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Synthesis of Dihydrobenzofuro[3,2-b]chromenes as Potential 3CLpro Inhibitors of SARS-CoV-2: A Molecular Docking and Molecular Dynamics Study.
Gorai, Sudip; Junghare, Vivek; Kundu, Kshama; Gharui, Sowmomita; Kumar, Mukesh; Patro, Birija Sankar; Nayak, Sandip K; Hazra, Saugata; Mula, Soumyaditya.
  • Gorai S; Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
  • Junghare V; Homi Bhabha National Institute Anushakti Nagar, Mumbai, 400094, India.
  • Kundu K; Department of Biotechnology, Centre for Nanotechnology, Indian Institute of Technology Roorkee (IITR), Roorkee, Uttarakhand, India.
  • Gharui S; Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
  • Kumar M; Pondicherry University, Puducherry, 605 014, India.
  • Patro BS; Homi Bhabha National Institute Anushakti Nagar, Mumbai, 400094, India.
  • Nayak SK; Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
  • Hazra S; Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
  • Mula S; Homi Bhabha National Institute Anushakti Nagar, Mumbai, 400094, India.
ChemMedChem ; 17(8): e202100782, 2022 04 20.
Статья в английский | MEDLINE | ID: covidwho-1797944
ABSTRACT
The recent emergence of pandemic of coronavirus (COVID-19) caused by SARS-CoV-2 has raised significant global health concerns. More importantly, there is no specific therapeutics currently available to combat against this deadly infection. The enzyme 3-chymotrypsin-like cysteine protease (3CLpro) is known to be essential for viral life cycle as it controls the coronavirus replication. 3CLpro could be a potential drug target as established before in the case of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In the current study, we wanted to explore the potential of fused flavonoids as 3CLpro inhibitors. Fused flavonoids (5a,10a-dihydro-11H-benzofuro[3,2-b]chromene) are unexplored for their potential bioactivities due to their low natural occurrences. Their synthetic congeners are also rare due to unavailability of general synthetic methodology. Here we designed a simple strategy to synthesize 5a,10a-dihydro-11H-benzofuro[3,2-b]chromene skeleton and it's four novel derivatives. Our structural bioinformatics study clearly shows excellent potential of the synthesized compounds in comparison to experimentally validated inhibitor N3. Moreover, in-silico ADMET study displays excellent druggability and extremely low level of toxicity of the synthesized molecules. Further, for better understanding, the molecular dynamic approach was implemented to study the change in dynamicity after the compounds bind to the protein. A detailed investigation through clustering analysis and distance calculation gave us sound comprehensive data about their molecular interaction. In summary, we anticipate that the currently synthesized molecules could not only be a potential set of inhibitors against 3CLpro but also the insights acquired from the current study would be instrumental in further developing novel natural flavonoid based anti-COVID therapeutic spectrums.
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Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: SARS-CoV-2 / COVID-19 Тип исследования: Наблюдательное исследование / Прогностическое исследование Пределы темы: Люди Язык: английский Журнал: ChemMedChem Тематика журнала: Фармакология / Химия Год: 2022 Тип: Статья Аффилированная страна: Cmdc.202100782

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Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: SARS-CoV-2 / COVID-19 Тип исследования: Наблюдательное исследование / Прогностическое исследование Пределы темы: Люди Язык: английский Журнал: ChemMedChem Тематика журнала: Фармакология / Химия Год: 2022 Тип: Статья Аффилированная страна: Cmdc.202100782