Potential herb‒drug interactions between anti-COVID-19 drugs and traditional Chinese medicine.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. Effective treatments against COVID-19 remain urgently in need although vaccination significantly reduces the incidence, hospitalization, and mortality. At present, antiviral drugs including Nirmatrelvir/Ritonavir (PaxlovidTM), Remdesivir, and Molnupiravir have been authorized to treat COVID-19 and become more globally available. On the other hand, traditional Chinese medicine (TCM) has been used for the treatment of epidemic diseases for a long history. Currently, various TCM formulae against COVID-19 such as Qingfei Paidu decoction, Xuanfei Baidu granule, Huashi Baidu granule, Jinhua Qinggan granule, Lianhua Qingwen capsule, and Xuebijing injection have been widely used in clinical practice in China, which may cause potential herb-drug interactions (HDIs) in patients under treatment with antiviral drugs and affect the efficacy and safety of medicines. However, information on potential HDIs between the above anti-COVID-19 drugs and TCM formulae is lacking, and thus this work seeks to summarize and highlight potential HDIs between antiviral drugs and TCM formulae against COVID-19, and especially pharmacokinetic HDIs mediated by metabolizing enzymes and/or transporters. These well-characterized HDIs could provide useful information on clinical concomitant medicine use to maximize clinical outcomes and minimize adverse and toxic effects.

Molecular Factors and Pathways of Hepatotoxicity Associated with HIV/SARS-CoV-2 Protease Inhibitors.

Antiviral protease inhibitors are peptidomimetic molecules that block the active catalytic center of viral proteases and, thereby, prevent the cleavage of viral polyprotein precursors into maturation. They continue to be a key class of antiviral drugs that can be used either as boosters for other classes of antivirals or as major components of current regimens in therapies for the treatment of infections with human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, sustained/lifelong treatment with the drugs or drugs combined with other substance(s) often leads to severe hepatic side effects such as lipid abnormalities, insulin resistance, and hepatotoxicity. The underlying pathogenic mechanisms are not fully known and are under continuous investigation. This review focuses on the general as well as specific molecular mechanisms of the protease inhibitor-induced hepatotoxicity involving transporter proteins, apolipoprotein B, cytochrome P450 isozymes, insulin-receptor substrate 1, Akt/PKB signaling, lipogenic factors, UDP-glucuronosyltransferase, pregnane X receptor, hepatocyte nuclear factor 4α, reactive oxygen species, inflammatory cytokines, off-target proteases, and small GTPase Rab proteins related to ER-Golgi trafficking, organelle stress, and liver injury. Potential pharmaceutical/therapeutic solutions to antiviral drug-induced hepatic side effects are also discussed.

Linear versus cubic regression models for analyzing generalized reverse degree based topological indices of certain latest corona treatment drug molecules

The major challenges encountered by medical researchers in developing new drugs are time consumption, increased cost, establishing a safety profile for the drugs, poor solubility, and inadequate experimental data. In its theoretical aspects, chemical graph theory plays a vital role in drug design and development by analyzing the structural parameters of molecules. Topological indices aim at the mathematical representation of a molecular structure, which is used to analyze the effectiveness of drugs and enhance the drug development process. In this study, we consider certain recently used drugs such as dexamethasone, molnupiravir, nirmatrelvir, ivermectin, ribavirin, baricitinib, favipiravir, duvelisib, L‐ascorbic acid, sofosbuvir, remdesivir, and pioglitazone for omicron, delta and other variants of coronaviruses. For these drug molecules, we propose a generalized form of reverse degree parameters and compute their associated topological indices with limiting behaviors. We undertake QSPR study on the potential of generalized reverse‐degree indices using linear and cubic regression models. [ FROM AUTHOR] Copyright of International Journal of Quantum Chemistry is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Drug-Induced Acute Pancreatitis in Hospitalized COVID-19 Patients.

Coronavirus disease-19 (COVID-19), caused by SARS-CoV-2, is a systemic disease that affects not only the respiratory system, but also other systems, including gastrointestinal. A great number of different drugs have been used on hospitalized patients for the management of COVID-19, and acute pancreatitis (AP) has been reported as a complication or side effect of these drugs. The development of drug-induced acute pancreatitis (DIAP) follows a complex of pathophysiological mechanisms, and particular risk factors play a key role. Diagnosis of DIAP depends on specific criteria, and based on these, a drug may be characterized as having a definite, probable or possible connection with AP. The aim of this review is to present the medications that are used for COVID-19 management and are associated with AP in hospitalized patients. The list of these drugs mainly includes corticosteroids, glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), antiviral agents, antibiotics, monoclonal antibodies, estrogens and anesthetic agents. Moreover, the prevention of the development of DIAP is vital, especially for critically ill patients who may receive multiple drugs. DIAP management is mainly non-invasive and the first step concerns the exception of the suspicious drug from patients therapy.

Repurposing of known drugs for COVID-19 using molecular docking and simulation analysis

We selected fifty one drugs already known for their potential disease treatment roles in various studies and subjected to docking and molecular docking simulation (MDS) analyses. Five of them showed promising features that are discussed and suggested as potential candidates for repurposing for COVID-19. These top five compounds were boswellic acid, pimecrolimus, GYY-4137, BMS-345541 and triamcinolone hexacetonide that interacted with the chosen receptors 1R42, 4G3D, 6VW1, 6VXX and 7MEQ, respectively with binding energies of -9.2 kcal/mol, -9.1 kcal/mol, -10.3 kcal/mol, -10.1 kcal/mol and -8.7 kcal/mol, respectively. The MDS studies for the top 5 best complexes revealed binding features for the chosen receptor, human NF-kappa B transcription factor as an important drug target in COVID-19-based drug development strategies.

Antiviral agents for COVID-19.

In December 2019, the endemic of COVID-19 broke out in Wuhan, China. The disease is highly contagious and quickly spreads at home and abroad, causing great concern. However, there are no definite effective antiviral drugs in clinical use. Given the urgency of the COVID-19 outbreak, based on the diagnosis and treatment recommendation and relavant researches, this article describes the optional antiviral drugs such as remdesivir, oseltamivir, arbidol, lopinavir/ritonavir, ribavirin, and interferon-alpha to provide a reference for treatment of COVID-19.Copyright © 2020 by the Chinese Medical Association.

Revealing Potential Binding Affinity of FDA Approved Therapeutics Targeting Main Protease (3CLpro) in Impairing Novel Coronavirus (SARS-CoV-2) Replication that Causes COVID-19

Background: Spread of COVID-19 attains a crucial transition in reveling its pandemic across the boundaries. In combating the infection caused by SARS-CoV-2, there is a spectrum of ideal strategies that have been adopted globally, of which repurposing of approved drugs considerably having high clinical relevance. 3-chymotrypsin-like protease (3CL pro) is considered to be the potential target for the researchers as it is highly essential for cleavage of polyprotein to get 16 nonstructural proteins (called nsp1-nsp16). These proteins are highly essential for viral replication and hence become a primary target for enzyme inhibitors. 3CL pro, having a structural projectile helical chain with biologically active site involved in processing viral polyproteins that are evolved from RNA genome translation. Objective(s): The major objective of the present investigation is to evaluate the enzyme inhibition potential of FDA approved therapeutic leads in targeting 3CLpro that medicates the viral replication. Method(s): Docking calculations were carried out for an array of FDA approved molecules which leads to a notable few molecules such as Emtricitabine, Oseltamivir, Ganciclovir, Chloroquine, Baricitinib, Favipiravir, Lopinavir, Ritonavir, Remdesivir, Ribavirin, Tenofovir, Umifenovir, Carbapenam, Ertap-enem and Imipenam which have both specificity and selectivity in terms of binding efficiency against 3CL proenzyme. Result(s): A combinatorial evaluation employing in-silico screening shows a major lead for remdesivir which possesses a substantial affinity to 3CL pro binding on core amino acid residues, such as Leu 27, His 41, Gly 143, Cys 145, His 164, Met 165, Glu 166, Pro 168 and His 172 which share the biological significance in mediating enzymatic action. Results of docking simulation by Autodock over a host of FDA approved molecules show high degree of selectivity and specificity in the increasing order of binding capacity;Remdesivir> Ertapenem> Imipenam> Tenofovir> Umifenovir> Chloroquine> Lopinavir> Ritonavir> Emtricitabine> Ganciclovir> Baricitinib> Ribavirin>Oseltamivir>Favipiravir> Carbapenam. Conclusion(s): Till date, there is no known cure attained for treating COVID-19 infection. In conclusion, lead molecules from already approved sources provoke promising potential which grabs the attention of the clinicians in availing potential therapeutic candidate as a drug of choice in the clinical management of COVID-19 time-dependently.Copyright © 2020 Bentham Science Publishers.

Review and expert evaluation of the materials of the European meeting on hypersensitivity to drugs (DHM 2022)

The review article discusses the current data on the mechanisms of hypersensitivity drugs reactions (HDRs). The relevance of the problem is associated with a significant prevalence of adverse drug reactions, in the structure of which immune allergic reactions occupy a significant proportion. Adverse drug reactions, according to the literature, occur in 10-20% of hospitalized patients and about 25% of outpatients. A serious problem of HDRs is their overdiagnosis, which affects the results of individual treatment and can have serious consequences in case of misdiagnosis, because it causes appropriate restrictions in the use of necessary drugs. Purpose - to analyze current views and recommendations on the problem of drug allergy;to highlight the issues of the 2022 meeting, which highlighted the problems of drug hypersensitivity. In particular, to show the relationship between viral infections and severe skin reactions, such as skin lesion syndrome with eosinophilia and systemic disorders. The article reviews and proposes algorithms that can be used to prevent the development of complications caused by HDRs. The materials of the article are based on the results of the European Meeting organized by the European Association of Allergists and Immunologists in 2022 in Verona, Italy. In the conclusions it is noted that despite the interest of the health care system and the large number of studies and publications on the problem of drug allergy, today there is an urgent need for accurate diagnostic approaches that will ensure the correct identification of the suspected drug by a combination of necessary tests and determine the cause for the possibility of prescribing appropriate treatment. The new mechanisms, phenotypes and endotypes of HDRs to drug responses discussed in the review are the future keys to preventing further exposure to harmful drugs. Preliminary pharmacogenomic screening (identification of specific human leukocyte antigen genotypes associated with severe skin adverse reactions) for patients of certain groups before prescribing high-risk drugs may become the future for Ukraine. © 2022 Group of Companies Med Expert, LLC. All rights reserved.

How to face COVID-19: proposed treatments based on remdesivir and hydroxychloroquine in the presence of zinc sulfate. Docking/DFT/POM structural analysis.

Remdesivir and hydroxychloroquine derivatives form two important classes of heterocyclic compounds. They are known for their anti-malarial biological activity. This research aims to analyze the physicochemical properties of remdesivir and hydroxychloroquine compounds by the computational approach. DFT, docking, and POM analyses also identify antiviral pharmacophore sites of both compounds. The antiviral activity of hydroxychloroquine compound's in the presence of zinc sulfate and azithromycin is evaluated through its capacity to coordinate transition metals (M = Cu, Ni, Zn, Co, Ru, Pt). The obtained bioinformatic results showed the potent antiviral/antibacterial activity of the prepared mixture (Hydroxychloroquine/Azithromycin/Zinc sulfate) for all the opportunistic Gram-positive, Gram-negative in the presence of coronavirus compared with the complexes Polypyridine-Ruthenium-di-aquo. The postulated zinc(II) complex of hydroxychloroquine derivatives are indeed an effective antibacterial and antiviral agent against coronavirus and should be extended to other pathogens. The combination of a pharmacophore site with a redox [Metal(OH2)2] moiety is of crucial role to fight against viruses and bacteria strains. [Formula: see text]Communicated by Ramaswamy H. Sarma.

COVID-19 Infection: A Review of Summarized Clinical Trials Study for the Treatment

Background: Coronavirus Disease 2019 (COVID-19) is a widely infectious and pathogenic viral infection. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was reported in Wu-han, China, and spread throughout the world. Coronavirus is indeed an enveloped RNA virus of the ge-nus Betacoronavirus, which is transmitted to birds, humans as well as other mammals. The fastest human to human transition has been generally established. On July 19, 2020, the WHO has reported total confirmed cases: 1,40, 43,176, total confirmed new cases: 1,66,735, total deaths: 5,97,583, and total new deaths: 4,496 globally. Material(s) and Method(s): In this review, the Clinical trial database is analyzed and systematically summarized drugs which are in the recruiting phase and the completion phase of the clinical trial. Result(s): Total 383 clinical trials are listed, involving more than 350 medicines such as Deferoxamine, Favipiravir, DAS181, Tocilizumab Injection, Sarilumab, Placebo, Sildenafil citrate tablets, Sargramo-stim, Lopinavir/ritonavir, Remdesivir, Bevacizumab, Tetrandrine, Fingolimod, Methylprednisolone, Plaquenil, Tocilizumab, Hydroxychloroquine, Abidol hydrochloride, Bevacizumab Injection, Methyl-prednisolone, Amoxicillin-clavulanate, Moxifloxacin, Sarilumab, Darunavir, Cobicistat, etc. Conclusion(s): There is no commercially authorized antiviral treatment or vaccine suitable for use against COVID-19. However, clinical trials represent an effective approach because they facilitate the development of new types of pharmaceutical drugs.Copyright © 2021 Bentham Science Publishers.

Assessment of GO-Based Protein Interaction Affinities in the Large-Scale Human-Coronavirus Family Interactome.

SARS-CoV-2 is a novel coronavirus that replicates itself via interacting with the host proteins. As a result, identifying virus and host protein-protein interactions could help researchers better understand the virus disease transmission behavior and identify possible COVID-19 drugs. The International Committee on Virus Taxonomy has determined that nCoV is genetically 89% compared to the SARS-CoV epidemic in 2003. This paper focuses on assessing the host-pathogen protein interaction affinity of the coronavirus family, having 44 different variants. In light of these considerations, a GO-semantic scoring function is provided based on Gene Ontology (GO) graphs for determining the binding affinity of any two proteins at the organism level. Based on the availability of the GO annotation of the proteins, 11 viral variants, viz., SARS-CoV-2, SARS, MERS, Bat coronavirus HKU3, Bat coronavirus Rp3/2004, Bat coronavirus HKU5, Murine coronavirus, Bovine coronavirus, Rat coronavirus, Bat coronavirus HKU4, Bat coronavirus 133/2005, are considered from 44 viral variants. The fuzzy scoring function of the entire host-pathogen network has been processed with ~180 million potential interactions generated from 19,281 host proteins and around 242 viral proteins. ~4.5 million potential level one host-pathogen interactions are computed based on the estimated interaction affinity threshold. The resulting host-pathogen interactome is also validated with state-of-the-art experimental networks. The study has also been extended further toward the drug-repurposing study by analyzing the FDA-listed COVID drugs.

COVID-19 and atrial fibrillation: Intercepting lines.

Almost 20% of COVID-19 patients have a history of atrial fibrillation (AF), but also a new-onset AF represents a frequent complication in COVID-19. Clinical evidence demonstrates that COVID-19, by promoting the evolution of a prothrombotic state, increases the susceptibility to arrhythmic events during the infective stages and presumably during post-recovery. AF itself is the most frequent form of arrhythmia and is associated with substantial morbidity and mortality. One of the molecular factors involved in COVID-19-related AF episodes is the angiotensin-converting enzyme (ACE) 2 availability. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 to enter and infect multiple cells. Atrial ACE2 internalization after binding to SARS-CoV-2 results in a raise of angiotensin (Ang) II, and in a suppression of cardioprotective Ang(1-7) formation, and thereby promoting cardiac hypertrophy, fibrosis and oxidative stress. Furthermore, several pharmacological agents used in COVID-19 patients may have a higher risk of inducing electrophysiological changes and cardiac dysfunction. Azithromycin, lopinavir/ritonavir, ibrutinib, and remdesivir, used in the treatment of COVID-19, may predispose to an increased risk of cardiac arrhythmia. In this review, putative mechanisms involved in COVID-19-related AF episodes and the cardiovascular safety profile of drugs used for the treatment of COVID-19 are summarized.

Drug-Induced Liver Injury in Hospitalized Patients during SARS-CoV-2 Infection.

In the last few years, the world has had to face the SARS-CoV-2 infection and its multiple effects. Even though COVID-19 was first considered to be a respiratory disease, it has an extended clinical spectrum with symptoms occurring in many tissues, and it is now identified as a systematic disease. Therefore, various drugs are used during the therapy of hospitalized COVID-19 patients. Studies have shown that many of these drugs could have adverse side-effects, including drug-induced liver injury-also known as DILI-which is the focus of our review. Despite the consistent findings, the pathophysiological mechanism behind DILI in COVID-19 disease is still complex, and there are a few risk factors related to it. However, when it comes to the diagnosis, there are specific algorithms (including the RUCAM algorithm) and biomarkers that can assist in identifying DILI and which we will analyze in our review. As indicated by the title, a variety of drugs are associated with this COVID-19-related complication, including systemic corticosteroids, drugs used for the therapy of uncontrolled cytokine storm, as well as antiviral, anti-inflammatory, and anticoagulant drugs. Bearing in mind that hepatotoxicity is very likely to occur during COVID-19, especially in patients treated with multiple medications, we will also refer to the use of other drugs used for DILI therapy in an effort to control and prevent a severe and long-term outcome.

Adverse effect signature extraction and prediction for drugs treating COVID-19.

Given the considerable cost of drug discovery, drug repurposing is becoming attractive as it can effectively shorten the development timeline and reduce the development cost. However, most existing drug-repurposing methods omitted the heterogeneous health conditions of different COVID-19 patients. In this study, we evaluated the adverse effect (AE) profiles of 106 COVID-19 drugs. We extracted four AE signatures to characterize the AE distribution of 106 COVID-19 drugs by non-negative matrix factorization (NMF). By integrating the information from four distinct databases (AE, bioassay, chemical structure, and gene expression information), we predicted the AE profiles of 91 drugs with inadequate AE feedback. For each of the drug clusters, discriminant genes accounting for mechanisms of different AE signatures were identified by sparse linear discriminant analysis. Our findings can be divided into three parts. First, drugs abundant with AE-signature 1 (for example, remdesivir) should be taken with caution for patients with poor liver, renal, or cardiac functions, where the functional genes accumulate in the RHO GTPases Activate NADPH Oxidases pathway. Second, drugs featuring AE-signature 2 (for example, hydroxychloroquine) are unsuitable for patients with vascular disorders, with relevant genes enriched in signal transduction pathways. Third, drugs characterized by AE signatures 3 and 4 have relatively mild AEs. Our study showed that NMF and network-based frameworks contribute to more precise drug recommendations.

Quantitative structure-properties relationship analysis of Eigen-value-based indices using COVID-19 drugs structure.

Topological indices are an important method for understanding the fundamental topology of chemical structures. Quantitative structure properties relationship (QSPR) is an analytical approach for breaking down a molecule into a sequence of numerical values that describe the chemical and physical characteristics of the molecule. In this article, we have developed the QSPR analysis between eigenvalue-based topological indices and physical properties of COVID-19 drugs to predict the significance level of eigenvalue based indices. We have to use MATLAB for the computation of indices and SPSS for analysis. We show that positive interia index, signless Laplacian Estrada index and Randic energy are the best predictors of molar reactivity, polar surface area and molecular weight, respectively.

QSPR Modeling of Status-Based Topological Indices with COVID-19 Drugs

The severe acute metabolic process syndrome coronavirus-2 (SARS-CoV-2) virus strain causes an unique Corona viral (COVID-19) disease. It was initially documented in the foreign country of China, and it has since spread around the world. Fever, cough, and runny nose are among the symptoms of this illness, which mostly affects the respiratory system. The peculiar thing is that there is no therapy or vaccine available for this sickness. Clinical trials for a corona virus vaccine are still ongoing, with the vaccine likely to be available by 2021. Until then, the only way to deal with or control the virus’s spread is to take preventative precautions. The numerical descriptors of a molecule structure obtained by the molecular graph are known as topological indices. These can be utilized in structure-property relationship (QSPR) and structure-activity relationship (QSAR) investigations to learn a lot about a molecule’s physicochemical and biological properties. Lopinavir, ritonavir, arbidol, thalidomide, chloroquine, hydroxy-chloroquine, theaflavin, and remdesivir are investigated in this research as crucial lights in COVID-19 treatment. For chemical graphs of these medications, some status distance-based topological indices are constructed. Furthermore, these topological indices are used in the QSPR models to estimate some of the medications’ physicochemical properties. The results of the QSPR experiments, which were acquired using the polynomial regression technique, can contribute in the development of new drugs for the treatment of COVID-19. [ FROM AUTHOR] Copyright of Polycyclic Aromatic Compounds is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

SARS-CoV-2 pharmaceutical drugs: a critical review on the environmental impacts, chemical characteristics, and behavior of advanced oxidation processes in water.

This review summarizes research data on the pharmaceutical drugs used to treat the novel SARS-CoV-2 virus, their characteristics, environmental impacts, and the advanced oxidation processes (AOP) applied to remove them. A literature survey was conducted using the electronic databases Science Direct, Scopus, Taylor & Francis, Google Scholar, PubMed, and Springer. This complete research includes and discusses relevant studies that involve the introduction, pharmaceutical drugs used in the SARS-CoV-2 pandemic: chemical characteristics and environmental impact, advanced oxidation process (AOP), future trends and discussion, and conclusions. The results show a full approach in the versatility of AOPs as a promising solution to minimize the environmental impact associated with these compounds by the fact that they offer different ways for hydroxyl radical production. Moreover, this article focuses on introducing the fundamentals of each AOP, the main parameters involved, and the concomitance with other sources and modifications over the years. Photocatalysis, sonochemical technologies, electro-oxidation, photolysis, Fenton reaction, ozone, and sulfate radical AOP have been used to mineralize SARS-CoV-2 pharmaceutical compounds, and the efficiencies are greater than 65%. According to the results, photocatalysis is the main technology currently applied to remove these pharmaceuticals. This process has garnered attention because solar energy can be directly utilized; however, low photocatalytic efficiencies and high costs in large-scale practical applications limit its use. Furthermore, pharmaceuticals in the environment are diverse and complex. Finally, the review also provides ideas for further research needs and major concerns.

Core shell stationary phase for a novel separation of some COVID-19 used drugs by UPLC-MS/MS Method: Study of grapefruit consumption impact on their pharmacokinetics in rats.

A sensitive and selective UPLC-MS/MS method was developed for the synchronized determination of four drugs used in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), namely, azithromycin, apixaban, dexamethasone, and favipiravir in rat plasma. using a Poroshell 120 EC-C18 column (50 mm × 4.6 mm, 2.7 m) with a high-resolution ESI tandem mass spectrometer detection with multiple reaction monitoring. We used an Agilent Poroshell column, which is characterized by a stationary phase based on non-porous core particles. With a remarkable improvement in the number of theoretical plates and low column backpressure. In addition, the developed method was employed in studying the potential food-drug interaction of grapefruit juice (GFJ) with the selected drugs which affects their pharmacokinetics in rats. The LC-MS/MS operated in positive and negative ionization mode using two internal standards: moxifloxacin and chlorthalidone, respectively. Liquid- liquid extraction of the cited drugs from rat plasma was accomplished using diethyl ether: dichloromethane (70:30, v/v). The analytes were separated using methanol: 0.1 % formic acid in water (95: 5, v/v) as a mobile phase in isocratic mode of elution pumped at a flow rate of 0.3 mL/min. A detailed validation of the bio-analytical method was performed in accordance with US-FDA and EMA guidelines. Concerning the in vivo pharmacokinetic study, the statistical significance between the results of the test groups receiving GFJ along with the cited drugs and the control group was assessed demonstrating that GFJ increased the plasma concentration of azithromycin, apixaban, and dexamethasone. Accordingly, this food-drug interaction requires cautious ingestion of GFJ in patients using (SARS-CoV-2) medications as it can produce negative effects in the safety of the drug therapy. A potential drug-drug interaction is also suggested between those medications requiring a suitable dose adjustment.

Repositioning Therapeutics for SARS-CoV-2: Virtual Screening of Plant-based Anti-HIV Compounds as Possible Inhibitors against COVID-19 Viral RdRp.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a global pandemic with a high mortality and morbidity rate worldwide. The COVID-19 vaccines that are currently in development or already approved are expected to provide at least some protection against the emerging variants of the virus, but the mutations may reduce the efficacy of the existing vaccines. Purified phytochemicals from medicinal plants provide a helpful framework for discovering new therapeutic leads as they have long been employed in traditional medicine to treat many disorders. OBJECTIVE: The objectives of the study are to exploit the anti-HIV bioactive compounds against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) through molecular docking studies and to evaluate the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of potential compounds. METHODS: Molecular docking was performed to study the interaction of ligands with the target sites of RdRp protein (PDB: 6M71) using AutoDock Vina. The ADMET properties of potential compounds were predicted using the pkCSM platform. RESULTS: A total of 151 phytochemicals derived from the medicinal plants with recognized antiviral activity and 18 anti-HIV drugs were virtually screened against COVID-19 viral RdRp to identify putative inhibitors that facilitate the development of potential anti-COVID-19 drug candidates. The computational studies identified 34 compounds and three drugs inhibiting viral RdRp with binding energies ranging from -10.2 to -8.5 kcal/mol. Among them, five compounds, namely Michellamine B, Quercetin 3-O-(2'',6''-digalloyl)-beta-Dgalactopyranoside, Corilagin, Hypericin, and 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose residues, bound efficiently with the binding site of RdRp. Besides, Lopinavir, Maraviroc, and Remdesivir drugs also inhibited SARS-CoV-2 polymerase. In addition, the ADMET properties of top potential compounds were also predicted in comparison to the drugs. CONCLUSION: The present study suggested that these potential drug candidates can be further subjected to in vitro and in vivo studies that may help develop effective anti-COVID-19 drugs.

In Silico Screening of Novel TMPRSS2 Inhibitors for Treatment of COVID-19.

COVID-19, a pandemic caused by the virus SARS-CoV-2, has spread globally, necessitating the search for antiviral compounds. Transmembrane protease serine 2 (TMPRSS2) is a cell surface protease that plays an essential role in SARS-CoV-2 infection. Therefore, researchers are searching for TMPRSS2 inhibitors that can be used for the treatment of COVID-19. As such, in this study, based on the crystal structure, we targeted the active site of TMPRSS2 for virtual screening of compounds in the FDA database. Then, we screened lumacaftor and ergotamine, which showed strong binding ability, using 100 ns molecular dynamics simulations to study the stability of the protein-ligand binding process, the flexibility of amino acid residues, and the formation of hydrogen bonds. Subsequently, we calculated the binding free energy of the protein-ligand complex by the MM-PBSA method. The results show that lumacaftor and ergotamine interact with residues around the TMPRSS2 active site, and reached equilibrium in the 100 ns molecular dynamics simulations. We think that lumacaftor and ergotamine, which we screened through in silico studies, can effectively inhibit the activity of TMPRSS2. Our findings provide a basis for subsequent in vitro experiments, having important implications for the development of effective anti-COVID-19 drugs.