Self-aggregation behaviour of novel thiosemicarbazone drug candidates with potential antiviral activity

A new π-conjugated copolymer containing tetrathiafulvalene vinylogue and pyrene repeat units was synthesized and exhibited reversible redox activity, while the self-aggregation behaviour in the solution phase was responsive to external stimuli such as solvent and pH value.

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Self-aggregation behaviour of cationic surfactant tetradecyltrimethylammonium bromide and bi-amphiphilic surface active ionic liquid 3-methyl-1-pentylimidazolium dodecylsulfate in aqueous solution

Journal of Molecular Liquids ◽

10.1016/j.molliq.2020.112803 ◽

2020 ◽

Vol 304 ◽

pp. 112803

Author(s):

Amalendu Pal ◽

Renu Punia

Keyword(s):

Aqueous Solution ◽

Ionic Liquid ◽

Cationic Surfactant ◽

Tetradecyltrimethylammonium Bromide ◽

Aggregation Behaviour ◽

Surface Active Ionic Liquid ◽

Surface Active ◽

Self Aggregation

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Elucidation on the Physicochemical Properties of Potential and Clinically Approved Antiviral Drugs: A Search for Effective Therapies against SARS-CoV-2 Infection

Journal of Pure and Applied Microbiology ◽

10.22207/jpam.14.spl1.41 ◽

2020 ◽

Vol 14 (suppl 1) ◽

pp. 1025-1034

Author(s):

Derick Erl P. Sumalapao

Keyword(s):

Antiviral Activity ◽

Physicochemical Properties ◽

Vaccine Development ◽

Heavy Atom ◽

Antiviral Drug ◽

Principal Component ◽

Antiviral Drugs ◽

Medical Emergency ◽

Drug Candidates ◽

Additional Information

COVID-19 has been confirmed in millions of individuals worldwide, rendering it a global medical emergency. In the absence of vaccines and the unavailability of effective drugs for the SARS-CoV-2 infection, vaccine development is being continuously explored and several antiviral compounds and immunotherapies are currently being investigated. Given the high similarity in genetic identity between SARS-CoV and SARS-CoV-2, the present investigation identified the interaction between the physicochemical properties and the antiviral activity of different potential and clinically approved antiviral drugs against SARS-CoV using hierarchically weighted principal component analysis. Representative drugs from the classes of neuraminidase inhibitors, reverse transcriptase inhibitors, protease inhibitors, nucleoside analogues, and other compounds with potential antiviral activity were examined. The pharmacologic classification and the biological activity of the different antiviral drugs were described using indices, namely, rotatable bond count, molecular weight, heavy atom count, and molecular complexity (92.32% contribution rate). The physicochemical properties and inhibitory action against SARS-CoV-2 of lopinavir, chloroquine, ivermectin, and ciclesonide validated the adequacy of the current computational approach. The findings of the present study provide additional information, although further investigation is warranted to identify potential targets and establish exact mechanisms, in the emergent search and design of antiviral drug candidates and their subsequent synthesis as effective therapies for COVID-19.

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Boceprevir, calpain inhibitors II and XII, and GC-376 have broad-spectrum antiviral activity against coronaviruses in cell culture

10.1101/2020.10.30.362335 ◽

2020 ◽

Author(s):

Yanmei Hu ◽

Chunlong Ma ◽

Tommy Szeto ◽

Brett Hurst ◽

Bart Tarbet ◽

...

Keyword(s):

Cell Culture ◽

Antiviral Activity ◽

Cathepsin L ◽

Antiviral Drug ◽

Antiviral Effect ◽

Neutralization Assay ◽

Drug Candidates ◽

Main Protease ◽

Human Coronaviruses ◽

Calpain Inhibitors

AbstractAs the COVID-19 pandemic continues to fold out, the morbidity and mortality are increasing daily. Effective treatment for SARS-CoV-2 is urgently needed. We recently discovered four SARS-CoV-2 main protease (Mpro) inhibitors including boceprevir, calpain inhibitors II and XII and GC-376 with potent antiviral activity against infectious SARS-CoV-2 in cell culture. Despite the weaker enzymatic inhibition of calpain inhibitors II and XII against Mpro compared to GC-376, calpain inhibitors II and XII had more potent cellular antiviral activity. This observation promoted us to hypothesize that the cellular antiviral activity of calpain inhibitors II and XII might also involve the inhibition of cathepsin L in addition to Mpro. To test this hypothesis, we tested calpain inhibitors II and XII in the SARS-CoV-2 pseudovirus neutralization assay in Vero E6 cells and found that both compounds significantly decreased pseudoviral particle entry into cells, indicating their role in inhibiting cathepsin L. The involvement of cathepsin L was further confirmed in the drug time-of-addition experiment. In addition, we found that these four compounds not only inhibit SARS-CoV-2, but also SARS-CoV, MERS-CoV, as well as human coronaviruses (CoVs) 229E, OC43, and NL63. The mechanism of action is through targeting the viral Mpro, which was supported by the thermal shift binding assay and enzymatic FRET assay. We further showed that these four compounds have additive antiviral effect when combined with remdesivir. Altogether, these results suggest that boceprevir, calpain inhibitors II and XII, and GC-376 are not only promising antiviral drug candidates against existing human coronaviruses, but also might work against future emerging CoVs.

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Drug repurposing against SARS-CoV-1, SARS-CoV-2 and MERS-CoV

Future Microbiology ◽

10.2217/fmb-2021-0019 ◽

2021 ◽

Author(s):

Sarah Aherfi ◽

Bruno Pradines ◽

Christian Devaux ◽

Stéphane Honore ◽

Philippe Colson ◽

...

Keyword(s):

Molecular Docking ◽

Antiviral Activity ◽

Oral Administration ◽

Low Cost ◽

Drug Repurposing ◽

Toxicity Profile ◽

In Silico Screening ◽

Drug Candidates ◽

Reduced Time

Since the beginning of the COVID-19 pandemic, large in silico screening studies and numerous in vitro studies have assessed the antiviral activity of various drugs on SARS-CoV-2. In the context of health emergency, drug repurposing represents the most relevant strategy because of the reduced time for approval by international medicines agencies, the low cost of development and the well-known toxicity profile of such drugs. Herein, we aim to review drugs with in vitro antiviral activity against SARS-CoV-2, combined with molecular docking data and results from preliminary clinical studies. Finally, when considering all these previous findings, as well as the possibility of oral administration, 11 molecules consisting of nelfinavir, favipiravir, azithromycin, clofoctol, clofazimine, ivermectin, nitazoxanide, amodiaquine, heparin, chloroquine and hydroxychloroquine, show an interesting antiviral activity that could be exploited as possible drug candidates for COVID-19 treatment.

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Antiviral Activity of CD437 Against Mumps Virus

Frontiers in Microbiology ◽

10.3389/fmicb.2021.751909 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fumihiro Kato ◽

Yuichiro Nakatsu ◽

Keiko Murano ◽

Aika Wakata ◽

Toru Kubota ◽

...

Keyword(s):

Antiviral Activity ◽

Fluorescent Protein ◽

Screening Method ◽

Antiviral Drug ◽

Mumps Virus ◽

Screening Methods ◽

Drug Candidates ◽

Late Step ◽

Key Factor ◽

Green Fluorescent

Many efforts have been dedicated to the discovery of antiviral drug candidates against the mumps virus (MuV); however, no specific drug has yet been approved. The development of efficient screening methods is a key factor for the discovery of antiviral candidates. In this study, we evaluated a screening method using an Aequorea coerulescens green fluorescent protein-expressing MuV infectious molecular clone. The application of this system to screen for active compounds against MuV replication revealed that CD437, a retinoid acid receptor agonist, has anti-MuV activity. The point of antiviral action was a late step(s) in the MuV life cycle. The replication of other paramyxoviruses was also inhibited by CD437. The induction of retinoic acid-inducible gene (RIG)-I expression is a reported mechanism for the antiviral activity of retinoids, but our results indicated that CD437 did not stimulate RIG-I expression. Indeed, we observed antiviral activity despite the absence of RIG-I, suggesting that CD437 antiviral activity does not require RIG-I induction.

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Pyrimidine biosynthesis inhibitors synergize with nucleoside analogs to block SARS-CoV-2 infection

10.1101/2021.06.24.449811 ◽

2021 ◽

Author(s):

David Schultz ◽

Robert Johnson ◽

Kasirajan Ayyanathan ◽

Jesse Miller ◽

Kanupriya Whig ◽

...

Keyword(s):

Antiviral Activity ◽

Viral Infections ◽

Nucleoside Analogs ◽

Pyrimidine Biosynthesis ◽

Live Virus ◽

Drug Candidates ◽

Biosynthesis Inhibitors ◽

Approved Drugs

The ongoing COVID-19 pandemic has highlighted the dearth of approved drugs to treat viral infections, with only ~90 FDA approved drugs against human viral pathogens. To identify drugs that can block SARS-CoV-2 replication, extensive drug screening to repurpose approved drugs is underway. Here, we screened ~18,000 drugs for antiviral activity using live virus infection in human respiratory cells. Dose-response studies validate 122 drugs with antiviral activity and selectivity against SARS-CoV-2. Amongst these drug candidates are 16 nucleoside analogs, the largest category of clinically used antivirals. This included the antiviral Remdesivir approved for use in COVID-19, and the nucleoside Molnupirivir, which is undergoing clinical trials. RNA viruses rely on a high supply of nucleoside triphosphates from the host to efficiently replicate, and we identified a panel of host nucleoside biosynthesis inhibitors as antiviral, and we found that combining pyrimidine biosynthesis inhibitors with antiviral nucleoside analogs synergistically inhibits SARS-CoV-2 infection in vitro and in vivo suggesting a clinical path forward.

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New Chalcone Derivatives as Effective Anti-SARS-CoV-2 Agents

10.21203/rs.3.rs-515050/v1 ◽

2021 ◽

Author(s):

Nizami Duran ◽

M. Fatih Polat ◽

Derya Anil Aktas ◽

M. Abdullah Alagoz ◽

Emrah Ay ◽

...

Keyword(s):

Antiviral Activity ◽

Antiviral Drug ◽

Rt Pcr ◽

Chalcone Derivatives ◽

Drug Candidates ◽

Angelica Keiskei ◽

Antiviral Activities ◽

Computational Analyses ◽

Dose Dependent ◽

Related Compounds

Abstract Flavonoids and related compounds, such as quercetin-based antiviral drug Gene-Eden-VIR/Novirin, inhibit the protease of severe acute respiratory syndrome coronavirus (SARS-CoV-2). The alkylated chalcones isolated from Angelica keiskei inhibit SARS-CoV proteases. Hydroxychloroquine and Favipiravir have been used in many countries since the beginning of the pandemic with the thought that they may have antiviral activity against SARS CoV-2. In this study, we aimed to compare the anti-SARS CoV-2 activities of both newly synthesized chalcone derivatives and these two drugs.The current study aimed to determine the potent antiviral activity of newly synthesized chalcone derivatives against SARS-CoV-2 by calculating the RT-PCR cycling threshold (Ct) values. Antiviral activities of the compounds varied due to being dose dependent. Compound 6, 7, 9 and 16 were highly effective against SARS-CoV-2 at concentrations of 1.60 µg/mL. Structure-based virtual screening was carried out against the most important druggable SARS-CoV-2 targets, viral RNA-dependent RNA polymerase (RdRp), to identify putative inhibitors that could facilitate the development of potential anti-COVID-19 drug candidates. Computational analyses identified eight compounds inhibiting each target, with binding affinity scores ranging from − 4,370 to -2,748 kcal/mol along with their toxicological, ADME, and drug-like properties.

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The self-aggregation behaviour of amphotericin B-loaded polyrotaxane-based triblock copolymers and their hemolytic evaluation

Soft Matter ◽

10.1039/b914664d ◽

2009 ◽

Vol 5 (23) ◽

pp. 4797 ◽

Cited By ~ 20

Author(s):

Xiaowen Zhang ◽

Fuyou Ke ◽

Jian Han ◽

Lin Ye ◽

Dehai Liang ◽

...

Keyword(s):

Amphotericin B ◽

Triblock Copolymers ◽

The Self ◽

Aggregation Behaviour ◽

Self Aggregation

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Drug Repurposing and Polypharmacology to Fight SARS-CoV-2 Through Inhibition of the Main Protease

Frontiers in Pharmacology ◽

10.3389/fphar.2021.636989 ◽

2021 ◽

Vol 12 ◽

Cited By ~ 1

Author(s):

Luca Pinzi ◽

Annachiara Tinivella ◽

Fabiana Caporuscio ◽

Giulio Rastelli

Keyword(s):

Clinical Trials ◽

Antiviral Activity ◽

Inhibitory Activity ◽

Therapeutic Indication ◽

Drug Repurposing ◽

Drug Candidates ◽

Main Protease ◽

The World ◽

Potential Inhibitors ◽

Late Stages

The outbreak of a new coronavirus (SARS-CoV-2), which is responsible for the COVID-19 disease and is spreading rapidly around the world, urgently requires effective therapeutic treatments. In this context, drug repurposing represents a valuable strategy, as it enables accelerating the identification of drug candidates with already known safety profiles, possibly aiding in the late stages of clinical evaluation. Moreover, therapeutic treatments based on drugs with beneficial multi-target activities (polypharmacology) may show an increased antiviral activity or help to counteract severe complications concurrently affecting COVID-19 patients. In this study, we present the results of a computational drug repurposing campaign that aimed at identifying potential inhibitors of the main protease (Mpro) of the SARS-CoV-2. The performedin silicoscreening allowed the identification of 22 candidates with putative SARS-CoV-2 Mproinhibitory activity. Interestingly, some of the identified compounds have recently entered clinical trials for COVID-19 treatment, albeit not being assayed for their SARS-CoV-2 antiviral activity. Some candidates present a polypharmacology profile that may be beneficial for COVID-19 treatment and, to the best of our knowledge, have never been considered in clinical trials. For each repurposed compound, its therapeutic relevance and potential beneficial polypharmacological effects that may arise due to its original therapeutic indication are thoroughly discussed.

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