Design and In-silico Screening of Peptide Nucleic Acid (PNA) InspiredNovel Pronucleotide Scaffolds Targeting COVID-19 / Bichismita Sahu, Santosh Kumar Behera, Rudradip Das, Tanay Dalvi, Arnab Chowdhury, Bhaskar Dewangan, Kiran Kalia, Amit Shard

Introduction:The outburst of the novel coronavirus COVID-19, at the end of December2019 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 envelopedvirus and closely related to SARS-CoV. It has become the need of the hour to understand the pathophysiologyof this disease, so that drugs, vaccines, treatment regimens and plausible therapeuticagents can be produced. Methods: In this regard, recent studies uncovered the fact that the viral genome of SARS-CoV-2encodes non-structural proteins like RNA-dependent RNA polymerase (RdRp) which is an importanttool for its transcription and replication process. A large number of nucleic acid-based anti-viraldrugs are being repurposed for treating COVID-19 targeting RdRp. Few of them are at the advancedstage of clinical trials, including remdesivir. While performing a detailed investigation ofthe large set of nucleic acid-based drugs, we were surprised to find that the synthetic nucleic acidbackbone has been explored very little or rare. Results: We designed scaffolds derived from peptide nucleic acid (PNA) and subjected them to in--silico screening systematically. These designed molecules have demonstrated excellent binding towardsRdRp. Compound 12 was found to possess a similar binding affinity as remdesivir with comparablepharmacokinetics. However, the in-silico toxicity prediction indicates that compound 12may be a superior molecule which can be explored further due to its excellent safety-profile withLD50 12,000mg/kg as opposed to remdesivir (LD50 =1000mg/kg). Conclusion: Compound 12 falls in the safe category of class 6. Synthetic feasibility, equipotentbinding and very low toxicity of this peptide nucleic acid-derived compound can make it a leadingscaffold to design, synthesize and evaluate many similar compounds for the treatment ofCOVID-19.

Medienart:	E-Artikel

Erscheinungsjahr:	2021
Erschienen:	2021

Enthalten in:	Zur Gesamtaufnahme - volume:18
Enthalten in:	Current computer-aided drug design - 18(2021), 1, Seite 15

Sprache:	Englisch

Beteiligte Personen:	Sahu, Bichismita [VerfasserIn] Behera, Santosh Kumar [VerfasserIn] Das, Rudradip [VerfasserIn] Dalvi, Tanay [VerfasserIn] Chowdhury, Arnab [VerfasserIn] Dewangan, Bhaskar [VerfasserIn] Kalia, Kiran [VerfasserIn] Shard, Amit [VerfasserIn]

Links:	FID Access [lizenzpflichtig]

Umfang:	1 Online-Ressource (15 p)

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PPN (Katalog-ID):	KFL011155930