生物信息学
核酸
核糖核酸
计算生物学
冠状病毒科
生物
肽核酸
冠状病毒
病毒学
小分子
肽
化学
作者
Bichismita Sahu,Santosh Kumar Behera,Rudradip Das,Tanay Dalvi,Arnab Chowdhury,Bhaskar Dewangan,Kiran Kalia,Amit Shard
出处
期刊:Current Computer - Aided Drug Design
[Bentham Science]
日期:2022-01-01
卷期号:16
被引量:1
标识
DOI:10.2174/1573409916666200923143935
摘要
The outburst of the novel coronavirus COVID-19, at the end of December 2019 has turned into a pandemic, risking many human lives. The causal agent being SARS-CoV-2, a member of the long-known Coronaviridae family, is a positive-sense single-stranded enveloped virus and closely related to SARS-CoV. It has become the need of the hour to understand the pathophysiology of this disease, so that drugs, vaccines, treatment regimens and plausible therapeutic agents can be produced.In this regard, recent studies uncovered the fact that the viral genome of SARS-CoV-2 encodes non-structural proteins like RNA-dependent RNA polymerase (RdRp) which is an important tool for its transcription and replication process. A large number of nucleic acid-based anti-viral drugs are being repurposed for treating COVID-19 targeting RdRp. Few of them are at the advanced stage of clinical trials, including remdesivir. While performing a detailed investigation of the large set of nucleic acid-based drugs, we were surprised to find that the synthetic nucleic acid backbone has been explored very little or rare.We designed scaffolds derived from peptide nucleic acid (PNA) and subjected them to in- -silico screening systematically. These designed molecules have demonstrated excellent binding towards RdRp. Compound 12 was found to possess a similar binding affinity as remdesivir with comparable pharmacokinetics. However, the in-silico toxicity prediction indicates that compound 12 may be a superior molecule which can be explored further due to its excellent safety-profile with LD50 12,000mg/kg as opposed to remdesivir (LD50 =1000mg/kg).Compound 12 falls in the safe category of class 6. Synthetic feasibility, equipotent binding and very low toxicity of this peptide nucleic acid-derived compound can make it a leading scaffold to design, synthesize and evaluate many similar compounds for the treatment of COVID-19.
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