Discovery of novel papain-like protease inhibitors for potential treatment of COVID-19

Hersi, Fatema; Sebastian, Anusha; Tarazi, Hamadeh; Srinivasulu, Vunnam; Mostafa, Ahmed; Allayeh, Abdou Kamal; Zeng, Cong; Hachim, Ibrahim Y.; Liu, Shan-Lu; Abu‐Yousef, Imad A.; Majdalawieh, Amin F.; Zaher, Dana M.; Omar, Hany A.; Al‐Tel, Taleb H.

doi:10.1016/j.ejmech.2023.115380

Cited by 12 publications

(3 citation statements)

References 72 publications

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“…This inhibitor possesses a structure of the type 99 (Scheme 10). [104] These findings demonstrate the power of utilizing nature-inspired architectures in a CtD strategy to generate a skeletally and stereochemically diverse compound collections leading to novel chemotypes. [70,101,[105][106][107]…”

Section: Ctd Using Indolo Monoterpenoids Nature-inspired Compoundsmentioning

confidence: 81%

Complexity‐to‐Diversity and Pseudo‐Natural Product Strategies as Powerful Platforms for Deciphering Next‐Generation Therapeutics

et al. 2023

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Stereochemical and skeletal complexity are particularly important vis‐à‐vis the cross‐talks between a small molecule and a complementary active site of a biological target. This intricate harmony is known to increase selectivity, reduce toxicity, and increase the success rate in clinical trials. Therefore, the development of novel strategies for establishing underrepresented chemical space that is rich in stereochemical and skeletal diversity is an important milestone in a drug discovery campaign. In this review, we discuss the evolution of interdisciplinary synthetic methodologies utilized in chemical biology and drug discovery that has revolutionized the discovery of first‐in‐class molecules over the last decade with an emphasis on complexity‐to‐diversity and pseudo‐natural product strategies as a remarkable toolbox for deciphering next‐generation therapeutics. We also report how these approaches dramatically revolutionized the discovery of novel chemical probes that target underrepresented biological space. We also highlight selected applications and discuss key opportunities offered by these tools and important synthetic strategies used for the construction of chemical spaces that are rich in skeletal and stereochemical diversity. We also provide insight on how the integration of these protocols has the promise of changing the drug discovery landscape.

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Section: Ctd Using Indolo Monoterpenoids Nature-inspired Compoundsmentioning

confidence: 81%

Complexity‐to‐Diversity and Pseudo‐Natural Product Strategies as Powerful Platforms for Deciphering Next‐Generation Therapeutics

et al. 2023

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“…To compute the antiviral efficiency percentage of any substance, we use the subsequent formula: antiviral efficiency = [(cell controls’ mean optical density minus virus controls)/(the test optical density minus virus controls)] × 100. Based on these data, the 50% CPE inhibitory dose (ID 50 ) was calculated [ 16 , 57 ].…”

Section: Methodsmentioning

confidence: 99%

“…Consequently, remdesivir is the main FDA-approved drug for treating severe COVID-19 symptoms within the classification of RdRp inhibitors. Consequently, remdesivir is the main FDA-approved drug for treating severe COVID-19 symptoms within the classification of RdRp inhibitors [ 16 ]. Furthermore, molnupiravir affects by starting the initiation of viral RNA alterations, which eventually prevents SARS-CoV-2 from replicating.…”

Section: Introductionmentioning

confidence: 99%

Discovery of Pyrano[2,3-c]pyrazole Derivatives as Novel Potential Human Coronavirus Inhibitors: Design, Synthesis, In Silico, In Vitro, and ADME Studies

Allayeh,

El-boghdady,

Said

et al. 2024

Pharmaceuticals

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The SARS-CoV-2 pandemic at the end of 2019 had major worldwide health and economic consequences. Until effective vaccination approaches were created, the healthcare sectors endured a shortage of operative treatments that might prevent the infection’s spread. As a result, academia and the pharmaceutical industry prioritized the development of SARS-CoV2 antiviral medication. Pyranopyrazoles have been shown to play a prominent function in pharmaceutical chemistry and drug sighting because of their significant bioactive properties. We provide herein a novel sequence of pyranopyrazoles and their annulated systems whose antiviral efficacy and cytotoxicity were explored versus human coronavirus 229E (HCoV-229E) Vero-E6 cell lines as a model for the Coronaviridae family. Fifteen synthetic congeners pointed out miscellaneous antiviral efficacies against HCoV-229E with variable inhibition degrees. Compound 18 showed a high selectivity index (SI = 12.6) that established spectacular inhibitory capacity against human coronavirus 229E. Compounds 6, 7, and 14 exposed moderate efficacies. Compounds 6, 7, 14, and 18 exhibited substantial antiviral action through the replication phase with reduction percentages extending from 53.6%, 60.7%, and 55% to 82.2%, correspondingly. Likewise, when assessed to the positive control tipranavir (88.6%), the inhibitory efficiency of compounds 6, 7, 14, and 18 versus the SARS-CoV2 Mpro provided high percentages of 80.4%, 73.1%, 81.4% and up to 84.5%, respectively. In silico studies were performed to investigate further the biological activity and the target compounds’ physical and chemical features, including molecular dynamic (MD) simulations, protein–ligand docking, ADME studies, and density functional theory (DFT) calculations. These inquiries demonstrated that this series of metabolically stable pyranopyrazoles and their annulated systems are effective human coronavirus inhibitors that inhibit the viral Mpro protein and may have emerged as a novel COVID-19 curative option.

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Design, synthesis, docking, and antiviral evaluation of some novel pyrimidinone-based α-aminophosphonates as potent H1N1 and HCoV-229E inhibitors

Hekal,

Hammad,

El-Brollosy

et al. 2024

Bioorganic Chemistry

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Discovery of novel papain-like protease inhibitors for potential treatment of COVID-19

Cited by 12 publications

References 72 publications

Complexity‐to‐Diversity and Pseudo‐Natural Product Strategies as Powerful Platforms for Deciphering Next‐Generation Therapeutics

Complexity‐to‐Diversity and Pseudo‐Natural Product Strategies as Powerful Platforms for Deciphering Next‐Generation Therapeutics

Discovery of Pyrano[2,3-c]pyrazole Derivatives as Novel Potential Human Coronavirus Inhibitors: Design, Synthesis, In Silico, In Vitro, and ADME Studies

Design, synthesis, docking, and antiviral evaluation of some novel pyrimidinone-based α-aminophosphonates as potent H1N1 and HCoV-229E inhibitors

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