Commercially Available Flavonols Are Better SARS-CoV-2 Inhibitors than Isoflavone and Flavones.
Commercially Available Flavonols Are Better SARS-CoV-2 Inhibitors than Isoflavone and Flavones.
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市售黄酮醇是比异黄酮和黄酮更好的SARS-CoV-2抑制剂。
DOI：
10.3390/v14071458
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发表时间：
2022-06-30
期刊：
影响因子：
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中科院分区：
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尽管疫苗的快速发展，严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）仍在传播，并产生逃避体液免疫反应的变异体（VoC）。在这种情况下，寻找抗SARS-CoV-2的化合物仍然是必要的。一类被称为类黄酮的天然多酚，经常存在于水果和蔬菜中，被广泛用于治疗不同的疾病，并用作新药设计的支架。因此，在本文中，我们使用基于细胞的测定和经实验酶数据验证的计算机模拟计算，评估了分为三个亚类的七种黄酮类化合物，即染料木黄酮（染料木黄酮）、黄酮（芹菜素和木犀草素）和黄酮醇（非瑟酮、山奈酚、杨梅素和槲皮素），用于COVID-19治疗。黄酮醇是比异黄酮和黄酮更好的SARS-CoV-2抑制剂。黄酮醇山奈酚、槲皮素和杨梅苷的环B中羟基数目的增加降低了50%有效浓度（EC 50）值，这是由于它们对靶内化合物的取向的影响。杨梅素和非瑟酮似乎是优选的候选药物;它们都具有抗炎作用（降低TNF-α水平），并主要通过以非竞争性方式靶向主要蛋白酶（Mpro）的可加工性来抑制SARS-CoV-2，其效力与重新使用的药物阿扎那韦相当。然而，非瑟酮和杨梅苷也可能被认为是适合于合成修饰的命中物，以通过不仅抑制Mpro，而且抑制3′-5′外切核酸酶（ExoN）来改善其抗SARS-CoV-2谱。
Despite the fast development of vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still circulating and generating variants of concern (VoC) that escape the humoral immune response. In this context, the search for anti-SARS-CoV-2 compounds is still essential. A class of natural polyphenols known as flavonoids, frequently available in fruits and vegetables, is widely explored in the treatment of different diseases and used as a scaffold for the design of novel drugs. Therefore, herein we evaluate seven flavonoids divided into three subclasses, isoflavone (genistein), flavone (apigenin and luteolin) and flavonol (fisetin, kaempferol, myricetin, and quercetin), for COVID-19 treatment using cell-based assays and in silico calculations validated with experimental enzymatic data. The flavonols were better SARS-CoV-2 inhibitors than isoflavone and flavones. The increasing number of hydroxyl groups in ring B of the flavonols kaempferol, quercetin, and myricetin decreased the 50% effective concentration (EC50) value due to their impact on the orientation of the compounds inside the target. Myricetin and fisetin appear to be preferred candidates; they are both anti-inflammatory (decreasing TNF-α levels) and inhibit SARS-CoV-2 mainly by targeting the processability of the main protease (Mpro) in a non-competitive manner, with a potency comparable to the repurposed drug atazanavir. However, fisetin and myricetin might also be considered hits that are amenable to synthetic modification to improve their anti-SARS-CoV-2 profile by inhibiting not only Mpro, but also the 3′–5′ exonuclease (ExoN).
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影响因子：
5.6
作者：
Kaul R;Paul P;Kumar S;Büsselberg D;Dwivedi VD;Chaari A
通讯作者：
Chaari A
影响因子：
5.5
作者：
通讯作者：
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DOI：
10.3390/ph14060546
发表时间：
2021-06-07
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Godinho PIC;Soengas RG;Silva VLM
通讯作者：
Silva VLM
影响因子：
11.4
作者：
BEESE, LS;STEITZ, TA
通讯作者：
STEITZ, TA
DOI：
10.1016/j.biopha.2021.111430
发表时间：
2021-06
期刊：
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
影响因子：
--
作者：
Liskova A;Samec M;Koklesova L;Samuel SM;Zhai K;Al-Ishaq RK;Abotaleb M;Nosal V;Kajo K;Ashrafizadeh M;Zarrabi A;Brockmueller A;Shakibaei M;Sabaka P;Mozos I;Ullrich D;Prosecky R;La Rocca G;Caprnda M;Büsselberg D;Rodrigo L;Kruzliak P;Kubatka P
通讯作者：
Kubatka P