Molecular docking, molecular dynamic and drug-likeness studies of natural flavonoids as inhibitors for SARS-CoV-2 main protease (Mpro)

N.A.

Makale detayları

Molecular docking, molecular dynamic and drug-likeness studies of natural flavonoids as inhibitors for SARS-CoV-2 main protease (Mpro)

Yazarlar:

N.A.

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Chemistry

Dergi:

Journal of Research in Pharmacy Vol.25 Issue 6, pp.998-1009

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347531

pISSN:

2630-6344

Anahtar kelimeler:

Özet:

 The emergence of the global pandemic COVID-19 lead to a huge demand for the therapeutic agent to combat the disease. Since the FDA approval of some of HIV-1 main protease inhibitors such as ritonavir lopinavir to treat COVID-19, the investigation of anti-HIV inhibitor to inhibit SARS-CoV-2 main protease Mpro is getting considerably much attention. This study evaluates the potency of sixteen selected natural flavonoids which were previously reported active to block HIV-1 protease as potential inhibitors of SARS-CoV-2 Mpro. The molecular docking and dynamic study were completed to know the binding affinity and stability of the protein-ligand complex via docking study along with molecular dynamic simulations. Moreover, drug-likeness was also evaluated through via ADMET evaluation. This study revealed robinin 6, a flavonol molecule with linked to galactose-rhamnose at C3 and rhamnose molecule at C7, exhibited the highest binding affinity -9 kcalmol among others. The amino acids that interacted with robinin were Asn142; Gly143; Arg188; Thr190. The binding affinity of robinin surpassed the binding affinity of ritonavir -7.7 kcalmol and lopinavir -8.2 kcalmol. The replacement of the hydroxyl group from the flavonoid skeleton at C- 7, C-4 was proposed to affect the binding affinity. The free hydroxyl group particularly in A ring and the position of the hydroxyl group were important to improve the binding affinity. The molecular dynamic simulation showed the stability of Mpro-robinin during the simulation period. The ADME evaluation referring to Lipinskis rule of 5 revealed that the flavonoids 2,5,6,9,10,13,14,15 show low oral bioavailability and absorption. Robinin exhibited a good drug- likeness score value:1 with an unconcerned level of acute toxicity. From this study, it was concluded that robinin showed the most potent natural flavonoids studied to inhibit SASR-CoV-2 Mpro by both docking study and ADMEtox properties evaluation.

 The emergence of the global pandemic COVID-19 lead to a huge demand for the therapeutic agent to combat the disease. Since the FDA approval of some of HIV-1 main protease inhibitors such as ritonavir lopinavir to treat COVID-19, the investigation of anti-HIV inhibitor to inhibit SARS-CoV-2 main protease Mpro is getting considerably much attention. This study evaluates the potency of sixteen selected natural flavonoids which were previously reported active to block HIV-1 protease as potential inhibitors of SARS-CoV-2 Mpro. The molecular docking and dynamic study were completed to know the binding affinity and stability of the protein-ligand complex via docking study along with molecular dynamic simulations. Moreover, drug-likeness was also evaluated through via ADMET evaluation. This study revealed robinin 6, a flavonol molecule with linked to galactose-rhamnose at C3 and rhamnose molecule at C7, exhibited the highest binding affinity -9 kcalmol among others. The amino acids that interacted with robinin were Asn142; Gly143; Arg188; Thr190. The binding affinity of robinin surpassed the binding affinity of ritonavir -7.7 kcalmol and lopinavir -8.2 kcalmol. The replacement of the hydroxyl group from the flavonoid skeleton at C- 7, C-4 was proposed to affect the binding affinity. The free hydroxyl group particularly in A ring and the position of the hydroxyl group were important to improve the binding affinity. The molecular dynamic simulation showed the stability of Mpro-robinin during the simulation period. The ADME evaluation referring to Lipinskis rule of 5 revealed that the flavonoids 2,5,6,9,10,13,14,15 show low oral bioavailability and absorption. Robinin exhibited a good drug- likeness score value:1 with an unconcerned level of acute toxicity. From this study, it was concluded that robinin showed the most potent natural flavonoids studied to inhibit SASR-CoV-2 Mpro by both docking study and ADMEtox properties evaluation.

 The emergence of the global pandemic COVID-19 lead to a huge demand for the therapeutic agent to combat the disease. Since the FDA approval of some of HIV-1 main protease inhibitors such as ritonavir lopinavir to treat COVID-19, the investigation of anti-HIV inhibitor to inhibit SARS-CoV-2 main protease Mpro is getting considerably much attention. This study evaluates the potency of sixteen selected natural flavonoids which were previously reported active to block HIV-1 protease as potential inhibitors of SARS-CoV-2 Mpro. The molecular docking and dynamic study were completed to know the binding affinity and stability of the protein-ligand complex via docking study along with molecular dynamic simulations. Moreover, drug-likeness was also evaluated through via ADMET evaluation. This study revealed robinin 6, a flavonol molecule with linked to galactose-rhamnose at C3 and rhamnose molecule at C7, exhibited the highest binding affinity -9 kcalmol among others. The amino acids that interacted with robinin were Asn142; Gly143; Arg188; Thr190. The binding affinity of robinin surpassed the binding affinity of ritonavir -7.7 kcalmol and lopinavir -8.2 kcalmol. The replacement of the hydroxyl group from the flavonoid skeleton at C- 7, C-4 was proposed to affect the binding affinity. The free hydroxyl group particularly in A ring and the position of the hydroxyl group were important to improve the binding affinity. The molecular dynamic simulation showed the stability of Mpro-robinin during the simulation period. The ADME evaluation referring to Lipinskis rule of 5 revealed that the flavonoids 2,5,6,9,10,13,14,15 show low oral bioavailability and absorption. Robinin exhibited a good drug- likeness score value:1 with an unconcerned level of acute toxicity. From this study, it was concluded that robinin showed the most potent natural flavonoids studied to inhibit SASR-CoV-2 Mpro by both docking study and ADMEtox properties evaluation.

 The emergence of the global pandemic COVID-19 lead to a huge demand for the therapeutic agent to combat the disease. Since the FDA approval of some of HIV-1 main protease inhibitors such as ritonavir lopinavir to treat COVID-19, the investigation of anti-HIV inhibitor to inhibit SARS-CoV-2 main protease Mpro is getting considerably much attention. This study evaluates the potency of sixteen selected natural flavonoids which were previously reported active to block HIV-1 protease as potential inhibitors of SARS-CoV-2 Mpro. The molecular docking and dynamic study were completed to know the binding affinity and stability of the protein-ligand complex via docking study along with molecular dynamic simulations. Moreover, drug-likeness was also evaluated through via ADMET evaluation. This study revealed robinin 6, a flavonol molecule with linked to galactose-rhamnose at C3 and rhamnose molecule at C7, exhibited the highest binding affinity -9 kcalmol among others. The amino acids that interacted with robinin were Asn142; Gly143; Arg188; Thr190. The binding affinity of robinin surpassed the binding affinity of ritonavir -7.7 kcalmol and lopinavir -8.2 kcalmol. The replacement of the hydroxyl group from the flavonoid skeleton at C- 7, C-4 was proposed to affect the binding affinity. The free hydroxyl group particularly in A ring and the position of the hydroxyl group were important to improve the binding affinity. The molecular dynamic simulation showed the stability of Mpro-robinin during the simulation period. The ADME evaluation referring to Lipinskis rule of 5 revealed that the flavonoids 2,5,6,9,10,13,14,15 show low oral bioavailability and absorption. Robinin exhibited a good drug- likeness score value:1 with an unconcerned level of acute toxicity. From this study, it was concluded that robinin showed the most potent natural flavonoids studied to inhibit SASR-CoV-2 Mpro by both docking study and ADMEtox properties evaluation.

Makale detayları

Molecular docking, molecular dynamic and drug-likeness studies of natural flavonoids as inhibitors for SARS-CoV-2 main protease (Mpro)

Yazarlar:

N.A.

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Chemistry

Dergi:

Journal of Research in Pharmacy Vol.25 Issue 6, pp.998-1009

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347531

pISSN:

2630-6344

Anti-viral

COVID-19

Docking

Flavonoids

Mpro

Sayı

Makale detayları

Molecular docking, molecular dynamic and drug-likeness studies of natural flavonoids as inhibitors for SARS-CoV-2 main protease (Mpro)

Yazarlar: N.A.

Yayıncı: Marmara University

Ana Başlıklar: Pharmaceutical Chemistry

Dergi: Journal of Research in Pharmacy Vol.25 Issue 6, pp.998-1009

Belge Tipi: Makale

Yayın Tarihi: 6/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001347531

pISSN: 2630-6344

Anti-viral

COVID-19

Docking

Flavonoids

Mpro

Sayı

Yazarlar:

N.A.

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmaceutical Chemistry

Dergi:

Journal of Research in Pharmacy Vol.25 Issue 6, pp.998-1009

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347531

pISSN:

2630-6344