and warrants future investigation using other animal models.

The North American opioid epidemic: opportunities and challenges for clinical laboratories.

Since 1999, the opioid epidemic in North America has resulted in over 1 million deaths, and it continues to escalate despite numerous efforts in various arenas to combat the upward trend. Clinical laboratories provide drug testing to support practices such as emergency medicine, substance use disorder treatment, and pain management; increasingly, these laboratories are collaborating in novel partnerships including drug-checking services (DCS) and multidisciplinary treatment teams. This review examines drug testing related to management of licit and illicit opioid use, new technologies and test strategies employed by clinical laboratories, barriers hindering laboratory response to the opioid epidemic, and areas for improvement and standardization within drug testing. Literature search terms included combinations of "opioid," "opiate," "fentanyl," "laboratory," "epidemic," "crisis," "mass spectrometry," "immunoassay," "drug screen," "drug test," "guidelines," plus review of PubMed "similar articles" and references within publications. While immunoassay (IA) and point-of-care (POC) test options for synthetic opioids are increasingly available, mass spectrometry (MS) platforms offer the greatest flexibility and sensitivity for detecting novel, potent opioids. Previously reserved as a second-tier application in most drug test algorithms, MS assays are gaining a larger role in initial screening for specific patients and DCS. However, there are substantial differences among laboratories in terms of updating test menus, algorithms, and technologies to meet changing clinical needs. While some clinical laboratories lack the resources and expertise to implement MS, many are also slow to adopt available IA and POC tests for newer opioids such as fentanyl. MS-based testing also presents challenges, including gaps in available guidance for assay validation and ongoing performance assessment that contribute to a dramatic lack of standardization among laboratories. We identify opportunities for improvement in laboratory operations, reporting, and interpretation of drug test results, including laboratorian and provider education and laboratory-focused guidelines. We also highlight the need for collaboration with providers, assay and instrument manufacturers, and national organizations to increase the effectiveness of clinical laboratory and provider efforts in preventing morbidity and mortality associated with opioid use and misuse.

Building Blood Vessel Chips with Enhanced Physiological Relevance

Blood vessel chips are bioengineered microdevices, consisting of biomaterials, human cells, and microstructures, which recapitulate essential vascular structure and physiology and allow a well-controlled microenvironment and spatial-temporal readouts. Blood vessel chips afford promising opportunities to understand molecular and cellular mechanisms underlying a range of vascular diseases. The physiological relevance is key to these blood vessel chips that rely on bioinspired strategies and bioengineering approaches to translate vascular physiology into artificial units. Here, several critical aspects of vascular physiology are discussed, including morphology, material composition, mechanical properties, flow dynamics, and mass transport, which provide essential guidelines and a valuable source of bioinspiration for the rational design of blood vessel chips. The state-of-art blood vessel chips are also reviewed that exhibit important physiological features of the vessel and reveal crucial insights into the biological processes and disease pathogenesis, including rare diseases, with notable implications for drug screening and clinical trials. It is envisioned that the advances in biomaterials, biofabrication, and stem cells improve the physiological relevance of blood vessel chips, which, along with the close collaborations between clinicians and bioengineers, enable their widespread utility. © 2023 Wiley-VCH GmbH.

Induced pluripotent stem cells: Generation methods and a new perspective in COVID-19 research.

Induced pluripotent stem cells (iPSCs) exhibit an unlimited ability to self-renew and produce various differentiated cell types, thereby creating high hopes for both scientists and patients as a great tool for basic research as well as for regenerative medicine purposes. The availability and safety of iPSCs for therapeutic purposes require safe and highly efficient methods for production of these cells. Different methods have been used to produce iPSCs, each of which has advantages and disadvantages. Studying these methods would be very helpful in developing an easy, safe, and efficient method for the generation of iPSCs. Since iPSCs can be generated from somatic cells, they can be considered as valuable cellular resources available for important research needs and various therapeutic purposes. Coronavirus disease 2019 (COVID-19) is a disease that has endangered numerous human lives worldwide and currently has no definitive cure. Therefore, researchers have been rigorously studying and examining all aspects of COVID-19 and potential treatment modalities and various drugs in order to enable the treatment, control, and prevention of COVID-19. iPSCs have become one of the most attractive and promising tools in this field by providing the ability to study COVID-19 and the effectiveness of drugs on this disease outside the human body. In this study, we discuss the different methods of generation of iPSCs as well as their respective advantages and disadvantages. We also present recent applications of iPSCs in the study and treatment of COVID-19.

Predicting Compound-Protein Interaction by Deepening the Systemic Background via Molecular Network Feature Embedding

Identifying compound-protein interactions (CPI) is crucial for drug screening, drug repurposing, and combination therapy studies. The performance of CPI prediction depends heavily on the features extracted from compounds and target proteins. The existing prediction methods use different feature combinations, but both molecular-based and network-based models have the problem of incomplete feature representations. Therefore, completely integrating the relevant features of CPI would be an effective way to solve the existing problem. This study proposed a novel model named MCPI, which integrated the PPI (protein-protein interaction) network, CCI (compound-compound interaction) network, and structure features of CPI to improve prediction performance. We compared our model with other existing methods for predicting CPI on public datasets. The experimental results showed that MCPI outperformed the peer methods. In addition, in response to the SARS-CoV-2 pandemic, we applied the model to search for potential inhibitors among FDA-approved drugs and validated the prediction results through the literature. This work may also provide potential guidance for drug development. © 2022 IEEE.