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Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
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Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Related Experiment Video

Updated: Jun 20, 2025

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SARS-CoV-2 replication and drug discovery.

Farah Nazir1, Arnaud John Kombe Kombe2, Zunera Khalid2

  • 1Center of Disease Immunity and Investigation, College of Medicine, Lishui University, Lishui, 323000, China.

Molecular and Cellular Probes
|July 18, 2024
PubMed
Summary

Drug repurposing offers a rapid approach to combat COVID-19 by inhibiting SARS-CoV-2 replication. This review details molecular mechanisms of repurposed antivirals targeting viral proteases and polymerases for effective COVID-19 therapeutics.

Keywords:
3C-like protease (3CL(pro))COVID-19Drug discoveryDrug repurposingMain protease (M(pro))Protease inhibitorRNA-Dependent RNA-Polymerase (RdRp)SARS-CoV-2

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Area of Science:

  • Virology
  • Pharmacology
  • Drug Discovery

Background:

  • The COVID-19 pandemic caused by SARS-CoV-2 necessitates rapid antiviral drug development.
  • Traditional drug development is lengthy, making drug repurposing an ideal strategy for immediate COVID-19 treatment.
  • SARS-CoV-2 shares molecular similarities with other coronaviruses, supporting the efficacy of repurposed drugs.

Purpose of the Study:

  • To review the molecular mechanisms underlying drug repurposing strategies against SARS-CoV-2.
  • To explore how repurposed drugs inhibit viral replication by targeting key viral proteins.
  • To provide insights for future drug discovery and development of COVID-19 therapeutics.

Main Methods:

  • Literature review focusing on molecular mechanisms of drug repurposing against SARS-CoV-2.
  • Analysis of repurposed drugs targeting SARS-CoV-2 proteases (3CLpro, PLpro) and polymerases (RdRp).
  • Comparison of SARS-CoV-2 inhibition mechanisms with those of SARS-CoV inhibitors.

Main Results:

  • Repurposed drugs like Carmofur, Ebselen, and GRL017 inhibit SARS-CoV-2 proteases.
  • Drugs such as Suramin, Remdesivir, and Favipiravir show potential in inhibiting viral RNA-dependent RNA-polymerase.
  • Agents like Disulfiram, GC376, and Molnupiravir target virus-cell fusion and host replication pathways.

Conclusions:

  • Drug repurposing is a viable strategy to develop rapid COVID-19 treatments.
  • Understanding molecular inhibition mechanisms is crucial for optimizing repurposed antiviral therapies.
  • This review provides a foundation for developing novel therapeutics against SARS-CoV-2 and future viral threats.