Nucleoside Analogue for the Treatment of SARS-CoV-2

A new coronavirus named SARS-CoV-2 was identified causing pneumonia at the end of 2019 in Wuhan City of China. Compared to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 seems to be less pathogenic and more transmissible. Effective vaccines and drugs for the direct treatment of SARS-CoV-2 infection are urgently needed. Therefore, it is imperative to develop effective vaccines and drugs as soon as possible.

Creative Biolabs provides comprehensive screening and development services of antiviral drug discovery for SARS-CoV-2, including nucleoside analogues, broad-spectrum antiviral agents, protease inhibitors, neutralizing antibodies, etc.

What is Nucleoside Analogue?

As the basic components of RNA and DNA, nucleosides participate in the preservation, replication and transcription of gene information. In terms of anti-microbial infection and cancer treatment, developing nucleoside analogues to mimic natural nucleosides and inhibit the growth of viruses and tumor cells has become an effective clinical therapy. Nucleoside analogues are synthetic nucleosides which contain a nucleic acid analogue and a sugar. Currently, the development and application of nucleoside drugs mainly focus on antiviral and anti-tumor fields.

Antiviral Mechanisms of Nucleoside Analogues

The antiviral mechanisms of nucleoside analogues with different structures vary. Nucleoside analogues could inhibit the activity of the enzyme and blocking the gene replication of virus by working as a competitive inhibitor of DNA/RNA replicase (such as polymerase, transcriptase, reverse transcriptase, etc.). On the other hand, nucleoside analogues are similar enough to natural nucleotides in structures to be incorporated into growing DNA strands. Due to the structural differences, nucleoside analogues block the elongation of the nascent DNA/RNA molecule by serving as chain terminators and thus inhibit virus replication.

Fig.1 Mechanisms of inhibition by nucleoside and nucleotide analogues. (Pruijssers, 2019)

Nucleoside Analogue Discovery for the Treatment of SARS-CoV-2

SARS-CoV-2 is a newly identified coronavirus with a positive-sense, single-stranded RNA. This is the seventh known coronavirus that infects humans after SARS-CoV and MERS-CoV causing respiratory infections. The development of anti-CoV drugs is challenging due to the high viral yields, short replication cycle, homologous / nonhomologous recombination, and high error rates of positive-sense RNA virus genomes replication.

Since its high structural conservation of the binding site, nucleoside analogue presents a low probability of resistance. Furthermore, amino acid sequence conservation of the RNA-dependent RNA polymerase of coronavirus is relative higher than others, which also suggests that nucleoside analogue can be potentially used for the treatment of SARS-CoV-2 infections.

According to the advantages of nucleoside analogue, Creative Biolabs provides comprehensive R&D services of antiviral nucleoside analogues based on multiple action mechanisms. You can directly choose any of the following nucleoside analogues to learn more, or just feel free to contact us and communicate with us about your specific puzzles. Our PhD scientists will offer you professional solutions as soon as possible.

Reference

1. Pruijssers, A.J.; Denison, M.R. Nucleoside analogues for the treatment of coronavirus infections. Current Opinion in Virology. 2019, 35: 57-62.

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