CoViTris2020 and ChloViD2020: a striking new hope in COVID-19 therapy,Molecular Diversity

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CoViTris2020 and ChloViD2020: a striking new hope in COVID-19 therapy
Molecular Diversity ( IF 3.9 ) Pub Date : 2021-01-03 , DOI: 10.1007/s11030-020-10169-0
Amgad M Rabie _{1,

2,

3}

Affiliation

Abstract

Designing anticoronavirus disease 2019 (anti-COVID-19) agents is the primary concern of medicinal chemists/drug designers nowadays. Repurposing of known active compounds against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new effective and time-saving trend in anti-COVID-19 drug discovery. Thorough inhibition of the coronaviral-2 proteins (i.e., multitarget inhibition) is a possible powerful favorable strategy for developing effectively potent drugs for COVID-19. In this new research study, I succeeded to repurpose the two antioxidant polyhydroxy-1,3,4-oxadiazole compounds CoViTris2020 and ChloViD2020 as the first multitarget coronaviral protein blockers with extremely higher potencies (reach about 65 and 304 times, for CoViTris2020, and 20 and 93 times, for ChloViD2020, more potent than remdesivir and favipiravir, respectively). These two 2,5-disubstituted-1,3,4-oxadiazoles were computationally studied (through molecular docking in almost all SARS-CoV-2 proteins) and biologically assessed (through a newly established robust in vitro anti-COVID-19 assay) for their anticoronaviral-2 bioactivities. The data obtained from the docking investigation showed that both ligands promisingly exhibited very strong inhibitory binding affinities with almost all docked enzymes (e.g., they displayed extremely lower binding energies of − 12.00 and − 9.60 kcal/mol, respectively, with the SARS-CoV-2 RNA-dependent RNA polymerase “RdRp”). The results of the biological assay revealed that CoViTris2020 and ChloViD2020 significantly displayed very high anti-COVID-19 activities (anti-SARS-CoV-2 EC₅₀ = 0.31 and 1.01 μM, respectively). Further in vivo/clinical studies for the development of CoViTris2020 and ChloViD2020 as anti-COVID-19 medications are required. In brief, the ascent of CoViTris2020 and ChloViD2020 as the two lead members of the novel family of anti-COVID-19 polyphenolic 2,5-disubstituted-1,3,4-oxadiazole derivatives represents a promising hope in COVID-19 therapy.

Graphic abstract

CoViTris2020 and ChloViD2020 inhibit SARS-CoV-2 life cycle with surprising EC₅₀ values of 0.31 and 1.01 μM, respectively. CoViTris2020 strongly inhibits coronaviral-2 RdRp with exceptionally lower inhibitory binding energy of − 12.00 kcal/mol.

中文翻译：

CoViTris2020 和 ChloViD2020：COVID-19 治疗的惊人新希望

抽象的

设计抗 2019 年冠状病毒病（抗 COVID-19）药物是当今药物化学家/药物设计师首要关注的问题。重新利用已知的抗严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的活性化合物是抗 COVID-19 药物发现中一种有效且节省时间的新趋势。彻底抑制冠状病毒-2 蛋白（即多靶点抑制）可能是开发有效治疗 COVID-19 药物的一种强有力的有利策略。在这项新的研究中，我成功地将两种抗氧化剂多羟基-1,3,4-恶二唑化合物CoViTris2020和ChloViD2020重新利用为第一个具有极高效力的多靶点冠状病毒蛋白阻断剂（ CoViTris2020分别达到约 65 和 304 倍，以及 20对于ChloViD2020 ，分别是 93 倍和 93 倍，分别比瑞德西韦和法匹拉韦更有效）。这两种 2,5-二取代-1,3,4-恶二唑经过计算研究（通过几乎所有 SARS-CoV-2 蛋白的分子对接）和生物学评估（通过新建立的强大的体外抗 COVID-19 测定）因其抗冠状病毒 2 生物活性。从对接研究中获得的数据表明，两种配体有望与几乎所有对接的酶表现出非常强的抑制性结合亲和力（例如，它们与 SARS-CoV-分别表现出极低的结合能 - 12.00 和 - 9.60 kcal/mol） 2 RNA 依赖性 RNA 聚合酶“RdRp”）。生物测定结果显示， CoViTris2020和ChloViD2020显着表现出非常高的抗COVID-19活性（抗SARS-CoV-2 EC ₅₀分别 = 0.31 和 1.01 μM）。需要对CoViTris2020和ChloViD2020作为抗 COVID-19 药物的开发进行进一步的体内/临床研究。简而言之， CoViTris2020和ChloViD2020作为抗 COVID-19 多酚 2,5-二取代-1,3,4-恶二唑衍生物新型家族的两个主要成员的崛起代表了 COVID-19 治疗的光明希望。