Antisense oligonucleotides to therapeutically target SARS-CoV-2 infection

Area of Science:

• Molecular Biology
• Virology
• Drug Discovery

Background:

• The COVID-19 pandemic caused by SARS-CoV-2 remains a global health concern.
• Novel therapeutic strategies are urgently needed to combat SARS-CoV-2 infections.
• Antisense oligonucleotides (ASOs) represent an under-explored therapeutic modality for COVID-19.

Purpose of the Study:

• To design and evaluate antisense oligonucleotides (ASOs) for inhibiting SARS-CoV-2 infection.
• To investigate ASOs targeting the SARS-CoV-2 genome and host cell entry factors (ACE2, TMPRSS2).

Main Methods:

• Screening of 180 ASOs against various regions of the SARS-CoV-2 genome using a specialized bioassay platform.
• Validation of potent antiviral ASOs in vitro.
• Testing ASOs targeting host entry factors ACE2 and TMPRSS2.

Main Results:

• Several ASOs demonstrated potent inhibition of SARS-CoV-2 infection in vitro.
• Validated ASOs maintained activity against SARS-CoV-2 WA1 and B.1.1.7 (alpha) variants.
• Targeting the host entry factor ACE2 with ASOs effectively blocked infection by SARS-CoV-2 variants.

Conclusions:

• ASOs targeting the SARS-CoV-2 genome and host factors show significant therapeutic potential.
• Further research into ASO development for COVID-19 is warranted.
• ASOs offer a promising avenue for novel SARS-CoV-2 therapeutics.