Abstract
Explicit hindrance and blockade of the viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is considered one of the most promising and efficient approaches for developing highly potent remedies for COVID-19. However, almost all of the reported viral RdRp inhibitors (either repurposed or new antiviral drugs) lack specific selectivity against the novel coronaviral RdRp and still at a beginning phase of advancement. Herein, I discovered and introduce a new pyrazine derivative, (E)-N-(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide (cyanorona-20), as the first potent SARS-CoV-2 RdRp inhibitor with very high selectivity (209- and 45-fold more potent than favipiravir and remdesivir, respectively). This promising selective specific anti-COVID-19 compound is also deemed to be the first distinctive derivative of favipiravir. Cyanorona-20, the unprecedented nucleoside/nucleotide analog, was designed, synthesized, characterized, computationally studied, and biologically evaluated for its anti-COVID-19 actions (through a precise in vitro anti-COVID-19 assay). The results of the biological assay displayed that cyanorona-20 surprisingly exhibited very high and largely significant anti-COVID-19 activities (anti-SARS-CoV-2 EC 50 = 0.45 μM), and, in addition, it could be also a very promising guide and lead compound for the design and synthesis of new anti-SARS-CoV-2 and anti-COVID-19 agents through structural modifications and further computational studies. Further appraisal for the improvement of cyanorona-20 medication is a prerequisite requirement in the coming days. In a word, the ascent of the second member (cyanorona-20 “Corona Antidote”) of the novel and promising class of anti-COVID-19 pyrazine derivatives would drastically make a medical uprising in the pharmacotherapeutic treatment regimens and protocols of the recently-emerged SARS-CoV-2 infection and its accompanying COVID-19.
Keywords: Anti-COVID-19 Compound; Anti-SARS-CoV-2 Activity; Antidote; Arbidol; Coronavirus; Drug Design and Discovery; Favipiravir; Hydroxychloroquine; Pyrazine Nucleoside/Nucleotide Analog; RNA-dependent RNA Polymerase (RdRp); Remdesivir; SARS-CoV-2.
【저자키워드】 Arbidol, coronavirus, Hydroxychloroquine, Remdesivir, Favipiravir, SARS-CoV-2., RNA-dependent RNA polymerase (RdRp), Anti-COVID-19 Compound, Anti-SARS-CoV-2 Activity, Antidote, Drug Design and Discovery, Pyrazine Nucleoside/Nucleotide Analog, 【초록키워드】 COVID-19, SARS-CoV-2, Arbidol, protocol, Hydroxychloroquine, drug design, SARS-COV-2 infection, antiviral drugs, Remdesivir, Favipiravir, drug, in vitro, anti-SARS-CoV-2, RNA, activity, RdRP, RNA-dependent RNA polymerase, Viral RNA, novel, medication, synthesis, nucleotide, Anti-SARS-CoV-2 Activity, Antidote, protocols, biological assay, viral RNA-dependent RNA polymerase, Compound, treatment regimen, nucleoside, advancement, blockade, selective, Coronaviral, derivative, Modification, pyrazine, hindrance, computational studies, RdRp inhibitor, lack, approach, reported, addition, evaluated, exhibited, characterized, SARS-CoV-2 RdRp inhibitor, 【제목키워드】 anti-SARS-CoV-2,